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Gonadal hormone regulation of behaviour in the Mongolian gerbil Raible, Lyn Helene 1982

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GONADAL HORMONE REGULATION OF BEHAVIOUR IN THE MONGOLIAN GERBIL by LYN HELENE RAIBLE B.A. San F r a n c i s c o S t a t e U n i v e r s i t y A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF THE FACULTY OF GRADUATE STUDIES Dep a r t m e n t of P s y c h o l o g y We a c c e p t t h i s t h e s i s a s c o n f o r m i n g t o t h e r e q u i r e d s t a n d a r d THE UNIVERSITY OF BRITISH COLUMBIA M a s t e r of A r t s i n A u g u s t , 1982 Ly n H e l e n e R a i b l e In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the requirements f o r an advanced degree a t the U n i v e r s i t y of B r i t i s h Columbia, I agree t h a t the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and study. I f u r t h e r agree t h a t p e r m i s s i o n f o r e x t e n s i v e copying o f t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the head o f my department or by h i s or her r e p r e s e n t a t i v e s . I t i s understood t h a t copying or p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be allowed without my w r i t t e n p e r m i s s i o n . Department of p6^^0LOG>y The U n i v e r s i t y o f B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 Date /^/J^U^6 /7 /?$2 DE-6 (.3/81) i i ABSTRACT G o n a d a l s t e r o i d s have been f o u n d t o i n f l u e n c e a v a r i e t y o f b e h a v i o u r s i n mammals. However, many o f t h e models and h y p o t h e s e s c o n c e r n i n g t h e o r g a n i z a t i o n a l and a c t i v a t i o n a l e f f e c t s of g o n a d a l s t e r o i d s a r e b a s e d on d a t a o b t a i n e d p r i m a r i l y f r o m t h e r a t . E x a m i n a t i o n o f t h e e f f e c t s o f g o n a d a l s t e r o i d s on b e h a v i o u r i n r o d e n t s p e c i e s w h i c h d i f f e r f r o m t h e r a t i n t h e i r e c o l o g i c a l n i c h e w o u l d a i d i n d e t e r m i n i n g t h e g e n e r a l i t y of s u c h h y p o t h e s e s and m o d e l s . The M o n g o l i a n g e r b i l , a r e l a t i v e l y new l a b o r a t o r y a n i m a l , i n h a b i t s an e n v i r o n m e n t q u i t e d i f f e r e n t f r o m t h a t of t h e r a t and c o u l d p r o v i d e u s e f u l c o m p a r a t i v e d a t a . The g e n e r a l p u r p o s e of t h e p r e s e n t s t u d y was t o examine t h e e f f e c t s of g o n a d a l s t e r o i d s on f e e d i n g and s e x u a l b e h a v i o u r i n t h e f e m a l e g e r b i l . In a d d i t i o n , t h e h y p o t h e s i s t h a t t h e e x t e n t of p e r i n a t a l a n d r o g e n - i n d u c e d d e f e m i n i z a t i o n c a n be u s e d t o p r e d i c t whether a n d r o g e n s o r e s t r o g e n s w i l l be t h e p r i m a r y r e g u l a t o r f o o d i n t a k e and body w e i g h t i n a d u l t h o o d (and v i c e v e r s a ) was t e s t e d . In t h e f i r s t s e r i e s o f e x p e r i m e n t s , i t was f o u n d t h a t , i n t h e f e m a l e g e r b i l , a s i n o t h e r f e m a l e r o d e n t s , o v a r i a n s t e r o i d s a r e p r i m a r y r e g u l a t o r s o f s e x u a l r e c e p t i v i t y . When compared t o o t h e r f e m a l e r o d e n t s , t h e s y s t e m r e g u l a t i n g r e c e p t i v i t y i n t h e g e r b i l a p p e a r e d t o be l e s s s e n s i t i v e t o e s t r o g e n as w e l l a s more d e p e n d e n t on t h e s y n e r g i s t i c a c t i o n of p r o g e s t e r o n e w i t h e s t r o g e n f o r t h e i n d u c t i o n o f r e c e p t i v i t y . The s e c o n d s e r i e s o f e x p e r i m e n t s i n d i c a t e d t h a t a d r e n a l e c t o m y s i g n i f i c a n t l y d e c r e a s e d s e x u a l r e c e p t i v i t y i n t h e f e m a l e g e r b i l , an e f f e c t not o b s e r v e d i n o t h e r r o d e n t s . F u r t h e r e x a m i n a t i o n o f t h i s e f f e c t s u g g e s t e d t h a t a d r e n a l s t e r o i d s , i n a d d i t i o n t o o v a r i a n s t e r o i d s , were e s s e n t i a l f o r t h e e l i c i t a t i o n o f h i g h l e v e l s of r e c e p t i v i t y . However, a l t h o u g h p a r t i c u l a r c o m b i n a t i o n s of a d r e n a l s t e r o i d s d i d r e s t o r e n o r m a l r e s p o n d i n g i n a n i m a l s t e s t e d w i t h e s t r o g e n a l o n e , t h e y f a i l e d t o e l i m i n a t e t h e d e c r e a s e d r e c e p t i v i t y o b s e r v e d when e s t r o g e n and p r o g e s t e r o n e were a d m i n i s t e r e d . Thus, i n t h e g e r b i l , u n l i k e o t h e r r o d e n t s , a d r e n a l e c t o m y a p p e a r s t o d e c r e a s e t h e s e n s i t i v i t y o f t h e s y s t e m r e g u l a t i n g r e c e p t i v i t y t o p r o g e s t e r o n e . The e f f e c t s o f o v a r i a n s t e r o i d s on f o o d i n t a k e and body w e i g h t i n male and f e m a l e g e r b i l s were examined i n t h e t h i r d s e t o f e x p e r i m e n t s . I t was f o u n d t h a t , i n t h e g e r b i l , as i n most o t h e r r o d e n t s , o v a r i a n s t e r o i d s a p p e a r e d t o be t h e p r i m a r y h o r m o n a l r e g u l a t o r s of f o o d i n t a k e and body w e i g h t . However, u n l i k e e f f e c t s o b s e r v e d i n o t h e r r o d e n t s , o v a r i a n s t e r o i d s were not f o u n d t o be r e s p o n s i b l e f o r t h e sex d i f f e r e n c e i n f o o d i n t a k e and body w e i g h t , i n d i c a t i n g t h e i n v o l v e m e n t of a non-h o r m o n a l f a c t o r . I t was a l s o s u g g e s t e d t h a t i n t e r s p e c i f i c d i f f e r e n c e s i n h o r m o n e - n e u r o t r a n s m i t t e r i n t e r a c t i o n s m ight be r e s p o n s i b l e f o r t h e d i f f e r e n c e s i n t h e h o r m o n a l e f f e c t s on f o o d i n t a k e and body w e i g h t . The f i n d i n g s t h a t o v a r i a n s t e r o i d s were t h e p r i m e h o r m o n a l r e g u l a t o r s o f f o o d i n t a k e a n d body w e i g h t i n t h e g e r b i l l e d t o t h e p r e d i c t i o n t h a t p e r i n a t a l a n d r o g e n s would d e f e m i n i z e t h e g e r b i l . At p r e s e n t , o n l y r o d e n t s i n w h i c h o v a r i a n s t e r o i d s e x e r t t h e p r i m a r y h o r m o n a l i n f l u e n c e on f o o d i n t a k e and body w e i g h t a r e d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s . The f i n a l s e t of i v e x p e r i m e n t s i n d i c a t e d t h a t , l i k e o t h e r s u c h r o d e n t s , t h e g e r b i l was a l s o d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s . In c o n t r a s t t o e f f e c t s i n t h e r a t , none o f t h e e x p e r i m e n t a l t r e a t m e n t s r e s u l t e d i n b e h a v i o u r a l m a s c u l i n i z a t i o n a l t h o u g h s i g n i f i c a n t p h y s i o l o g i c a l m a s c u l i n i z a t i o n was o b s e r v e d . The a b i l i t y of p r e s e n t m o d els of t h e d i f f e r e n t i a t i o n p r o c e s s t o a c c o u n t f o r t h e s e r e s u l t s was examined and a more g e n e r a l c o n c e p t p r o p o s e d . The c o n c e p t p r o p o s e d a l s o p r o v i d e s a p o s s i b l e l i n k between i n t e r s p e c i f i c d i f f e r e n c e s i n t h e d i f f e r e n t i a t i o n of s e x u a l b e h a v i o u r and t h e d i f f e r e n t i a t i o n of o t h e r h o r m o n a l l y m e d i a t e d b e h a v i o u r s . The r e s u l t s of t h e p r e s e n t s t u d y i n d i c a t e t h a t t h e o r g a n i z a t i o n and a c t i v a t i o n a l e f f e c t s of sex s t e r o i d s i n t h e M o n g o l i a n g e r b i l a r e u n i q u e i n s e v e r a l r e s p e c t s and t h a t f u r t h e r i n v e s t i g a t i o n s h o u l d a i d i n d e v e l o p i n g and r e f i n i n g p r e s e n t m odels of t h e h o r m o n a l r e g u l a t i o n o f d e v e l o p m e n t and b e h a v i o u r . V TABLE OF CONTENTS ABSTRACT i i L I S T OF TABLES v i i L I S T OF FIGURES v i i i ACKNOWLEDGEMENTS x INTRODUCTION ..1 SECTION l a - Dose and T e m p o r a l P a r a m e t e r s of O v a r i a n S t e r o i d E f f e c t s on S e x u a l R e c e p t i v i t y 12 G e n e r a l Methods 13 E x p e r i m e n t 1 ....15 E x p e r i m e n t 2 19 E x p e r i m e n t 3 22 E x p e r i m e n t 4 23 G e n e r a l D i s c u s s i o n 29 SECTION I b - E f f e c t s o f H o u s i n g C o n d i t i o n , A d r e n a l S t e r o i d s , and Hormone Dose on S e x u a l R e c e p t i v i t y 33 G e n e r a l Methods • 35 E x p e r i m e n t 5 ...35 E x p e r i m e n t 6 41 E x p e r i m e n t 7 46 E x p e r i m e n t 8 53 G e n e r a l D i s c u s s i o n 59 SECTION I I - Hormonal R e g u l a t i o n and S e x u a l D i f f e r e n t i a t i o n o f Food I n t a k e Mechanisms and M a t i n g A c t i v i t y 65 I l a - Fo o d I n t a k e , Body W e i g h t , and L o r d o s i s 69 G e n e r a l Methods 71 E x p e r i m e n t 9 74 E x p e r i m e n t 10 83 V I G e n e r a l D i s c u s s i o n 92 l i b - P r e - and N e o n a t a l T e s t o s t e r o n e P r o p i o n a t e E x p o s u r e : E f f e c t s on Male and Female S e x u a l B e h a v i o u r i n A d u l t h o o d 101 G e n e r a l Methods 115 E x p e r i m e n t 11 116 E x p e r i m e n t 12 128 G e n e r a l D i s c u s s i o n 142 SECTION I I I - Summary and C o n c l u s i o n s 151 v i i L I S T OF TABLES 1. Mean f o o d i n t a k e and body w e i g h t i n f e m a l e g e r b i l s as a f u n c t i o n of o v a r i e c t o m y and o v a r i a n s t e r o i d t r e a t m e n t : 81 2. Mean f o o d i n t a k e and body w e i g h t i n male g e r b i l s a s a f u n c t i o n o f c a s t r a t i o n and o v a r i a n s t e r o i d t r e a t m e n t 91 3. M a l e s e x u a l b e h a v i o u r i n i n t a c t male g e r b i l s and i n f e m a l e g e r b i l s t r e a t e d n e o n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e 120 4. Male s e x u a l b e h a v i o u r i n c a s t r a t e d male g e r b i l s and i n o v a r i e c t o m i z e d f e m a l e g e r b i l s t r e a t e d n e o n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e 121 4a. A d d i t i o n a l measures o f s e x u a l b e h a v i o u r f o r T4 d a t a o f T a b l e 4 122 5. F e male s e x u a l b e h a v i o u r i n c a s t r a t e d male g e r b i l s and i n o v a r i e c t o m i z e d f e m a l e g e r b i l s t r e a t e d n e o n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e and a d m i n i s t e r e d o v a r i a n s t e r o i d s i n a d u l t h o o d .....123 6. Male s e x u a l b e h a v i o u r i n i n t a c t male g e r b i l s e x p o s e d t o v e h i c l e i n j e c t i o n s p e r i n a t a l l y 131 7. M a l e s e x u a l b e h a v i o u r i n c a s t r a t e d male g e r b i l s e x p o s e d t o p e r i n a t a l v e h i c l e i n j e c t i o n s 133 7a. A d d i t i o n a l measures o f s e x u a l b e h a v i o u r f o r T4 d a t a o f T a b l e 7 134 8. Female s e x u a l b e h a v i o u r i n o v a r i e c t o m i z e d f e m a l e g e r b i l s e x p o s e d t o p e r i n a t a l v e h i c l e i n j e c t i o n s 135 9. C o m p a r i s o n of i n d i c e s o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n u n t r e a t e d male and f e m a l e g e r b i l s , male and f e m a l e g e r b i l s e x p o s e d t o v e h i c l e i n j e c t i o n s p e r i n a t a l l y , and f e m a l e g e r b i l s e x p o s e d t o t e s t o s t e r o n e p r o p i o n a t e p e r i n a t a l l y 139 v i i i L I S T OF FIGURES 1. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s a t v a r i o u s t i m e s a f t e r p r o g e s t e r o n e t r e a t m e n t 18 2. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s d o s e s o f p r o g e s t e r o n e 21 3. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s d o s e s o f e s t r o g e n 25 4. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s t e s t e d d a i l y and c h r o n i c a l l y a d m i n i s t e r e d v a r i o u s d o s e s o f e s t r o g e n 28 5. E f f e c t s o f a d r e n a l e c t o m y , h o u s i n g c o n d i t i o n , and dose of c h r o n i c a l l y a d m i n i s t e r e d e s t r o g e n on s e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s 39 6. S e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a I e c t o m i z e d f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s d o s e s o f p r o g e s t e r o n e 44 7. S e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d f e m a l e g e r b i l s a d m i n i s t e r e d a d r e n a l s t e r o i d s 51 8. S e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s c o m b i n a t i o n s of a d r e n a l s t e r o i d s 56 9. E f f e c t s o f o v a r i e c t o m y and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n f e m a l e g e r b i l s 77 10. E f f e c t s o f o v a r i e c t o m y and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n f e m a l e g e r b i l s r e l a t i v e t o l e v e l s e x h i b i t e d by i n t a c t c o n t r o l a n i m a l s 80 11. E f f e c t s o f c a s t r a t i o n and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n male g e r b i l s 87 12. E f f e c t s o f c a s t r a t i o n and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n male g e r b i l s r e l a t i v e t o l e v e l s e x h i b i t e d by i n t a c t c o n t r o l a n i m a l s 89 13. C o m p a r i s o n of i n d i c e s of p h y s i o l o g i c a l m a s a c u l i n i z a t i o n i n male g e r b i l s and i n f e m a l e g e r b i l s r e c e i v i n g a s i n g l e n e o n a t a l i n j e c t i o n of t e s t o s t e r o n e p r o p i o n a t e 14. C o m p a r i s o n o f i n d i c e s o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n f e m a l e g e r b i l s t r e a t e d p e r i n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e 15. M o d e l s o f s e x u a l d i f f e r e n t i a t i o n . X ACKNOWLEDGEMENTS I would l i k e t o thank my s u p e r v i s o r , Dr. B.B. G o r z a l k a , f o r h i s s u p p o r t , a s s i s t a n c e and enc o u r a g e m e n t , f o r not s a y i n g "I t o l d y o u s o " t o o many t i m e s , and f o r m a i n t a i n i n g h i s s e n s e of humour t h r o u g h o u t my t e n u r e a s a M a s t e r ' s s t u d e n t . I would a l s o l i k e t o t h a n k c o m m i t t e e members D r . R. Wong and D r . M. B u l l o c k f o r t h e i r s u p p o r t and s u g g e s t i o n s . In a d d i t i o n , I would l i k e t o a c k n o w l e d g e t h e c o n t r i b u t i o n s o f s e v e r a l o t h e r p e o p l e t o t h e p r e s e n t t h e s i s : Sandy K l e i n f e l d f o r h e r t e c h n i c a l a s s i s t a n c e , p e r s o n a l s u p p o r t , and a l l a r o u n d n i c e n e s s , George "H.B." R e n f r e y f o r h i s p e r s o n a l and e m o t i o n a l s u p p o r t , t y p i n g a s s i s t a n c e , l i s t e n i n g a b i l i t y , and p r o f o u n d c a p a c i t y t o u n d e r s t a n d , and D r . L.M. Ward f o r s u p p o r t and s u g g e s t i o n s . T h i s r e s e a r c h was s u p p o r t e d by a N a t u r a l S c i e n c e s and E n g i n e e r i n g R e s e a r c h C o u n c i l o f Canada o p e r a t i n g g r a n t and a U n i v e r s i t y o f B r i t i s h C o l u m b i a o p e r a t i n g g r a n t h e l d by D r . B.B. G o r z a l k a . 1 INTRODUCTION G o n a d a l s t e r o i d s have been f o u n d t o i n f l u e n c e a l a r g e number of b e h a v i o u r s i n v e r t e b r a t e s . Not o n l y do t h e y d e t e r m i n e t h e m o r p h o l o g y o f t h e e x t e r n a l g e n i t a l i a , t h e y a l s o i n f l u e n c e c o g n i t i v e a b i l i t i e s , f o o d c o n s u m p t i o n , a g g r e s s i o n , and a v a r i e t y o f o t h e r b e h a v i o u r s n o t d i r e c t l y a s s o c i a t e d w i t h s e x u a l b e h a v i o u r . I t i s now g e n e r a l l y a c c e p t e d t h a t g o n a d a l s t e r o i d s , t h e s o -c a l l e d sex hormones, e x e r t two t y p e s o f e f f e c t , d e p e n d i n g on t h e d e v e l o p m e n t a l s t a g e of t h e a n i m a l . D u r i n g p r e n a t a l d e v e l o p m e n t and, i n some s p e c i e s , e a r l y p o s t n a t a l l i f e , sex hormones e x e r t an o r g a n i z i n g e f f e c t on hormone s e n s i t i v e t i s s u e s . T h i s a c t i o n i s r e s p o n s i b l e f o r t h e m o r p h o l o g y o f t h e e x t e r n a l g e n i t a l i a , c h a n g e s i n n e u r o n a l o r g a n i z a t i o n , and t h e s e n s i t i v i t y o f v a r i o u s t i s s u e s t o s p e c i f i c g o n a d a l s t e r o i d s . The a c t i v a t i o n a l e f f e c t s o f sex s t e r o i d s a r e most a p p a r e n t a t t h e t i m e o f s e x u a l m a t u r i t y , when hormone l e v e l s r i s e and l e a d t o f u r t h e r c h a n g e s i n body m o r p h o l o g y and b e h a v i o u r . F o r example, i n c r e a s e d s e x u a l a c t i v i t y , menarche, t h e d e v e l o p m e n t o f p u b i c , a x i l l a r y , and f a c i a l h a i r , and t h e d e e p e n i n g o f t h e male v o i c e a r e a l l a t t r i b u t a b l e t o t h e a c t i v a t i o n a l e f f e c t s o f g o n a d a l s t e r o i d s . The e f f e c t s o f sex hormones a r e a l s o o b s e r v e d i n a v a r i e t y o f b e h a v i o u r s a l t h o u g h , i n t h e human, t h e s e e f f e c t s a r e not n e a r l y a s o b v i o u s as t h e y a r e i n o t h e r s p e c i e s . One o f t h e major c o n f o u n d s i n d e t e r m i n i n g t h e e f f e c t s of sex s t e r o i d s on human b e h a v i o u r a r i s e s from t h e d i f f i c u l t y i n s e p a r a t i n g c u l t u r a l f r o m b i o l o g i c a l i n f l u e n c e s . Money & E h r h a r d t (1972) 2 f o u n d t h a t c u l t u r a l and s o c i a l i n f l u e n c e s d u r i n g d e v e l o p m e n t were more i m p o r t a n t t h a n g e n e t i c c o n s t i t u t i o n o r p a r t i c u l a r hormones i n d e t e r m i n i n g p s y c h o s e x u a l d e v e l o p m e n t and g e n d e r i d e n t i t y . T h a t i s , t h e sex o f a s s i g n m e n t and r e a r i n g c a n o v e r r i d e b i o l o g i c a l d e t e r m i n a n t s . N o n e t h e l e s s , E h r h a r d t and c o w o r k e r s (1967, 1968) have f o u n d t h a t f e m a l e s e x p o s e d t o a n d r o g e n s p r e n a t a l l y e x h i b i t t o y p r e f e r e n c e s , f a n t a s y c o n t e n t s , and c e r t a i n c o g n i t i v e a b i l i t i e s t h a t r e s e m b l e t h o s e seen i n m a l e s . However, t h e e v i d e n c e i s f a r from c o n v i n c i n g and many a r g u e t h a t t h e d i f f e r e n c e s a r e due t o b i a s e d r e a r i n g r a t h e r t h a n , o r i n a d d i t i o n t o , any i n n a t e sex d i f f e r e n c e ( C a r l s o n , 1980, pp. 3 3 4 ) . I t i s d o u b t f u l t h a t t h e s t u d y o f humans a l o n e w i l l e v e r p r o v i d e s u f f i c i e n t i n f o r m a t i o n t o a l l o w t h e s e p a r a t i o n of c u l t u r a l and b i o l o g i c a l c o n t r i b u t i o n s t o human b e h a v i o u r . In o r d e r t o i n v e s t i g a t e t h e i n f l u e n c e of hormones on s e x u a l d i f f e r e n t i a t i o n and b e h a v i o u r i n t h e a b s e n c e o f s t r o n g c u l t u r a l i n f l u e n c e s , r e s e a r c h e r s have t u r n e d t o non-human a n i m a l s . I n d e e d , t h e use of non-human p r i m a t e s has p r o v i d e d e v i d e n c e t h a t a t l e a s t some of t h e sex d i f f e r e n c e s i n p l a y b e h a v i o u r , s u c h as amount o f r o u g h and tumble p l a y , a r e i n f l u e n c e d by e a r l y h o r m o n a l e n v i r o n m e n t (Goy, 1968, 1970; P h o e n i x , 1974). However, t h e p r i m a t e , a l t h o u g h most s i m i l a r t o t h e human i n many r e s p e c t s , i s n o t o f t e n u s e d f o r r e s e a r c h on t h e more b a s i c o r g a n i z a t i o n a l and a c t i v a t i o n a l e f f e c t s o f sex s t e r o i d s . The h i g h l y d e v e l o p e d and i n t e l l i g e n t n a t u r e o f t h e non-human p r i m a t e r a i s e s e t h i c a l q u e s t i o n s c o n c e r n i n g i t s use as a r e s e a r c h a n i m a l i n s t u d i e s t h a t do n o t r e q u i r e t h e s e c h a r a c t e r i s t i c s . F u r t h e r m o r e , p r i m a t e r e s e a r c h c o s t s a r e b ecoming i n c r e a s i n g l y 3 more p r o h i b i t i v e a s t h e a v i a l a b i l i t y of p r i m a t e s f o r r e s e a r c h c o n t i n u e s t o d e c l i n e . On t h e o t h e r hand, t h e l a b o r a t o r y r o d e n t p o s s e s e s a l l o f t h e e s s e n t i a l f e a t u r e s r e q u i r e d f o r r e s e a r c h i n t o t h e f u n d a m e n t a l a s p e c t s o f t h e h o r m o n a l r e g u l a t i o n of d i f f e r e n t i a t i o n and b e h a v i o u r . Thus, many r e s e a r c h e r s have t u r n e d t o t h e l a b o r a t o r y r o d e n t w i t h t h e aim o f d e v e l o p i n g models of t h e i n f l u e n c e o f hormones on b e h a v i o u r and d e v e l o p m e n t . I t i s from r e s e a r c h s u c h as t h i s t h a t most o f our p r e s e n t knowledge of hor m o n a l i n f l u e n c e s i s d e r i v e d . I n v e s t i g a t i o n s i n t h e l a b o r a t o r y r o d e n t have i n d i c a t e d t h a t t h e o r g a n i z i n g a c t i o n s of a n d r o g e n s d u r i n g s e x u a l d i f f e r e n t i a t i o n a r e r e s p o n s i b l e f o r a g r e a t many sex d i f f e r e n c e s i n b e h a v i o u r o b s e r v e d i n a d u l t h o o d . One o f t h e most o b v i o u s s e x u a l l y d i m o r p h i c b e h a v i o u r s i s s e x u a l b e h a v i o u r i t s e l f . In t h e f e m a l e r o d e n t , s e x u a l b e h a v i o u r i s d e t e r m i n e d p r i m a r i l y by t h e c i r c u l a t i n g l e v e l s o f t h e o v a r i a n s t e r o i d s e s t r o g e n and p r o g e s t e r o n e . In most l a b o r a t o r y r o d e n t s , t h e e s t r o u s c y c l e i s f o u r t o f i v e d a y s i n l e n g t h w i t h e s t r u s , t h e p e r i o d o f r e c e p t i v i t y , l a s t i n g s l i g h t l y under one day. Low l e v e l s of e s t r o g e n and p r o g e s t e r o n e c h a r a c t e r i z e n o n - r e c e p t i v e p e r i o d s , o r d i e s t r u s , w h i l e i n c r e a s i n g e s t r o g e n l e v e l s p l u s a p r o g e s t e r o n e s u r g e b r i n g a b o u t e s t r u s ( K o m i s a r u k , 1978). The c y c l i c n a t u r e of e s t r o g e n and p r o g e s t e r o n e s e c r e t i o n r e f l e c t s t h e c y c l i c n a t u r e of h y p o t h a l a m i c , and t h u s p i t u i t a r y , hormone r e l e a s e . U n d e r . e x p e r i m e n t a l c o n d i t i o n s , a r t i f i c i a l e s t r u s c a n be i n d u c e d by t h e a d m i n i s t r a t i o n o f e s t r a d i o l b e n z o a t e (EB) and p r o g e s t e r o n e (P) i n t h e p r o p e r dose and t e m p o r a l p a t t e r n . S e x u a l b e h a v i o u r i n t h e male r o d e n t , on t h e o t h e r hand, i s 4 d e p e n d e n t upon c i r c u l a t i n g a n d r o g e n s . In male r o d e n t s , t h e r e l e a s e of h y p o t h a l a m i c and p i t u i t a r y hormones i s t o n i c r a t h e r t h a n c y c l i c and t h e s e c r e t i o n of a n d r o g e n s i s r e l a t i v e l y c o n s t a n t . C a s t r a t i o n , w h i c h removes t h e m a j o r s o u r c e o f endogenous a n d r o g e n s , r e s u l t s i n a l o s s of s e x u a l a c t i v i t y w h i l e i n j e c t i o n s of t e s t o s t e r o n e p r o p i o n a t e (TP) r e s t o r e s e x u a l a c t i v i t y . F e m a l e s g i v e n a n d r o g e n s a r o u n d t h e t i m e o f b i r t h f a i l t o e x h i b i t c y c l i c r e l e a s e of p i t u i t a r y hormones and m a l e s c a s t r a t e d a t b i r t h w i l l , u n der a p p r o p r i a t e c o n d i t i o n s , e x h i b i t t h e c y c l i c p a t t e r n of hormone r e l e a s e . T h i s i n d i c a t e s t h a t p e r i n a t a l a n d r o g e n s , r a t h e r t h a n any s t r i c t l y g e n e t i c f a c t o r , a r e r e s p o n s i b l e f o r t h e t o n i c hormone r e l e a s e o b s e r v e d i n t h e male w h i l e t h e a b s e n c e of p e r i n a t a l a n d r o g e n s p e r m i t s t h e c y c l i c p a t t e r n o f hormone r e l e a s e o b s e r v e d i n t h e f e m a l e . The same g e n e r a l i z a t i o n s c a n be made ab o u t t h e o r g a n i z a t i o n a l e f f e c t s o f a n d r o g e n s on a v a r i e t y o f b e h a v i o u r s and c a n be summarized as f o l l o w s : In t h o s e b e h a v i o u r s w h i c h a r e i n f l u e n c e d by t h e o r g a n i z a t i o n a l a c t i o n o f a n d r o g e n s , t h e p r e s e n c e o f a n d r o g e n s d u r i n g t h e p e r i o d o f s e x u a l d i f f e r e n t i a t i o n w i l l p r o d u c e r e s p o n s e s t o sex s t e r o i d s i n a d u l t h o o d t h a t a r e t y p i c a l o f t h e male w h i l e t h e a b s e n c e o f a n d r o g e n s d u r i n g t h i s p e r i o d w i l l p r o d u c e r e s p o n s e s i n a d u l t h o o d t h a t a r e t y p i c a l o f t h e f e m a l e . T h i s much i s c o n s i s t e n t i n a l l r o d e n t s s t u d i e d t o d a t e and t h e r e seems l i t t l e c o n t r o v e r s y a b o u t t h e m a t t e r . Most o f t h e g e n e r a l i z a t i o n s a b o u t t h e e f f e c t s o f p e r i n a t a l a n d r o g e n s on b e h a v i o u r a r e b a s e d on s t u d i e s done i n t h e r a t . T h i s has l e d t o a t e n d e n c y t o o v e r g e n e r a l i z e . F o r example, many 5 r e s e a r c h e r s r e f e r t o t h e d e f e m i n i z i n g a c t i o n of p e r i n a t a l a n d r o g e n s , i m p l y i n g t h a t t h i s i s a n e c e s s a r y c o n s e q u e n c e o f p e r i n a t a l a n d r o g e n e x p o s u r e i n f e m a l e r o d e n t s . The h a m s t e r , w h i c h i s not d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s , p r o v i d e s a c l e a r d e m o n s t r a t i o n t h a t t h e end r e s u l t of t h e o r g a n i z a t i o n a l a c t i o n o f a n d r o g e n s i s n o t n e c e s s a r i l y i d e n t i c a l i n a l l s p e c i e s . I t i s somewhat s u r p r i s i n g t h e n t h a t t h e ha m s t e r f r e q u e n t l y r e c e i v e s l i t t l e more t h a n a p a r a g r a p h i n p a p e r s d e a l i n g w i t h t h e o r g a n i z a t i o n a l e f f e c t s o f a n d r o g e n s . F o r example, P l a p i n g e r & McEwen (1978) d e v o t e one p a r a g r a p h t o t h e h a m s t e r out o f e i g h t p ages on a n d r o g e n ' s e f f e c t s on s e x u a l d i f f e r e n t i a t i o n o f b e h a v i o u r p a t t e r n s i n r o d e n t s and m e r e l y i n f o r m t h e r e a d e r t h a t t h e h a m s t e r i s d i f f e r e n t . The h a m s t e r i s not even m e n t i o n e d i n Ward's (1974) o t h e r w i s e c o m p r e h e n s i v e c h a p t e r on t h e d i f f e r e n t i a t i o n o f s e x u a l b e h a v i o u r . S u r e l y t h e h a m s t e r , d i f f e r i n g from o t h e r r o d e n t s , c o u l d p r o v i d e some i m p o r t a n t c o m p a r a t i v e i n f o r m a t i o n t h a t w o u l d i n c r e a s e our u n d e r s t a n d i n g o f t h e h o r m o n a l m e d i a t i o n of b e h a v i o u r . Y e t t h e r e seems t o be a p e r v a s i v e t e n d e n c y i n t h e l i t e r a t u r e on h o r m o n a l i n f l u e n c e s i n r o d e n t s t o i g n o r e o r d i s m i s s w i t h o u t comment t h e r e s u l t s o b t a i n e d i n t h e h a m s t e r . A l t h o u g h n e v e r o v e r t l y s t a t e d , t h e g e n e r a l i m p r e s s i o n one g e t s i s t h a t b e c a u s e t h e r a t , mouse, and g u i n e a p i g a r e so s i m i l a r i n many r e s p e c t s , t h e y c o m p r i s e t h e norm w h i l e t h e h a m s t e r , b e i n g o v e r t l y d i f f e r e n t , i s a b n o r m a l . C l e a r l y , t h e r a t has become t h e c o m p a r i s o n s p e c i e s , p r o b a b l y b e c a u s e i t i s u s e d f a r more o f t e n t h a n any o t h e r r o d e n t f o r h o r m o n a l r e s e a r c h . T h e r e i s n o t h i n g wrong w i t h u s i n g t h e r a t as a s t a n d a r d f o r c o m p a r i s o n . However, r e s e a r c h e r s t e n d t o f o r g e t 6 that the l a b o r a t o r y r a t ( c l a s s i f i e d as Rattus a l b i n u s by Lockard, 1968) i s as domesticated as the dog and i s about as comparable to a w i l d r a t (R. norvegicus) as a dog i s to a wolf. A f t e r about a century of s e l e c t i v e breeding, the common l a b o r a t o r y r a t e x h i b i t s many d i f f e r e n c e s when compared with the w i l d r a t . For example, i n the l a b o r a t o r y r a t , body l e n g t h and weight are g r e a t e r , the p i t u i t a r y , thymus, t h y r o i d , and p a r a t h y r o i d are l a r g e r while the b r a i n , h e a r t , spleen, a d r e n a l s , l i v e r , and kidneys are smaller than i n the w i l d r a t (Lockard, 1968). Furthermore, the l a b o r a t o r y r a t e x h i b i t s l e s s a g g r e s s i o n and d i f f e r e n t s o c i a l , maternal, and feed i n g behaviours when compared to the w i l d r a t (Lockard, 1968). Given these d i f f e r e n c e s , the experimental f i n d i n g s i n the l a b o r a t o r y r a t should not be taken as n e c e s s a r i l y i n d i c a t i v e of behaviour i n the w i l d r a t , much l e s s the behaviour of other rodents. The unfortunate tendency of some r e s e a r c h e r s to view the hamster as an exception among rodents can r e s u l t i n concepts, t h e o r i e s , models, and hypotheses that are o v e r s i m p l i f i e d and r e s t r i c t e d i n t h e i r a p p l i c a b i l i t y . I t should be c l e a r that no model or hypothesis concerning g e n e r a l p r i n c i p l e s of hormone a c t i o n can be based upon the r e s u l t s obtained f o r a few s i m i l a r s p e c i e s . Yet, we f i n d that many of the p o i n t s made by Beach (1971) i n h i s t i m e l e s s paper on the hormonal f a c t o r s c o n t r o l l i n g d i f f e r e n t i a t i o n and c o p u l a t o r y behaviour i n the ramstergig and r e l a t e d s p e c i e s s t i l l h old true today. There i s s t i l l a tendency to act as i f a l l l a b o r a t o r y rodents are l i k e each other and are a l s o l i k e the ramstergig. In the ramstergig, " a l l r e l a t i o n s h i p s between i t s anatomical, p h y s i o l o g i c a l , and 7 b e h a v i o r a l c h a r a c t e r i s t i c s a r e c o m p l e t e l y known and n e v e r s u b j e c t t o c o n t r o v e r s y . " ( B e a c h , 1971, p . 2 4 9 ) . F u r t h e r m o r e , " t h e n e u r o n t o g e n y of t h e r a m s t e r g i g f o l l o w s p r e c i s e l y c u r r e n t t h e o r i e s d e s c r i b i n g t h e " o r g a n i z a t i o n a l " a c t i o n of g o n a d a l hormones." (Be a c h , 1971, p. 2 4 9 ) . F i n a l l y , male and f e m a l e s e x u a l b e h a v i o u r a r e " m u t u a l l y e x c l u s i v e i n r a m s t e r g i g s , and t h e r e f o r e t h e r a m s t e r g i g i s what i s t e c h n i c a l l y known as a " s t r a i g h t " s p e c i e s . M a l e s a l w a y s engage e x c l u s i v e l y i n m a s c u l i n e s e x u a l b e h a v i o u r and f e m a l e s d i s p l a y o n l y t h e f e m i n i n e m a t i n g p a t t e r n . " ( B e a c h , 1971, p . 2 5 1 ) . The t e n d e n c y t o l o o k f o r s i m i l a r i t i e s between r o d e n t s may have been a d v a n t a g e o u s i n t h e e a r l y s t a g e s o f hormone r e s e a r c h , and c o u l d be now i f r e s e a r c h e r s would a l s o l o o k f o r d i f f e r e n c e s and d e v e l o p models w h i c h c o u l d a c c o u n t f o r b o t h i n t e r s p e c i f i c d i f f e r e n c e s and s i m i l a r i t i e s . However, t h e r e i s l i t t l e room f o r t h e i n v e s t i g a t i o n o f between s p e c i e s d i f f e r e n c e s i n t h e h o r m o n a l r e g u l a t i o n o f d i f f e r e n t i a t i o n and b e h a v i o u r when t h e t o t a l number of commonly u s e d l a b o r a t o r y r o d e n t s d o e s n o t e x c e e d f i v e ( r a t , mouse, h a m s t e r , g u i n e a p i g , g e r b i l ) . Of t h e s e f i v e , t h e g u i n e a p i g i s no l o n g e r u s e d f r e q u e n t l y , t h e r a t and mouse a r e f a i r l y s i m i l a r i n known h o r m o n e - b e h a v i o u r r e l a t i o n s h i p s , t h e g e r b i l i s a newcomer, and t h e h a m s t e r d i f f e r s f r o m t h e r a t and mouse i n many r e s p e c t s . F u r t h e r m o r e , t h e r a t i s u s e d p r i m a r i l y f o r s t u d i e s on hormones and d i f f e r e n t i a t i o n , s e x u a l b e h a v i o u r , and f e e d i n g b e h a v i o u r , t h e mouse i s u s e d e x t e n s i v e l y and a l m o s t e x c l u s i v e l y f o r s t u d i e s on i n t e r - m a l e a g g r e s s i o n , t h e g u i n e a p i g was u s e d f o r s t u d i e s on d i f f e r e n t i a t i o n , and t h e g e r b i l i s u s e d p r i m a r i l y f o r s t u d i e s on s c e n t m a r k i n g and a g g r e s s i o n . T h u s , 8 even f o r t h e l a b o r a t o r y r o d e n t s a v a i l a b l e , e a c h i s u s e d p r i m a r i l y f o r t h e s t u d y o f t h e h o r m o n a l l y m e d i a t e d b e h a v i o u r i t d i s p l a y s b e s t . F o r example, b o t h h a m s t e r s and g e r b i l s s c e n t mark. However, t h e m a r k i n g r e s p o n s e and t h e e f f e c t s o f hormones on s c e n t g l a n d t i s s u e a r e most o b v i o u s i n t h e g e r b i l , w h i c h has become t h e a n i m a l of c h o i c e f o r t h i s t y p e o f r e s e a r c h . T h i s t y p e o f s e l e c t i v e e x a m i n a t i o n of b e h a v i o u r s w i t h i n a s p e c i e s r e s u l t s i n a r e l a t i v e p a u c i t y o f i n f o r m a t i o n i n some a r e a s where c o m p a r i s o n s would be u s e f u l . I t a l s o p r o v i d e s a p l e t h o r a of i n f o r m a t i o n , o f t e n r e d u n d a n t , i n a few s p e c i f i c a r e a s f o r a few s p e c i f i c s p e c i e s . F o r example, t h e r e a r e e x c e e d i n g l y few s t u d i e s t h a t have examined t h e e f f e c t s of p e r i n a t a l TP a d m i n i s t r a t i o n on s e x u a l b e h a v i o u r i n t h e mouse a l t h o u g h t h e r e a r e a l a r g e number w h i c h have examined t h e e f f e c t s of p e r i n a t a l TP on a g g r e s s i o n i n t h i s s p e c i e s . I t would seem t h a t two l i n e s o f a c t i o n need t o be t a k e n t o remedy t h i s s i t u a t i o n . F i r s t , a r e a s o f s p a r s e i n f o r m a t i o n i n e x i s t i n g l a b o r a t o r y r o d e n t s s h o u l d be i d e n t i f i e d and s t e p s t a k e n t o f i l l t h e s e gaps i n our knowledge. Second, e v e r y a t t e m p t s h o u l d be made t o i n c r e a s e t h e number of r o d e n t s p e c i e s p r e s e n t l y a v a i l a b l e i n t h e l a b o r a t o r y . F u r t h e r m o r e , r o d e n t s w h i c h l i v e i n v e r y d i f f e r e n t n a t u r a l h a b i t a t s would be t h e most d e s i r a b l e new a d d i t i o n . S t u d y i n g t h e d i f f e r e n c e s between r o d e n t s p e c i e s of d i f f e r e n t e n v i r o n m e n t s w i l l a l l o w r e s e a r c h e r s t o d e t e r m i n e w h i c h h o r m o n e - b e h a v i o u r r e l a t i o n s h i p s r e f l e c t u n d e r l y i n g p r i n c i p l e s of h o r m o n a l a c t i o n and w h i c h h o r m o n e - b e h a v i o u r r e l a t i o n s h i p s r e f l e c t s p e c i f i c a d a p t a t i o n s t o p a r t i c u l a r e n v i r o n m e n t s . G r a n t e d , i t i s not s i m p l e t o i n t r o d u c e a r o d e n t i n t o a l a b o r a t o r y s e t t i n g and b e g i n 9 a breeding colony. However, bringing new rodents into the laboratory i s essential to the study of general p r i n c i p l e s and mechanisms which underlie physiological and behavioural development in rodents and indeed, in mammals. Un t i l recently, the hamster appeared to be the only unusual laboratory rodent. However, the use of the Mongolian g e r b i l as a laboratory rodent has increased greatly in the last decade and there are clear indications that the g e r b i l d i f f e r s in many respects from other laboratory rodents. The hormonal mediation of food intake and body weight i s one example of thi s difference. To date, the g e r b i l i s the only rodent examined in which sex steroids may not be primarily responsible for sex differences in food intake and body weight. The g e r b i l also d i f f e r s from other rodents in the a b i l i t y to u t i l i z e saline and conserve water (Winkelmann & Getz, 1962; Wong, 1977), the type of t e r r i t o r i a l behaviours displayed (Rieder & Reynierse, 1971; o Yahr, 1981), s o c i a l and socio-sexual behaviour (Agren, 1976, 1980; Agren & Meyerson, 1973, 1975, 1977a,b, 1978; Roper & Polidioukis, 1977), and perhaps a variety of other behaviours as well. In addition, l i k e the hamster and unlike the rat, the major adrenal steroid of the g e r b i l i s C o r t i s o l rather than corticosterone (Oliver & Peron, 1964). Furthermore, the g e r b i l i s a desert animal, as i s the hamster, and one would expect t h i s harsh environment to produce a variety of physiological and behavioural adaptations not seen in the rat. Thus, the information concerning the hormonal regulation of d i f f e r e n t i a t i o n and behaviour in the g e r b i l would aid in developing and refinin g present models of the actions of sex 10 s t e r o i d s on d e v e l o p m e n t and b e h a v i o u r i n r o d e n t s . A l t h o u g h t h e g e r b i l has been u s e d e x t e n s i v e l y f o r s t u d i e s on t h e h o r m o n a l r e g u l a t i o n of s c e n t m a r k i n g , a g g r e s s i o n , and, i n t h e male, s e x u a l b e h a v i o u r , r e l a t i v e l y l i t t l e work has been done on o t h e r h o r m o n a l l y m e d i a t e d b e h a v i o u r s . T h i s i s e s p e c i a l l y t h e c a s e i n t h e f e m a l e g e r b i l , w h i c h has n o t r e c e i v e d a g r e a t d e a l of a t t e n t i o n . A p p a r e n t l y t h e r e a r e o n l y two s t u d i e s (Maass & Wade, 1977; Roy, Maass & Wade, 1977) t h a t have examined t h e e f f e c t s o f sex s t e r o i d s on f o o d i n t a k e and body w e i g h t i n t h e g e r b i l . F u r t h e r m o r e , t h e r e a p p e a r s t o be o n l y one s t u d y i n w h i c h n e o n a t a l TP t r e a t m e n t was a d m i n i s t e r e d f o r any r e a s o n and i n t h i s s t u d y , s c e n t m a r k i n g , r a t h e r t h a n s e x u a l b e h a v i o u r , was examined ( T u r n e r , 1975). F i n a l l y , a l t h o u g h r e p r o d u c t i v e b e h a v i o u r i n t h e i n t a c t f e m a l e g e r b i l has been s t u d i e d ( e . g . , B a r f i e l d & Beeman, 1968; N o r r i s & Adams, 1974, 1981a,b,c; V i c k & Banks, 1969) and t h e b e h a v i o u r a l r e p e r t o i r e d e s c r i b e d ( B u r l e y , 1979), few s t u d i e s have m a n i p u l a t e d sex s t e r o i d s t o d e t e r m i n e t h e i r i n f l u e n c e on s e x u a l b e h a v i o u r . Kuehn & Z u c k e r (1968) f o u n d t h a t t h e a d m i n i s t r a t i o n of 6 pq EB 45 h r b e f o r e t e s t i n g p l u s t h e a d m i n i s t r a t i o n o f 400 pq P 9 h r p r i o r t o t e s t i n g would e l i c i t h i g h l e v e l s o f r e c e p t i v i t y i n t h e f e m a l e g e r b i l . McDermott & C a r t e r (1980) and McDermott, F i s c h e r , & C a r t e r (1980) have done some p r e l i m i n a r y work w h i c h i n d i c a t e s t h a t a c u t e EB a d m i n i s t r a t i o n i s not s u f f i c i e n t t o e l i c i t r e c e p t i v i t y and t h a t P i n i t i a l l y f a c i l i t a t e s r e c e p t i v i t y i n t h e s e a n i m a l s w h i l e l a t e r e x e r t i n g an i n h i b i t o r y e f f e c t . To t h e b e s t of my knowledge, t h e r e a r e no o t h e r s t u d i e s t h a t have examined t h e e f f e c t s o f sex s t e r o i d s on t h e s e b e h a v i o u r s i n t h e g e r b i l . I t 11 would a p p e a r t h a t v e r y l i t t l e i s known of t h e i n f l u e n c e of sex hormones on s e x u a l d i f f e r e n t i a t i o n , s e x u a l b e h a v o u r , and f o o d i n t a k e and body w e i g h t r e g u l a t i o n i n t h e g e r b i l . The g e r b i l i s from an e n v i r o n m e n t q u i t e u n l i k e t h a t of t h e r a t . I t i s i n e v i t a b l e t h a t a v a r i e t y o f a d a p t a t i o n s t o t h i s e n v i r o n m e n t have o c c u r r e d , some of w h i c h w i l l be r e f l e c t e d i n h o r m o n a l l y m e d i a t e d b e h a v i o u r s . The p r e s e n t s e r i e s of s t u d i e s i n t h e f e m a l e g e r b i l w i l l : ( 1 ) d e t e r m i n e t h e d ose and t e m p o r a l p a r a m e t e r s of o v a r i a n s t e r o i d m e d i a t i o n of s e x u a l r e c e p t i v i t y , ( 2 ) examine t h e e f f e c t s of o v a r i a n s t e r o i d s on f o o d i n t a k e and body w e i g h t r e g u l a t i o n , ( 3 ) i n v e s t i g a t e t h e e f f e c t s of p e r i n a t a l a n d r o g e n s on s e x u a l d i f f e r e n t i a t i o n and t h e c a p a c i t y t o d i s p l a y s e x u a l b e h a v i o u r i n a d u l t h o o d , and ( 4 ) examine t h e p o s s i b i l i t y t h a t t h e e x t e n t o f n a t u r a l l y o c c u r r i n g s e x u a l d i f f e r e n t i a t i o n c a n p r e d i c t i n t e r s p e c i f i c d i f f e r e n c e s i n t h e h o r m o n a l r e g u l a t i o n o f f o o d i n t a k e and body w e i g h t . F u r t h e r s t u d y of h o r m o n a l e f f e c t s i n t h e g e r b i l s h o u l d b r i n g us one s t e p c l o s e r t o an u n d e r s t a n d i n g o f h o r m o n a l a c t i o n s as w e l l a s p r o v i d i n g i n f o r m a t i o n t h a t w i l l a s s i s t i n s e p a r a t i n g a d a p t i v e mechanisms from more u n i v e r s a l mechanisms o f hormone a c t i o n . 1 2 SECTION l a Dose and T e m p o r a l P a r a m e t e r s of O v a r i a n S t e r o i d E f f e c t s on S e x u a l R e c e p t i v i t y E s t r o g e n and p r o g e s t e r o n e a r e t h e p r i m a r y r e g u l a t o r s o f s e x u a l r e c e p t i v i t y i n t h e f e m a l e r o d e n t . O v a r i e c t o m y a b o l i s h e s r e c e p t i v i t y whereas e s t r o g e n and p r o g e s t e r o n e r e s t o r e r e c e p t i v i t y i n o v a r i e c t o m i z e d a n i m a l s i f t h e a p p r o p r i a t e hormone d o s e s a r e a d m i n i s t e r e d i n a s p e c i f i c t e m p o r a l s e q u e n c e . The minimum d o s e s o f e s t r o g e n and p r o g e s t e r o n e r e q u i r e d , t h e f r e q u e n c y o f e s t r o g e n a d m i n i s t r a t i o n , and t h e t e m p o r a l s e q u e n c e of t h e two s t e r o i d s f o r t h e e l i c i t a t i o n o f maximal r e c e p t i v i t y v a r i e s somewhat among r o d e n t s p e c i e s (Beach ,1976; F e d e r , 1978). F o r example, f e m a l e r a t s and h a m s t e r s w i l l e x h i b i t . h i g h l e v e l s of r e c e p t i v i t y when g i v e n 5-6 ^pg EB 24-48 h r b e f o r e t e s t i n g p l u s 500 pq P 3-4 h r p r i o r t o t e s t i n g ( C a r t e r , L a n d a u e r , T i e r n e y , & J o n e s , 1976; Hardy & de B o l d , 1971) w h i l e some s t r a i n s o f f e m a l e mice r e q u i r e more p r o l o n g e d e s t r o g e n t r e a t m e n t f o r t h e e l i c i t a t i o n o f maximal r e c e p t i v i t y ( G o r z a l k a & Whalen, 1974). Thus, t r e a t m e n t s t h a t e l i c i t h i g h l e v e l s of r e c e p t i v i t y i n one s p e c i e s do n o t n e c e s s a r i l y e l i c i t h i g h l e v e l s o f r e c e p t i v i t y i n a d i f f e r e n t s p e c i e s s i n c e d o s e a n d / o r t e m p o r a l p a t t e r n i n g r e q u i r e m e n t s may d i f f e r . Few r e s e a r c h e r s have i n v e s t i g a t e d t h e d ose and t e m p o r a l p a r a m e t e r s o f o v a r i a n s t e r o i d e f f e c t s on r e c e p t i v i t y i n t h e f e m a l e g e r b i l . McDermott & c o w o r k e r s (1981) have d e t e r m i n e d t h a t i n t h e g e r b i l , a s i n o t h e r r o d e n t s , c h r o n i c P a d m i n i s t r a t i o n e x e r t s an i n i t i a l f a c i l i t a t o r y e f f e c t on 1 3 r e c e p t i v i t y but l a t e r e x e r t s an i n h i b i t o r y e f f e c t . Kuehn & Z u c k e r (1968) f o u n d t h a t t h e a d m i n i s t r a t i o n of 6 jug EB 24-48 hr b e f o r e t e s t i n g p l u s t h e a d m i n i s t r a t i o n of 400 }iq P 9 h r p r i o r t o t e s t i n g w ould e l i c i t h i g h l e v e l s of r e c e p t i v i t y i n o v a r i e c t o m i z e d f e m a l e g e r b i l s . However, t h e i r c h o i c e of t h a t s p e c i f i c r e g i m e n a p p e a r s a r b i t r a r y . I t i s p o s s i b l e t h a t l e v e l s of r e c e p t i v i t y s i m i l a r t o t h o s e o b s e r v e d by Kuehn & Z u c k e r (1968) m i g h t be o b t a i n e d w i t h c o n s i d e r a b l y l o w e r d o s e s w h i c h would a p p r o x i m a t e endogenous s t e r o i d l e v e l s . In a d d i t i o n , when e x a m i n i n g t h e e f f e c t s o f e x p e r i m e n t a l v a r i a b l e s on s e x u a l r e c e p t i v i t y , i t i s f r e q u e n t l y d e s i r a b l e t o use d o s e s t h a t do n o t e l i c i t maximal r e c e p t i v i t y . I f an a n i m a l i s a l r e a d y r e s p o n d i n g m a x i m a l l y , any f a c i l i t a t o r y e f f e c t o f t h e i n d e p e n d e n t v a r i a b l e on r e c e p t i v i t y w i l l be masked. The use o f d o s e s w h i c h i n d u c e m o d e r a t e l e v e l s of r e c e p t i v i t y overcome t h i s p r o b l e m w h i l e s t i l l a l l o w i n g room f o r t h e o b s e r v a t i o n of i n h i b i t i n g e f f e c t s as w e l l . T h us, i t would a p p e a r t h a t b e f o r e any n o n - p a r a m e t r i c r e s e a r c h c a n be p e r f o r m e d on t h e s e x u a l b e h a v i o u r of t h e f e m a l e g e r b i l , d o se and t e m p o r a l t h r e s h o l d s must f i r s t be e s t a b l i s h e d . GENERAL METHODS A l l e x p e r i m e n t a l a n i m a l s were p u r c h a s e d f rom Tumblebrook Farms (West B r o o k f i e l d , MA) a t 90 d a y s of age, h o u s e d i n p a i r s , and k e p t on a r e v e r s e d , 12:12 h r l i g h t - d a r k c y c l e w i t h f o o d and w a t er a v a i l a b l e ad l i b i t u m . To e l i m i n a t e i n d i v i d u a l d i f f e r e n c e s i n c i r c u l a t i n g hormone l e v e l s c a u s e d by e x p e r i m e n t a l c o n d i t i o n s , a l l a n i m a l s were b i l a t e r a l l y o v a r i e c t o m i z e d . A l l E B - p r i m e d a n i m a l s r e c e i v e d 10 pq EB 48 and 24 hr b e f o r e t e s t i n g u n l e s s 1 4 o t h e r w i s e n o t e d . A l s o , when t e s t s of s e x u a l r e c e p t i v i t y o c c u r r e d more t h a n one week a f t e r s u r g e r y , a n i m a l s r e c e i v e d a p r i m i n g d ose o f 10 ug EB one week p r i o r t o t e s t i n g . EB and P were d i s s o l v e d i n p e a n u t o i l and a l l i n j e c t i o n s were g i v e n s u b c u t a n e o u s l y . P l e x i g l a s chambers c o n t a i n i n g a b o u t 3 cm S a n - i -c e l b e d d i n g m a t e r i a l and m e a s u r i n g 30 cm (1) x 30 cm (w) x 45.5 cm (h) were u s e d f o r s e x u a l t e s t i n g . A l l t e s t s o c c u r r e d between 2 and 6 h r a f t e r t h e o n s e t o f t h e d a r k p o r t i o n o f t h e l i g h t - d a r k c y c l e . T e s t s of s e x u a l r e c e p t i v i t y l a s t e d f o r 20 min o r f o r an i n t e r v a l of 10 mounts w i t h p e l v i c t h r u s t i n g by a s e x u a l l y v i g o r o u s male, w h i c h e v e r came f i r s t . The e l i c i t a t i o n of l o r d o s i s ( t h e e l e v a t i o n o f t h e h i n d q u a r t e r s and d o r s o f l e x i o n of t h e t a i l , e x p o s i n g t h e p e r i n e a l r e g i o n and f a c i l i t a t n g male i n t r o m i s s i o n ) was r e c o r d e d and t h e l o r d o s i s q u o t i e n t (LQ, l o r d o s i s / m o u n t x 100) was u s e d as t h e p r i m a r y i n d i c a t o r of s e x u a l r e c e p t i v i t y . The a u t h o r has o b s e r v e d t h a t u n r e c e p t i v e f e m a l e g e r b i l s a r e q u i t e a g g r e s s i v e t o w a r d s m a l e s a t t e m p t i n g t o mount. Thus, b e c a u s e t h e a b s e n c e o f mounts r e f l e c t s a l a c k o f r e c e p t i v i t y r a t h e r t h a n a l a c k o f male s e x u a l a c t i v i t y , an LQ o f 0 was a s s i g n e d t o t h e s u b j e c t . Most e x p e r i m e n t s r e q u i r e d t h a t t e s t i n g be c a r r i e d out o v e r s e v e r a l h o u r s w i t h o n l y a p o r t i o n o f t h e a n i m a l s b e i n g t e s t e d a t any g i v e n t i m e . Thus, whenever p o s s i b l e , c o u n t e r b a l a n c i n g was i n c o r p o r a t e d i n t o t h e e x p e r i m e n t a l d e s i g n w i t h a n i m a l s f r o m e a c h g r o u p b e i n g t e s t e d a t t h e v a r i o u s s u b s e t t i m e s . F o r t h e p u r p o s e s o f t h e p r e s e n t work, t h e t e r m "maximal r e c e p t i v i t y " w i l l be u s e d t o r e f e r t o LQs n e a r 100 w h i l e t h e t e r m " h i g h l e v e l s o f r e c e p t i v i t y " w i l l be u s e d t o r e f e r t o LQs 15 o f 70 or a b o v e . "Moderate r e c e p t i v i t y " w i l l be u s e d t o r e f e r t o LQs between and 41 and 69 and "low r e c e p t i v i t y " w i l l be u s e d t o r e f e r t o LQs of 40 and below. EXPERIMENT 1 B e c a u s e a n i m a l s c a n n o t a l l be t e s t e d a t t h e same t i m e , knowledge of t h e d u r a t i o n of t h e s y n e r g i s t i c e f f e c t s o f P w i t h EB on r e c e p t i v i t y i s e s s e n t i a l b e f o r e c a r r y i n g o u t o t h e r t e s t s of s e x u a l r e c e p t i v i t y . L i s k (1960) f o u n d t h a t maximal r e c e p t i v i t y i n E B - p r i m e d f e m a l e r a t s o c c u r r e d a b o u t 3 hr a f t e r P a d m i n i s t r a t i o n . D a t a on t h e d u r a t i o n of r e c e p t i v i t y i n r a t s a f t e r e s t r o g e n and p r o g e s t e r o n e t r e a t m e n t i s r e l a t i v e l y s p a r s e , w i t h most r e s e a r c h e r s ( e . g . , Quadagno, M c C u l l o u g h , & Langan, 1972; Whalen & G o r z a l k a , 1972; Whalen, 1974) t e s t i n g 3-6 hr a f t e r P a d m i n i s t r a t i o n . Kuehn & Z u c k e r ' s (1968) s t u d y s u g g e s t e d t h a t f e m a l e g e r b i l s would be r e c e p t i v e f o r more t h a n 9 h r a f t e r P t r e a t m e n t . T h u s , i n t h e p r e s e n t s t u d y , t h e d e c i s i o n was made t o b e g i n t e s t i n g 3 hr a f t e r P i n j e c t i o n and c o n t i n u e beyond t h e 9 h r p e r i o d examined by Kuehn & Z u c k e r ( 1 9 6 8 ) . Then, i f n e c e s s a r y , t h e t i m e d e l a y between P a d m i n i s t r a t i o n and s e x u a l t e s t i n g c o u l d be r e d u c e d o r e x t e n d e d . Method A f t e r a one week r e c o v e r y p e r i o d , 36 a n i m a l s were p r i m e d w i t h EB and r a n d o m l y a s s i g n e d t o one o f f o u r g r o u p s ( n = 9 / g r o u p ) , w i t h t e s t i n g o c c u r r i n g e i t h e r 3, 6, 9, o r 12 h r a f t e r t h e a d m i n i s t r a t i o n o f 500 ug P. S i n c e r e c e p t i v i t y a p p e a r e d e q u a l i n a l l o f t h e s e g r o u p s , a d d i t i o n a l g r o u p s were t e s t e d 0, 1, 2, 3 (n=9), 12, 15, 18 (n=8), and 18, 21, and 24 (n=!3) hr a f t e r P 16 a d m i n i s t r a t i o n . A n i m a l s s e r v e d i n o n l y one g r o u p w i t h e a c h g r o u p b e i n g r e p r e s e n t e d d u r i n g a g i v e n s u b t e s t p e r i o d . R e s u l t s and D i s c u s s i o n The r e s u l t s s u g g e s t e d t h a t maximal r e c e p t i v i t y o c c u r r e d 2 h r a f t e r t h e a d m i n i s t r a t i o n o f P and c o n t i n u e d f o r a b o u t 16 h r ( F i g u r e 1 ) . A f t e r d e t e r m i n i n g t h a t t h e p a i r s o f o v e r l a p p i n g d a t a p o i n t s a t 3, 12, and 18 hr were n o t s i g n i f i c a n t l y d i f f e r e n t , d a t a f o r e a c h o f t h e s e p o i n t s were combined, g i v i n g a t o t a l o f 11 g r o u p s ( i . e . , 0, 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 h r ) . A one-way a n a l y s i s o f v a r i a n c e p e r f o r m e d on t h e d a t a r e v e a l e d a s i g n i f i c a n t e f f e c t of t i m e between P a d m i n i s t r a t i o n and t e s t i n g , F ( 1 0 , 1 2 8 ) = 24.43, p_ < 0.0001. A s u b s e q u e n t Newman-Keul's a n a l y s i s i n d i c a t e d t h a t t h e mean LQs 0, 21, and 24 h r a f t e r P a d m i n i s t r a t i o n were s i g n i f i c a n t l y l o w e r t h a n t h e mean LQs f o r a l l o t h e r t e s t t i m e s , p_ < 0.05. F u r t h e r m o r e , a l t h o u g h t h e mean LQ a t 1 h r was s i g n i f i c a n t l y g r e a t e r t h a n t h e mean LQs a t 0, 21, and 24 h r , p_ < 0.05, i t was a l s o s i g n i f i c a n t l y l e s s t h a n t h e mean LQs a t 2, 3, 6, 9, and 12 h r , g < 0.05, and d i d not d i f f e r f r o m t h e mean LQs a t 15 and 18 h r . T h e s e r e s u l t s i n d i c a t e t h a t t h e o n s e t o f r e c e p t i v i t y b e g i n s a b o u t 1 h r a f t e r P a d m i n i s t r a t i o n , r e a c h e s a maximum 2 hr a f t e r P a d m i n i s t r a t i o n , and c o n t i n u e s f o r a b o u t 16 h r . Sometime between 18 and 21 h r a f t e r t h e a d m i n i s t r a t i o n o f P, r e c e p t i v i t y s h a r p l y d e c l i n e s and, by 24 h r a f t e r t h e a d m i n i s t r a t i o n o f P, r e c e p t i v i t y i s once a g a i n a t a minimum. Th u s , i f 10 jug EB i s a d m i n i s t e r e d 48 and 24 h r p r i o r t o t e s t i n g , t h e a d m i n i s t r a t i o n of 500 j j g P w i l l p r o v i d e a l a r g e t i m e window i n w h i c h a n i m a l s c a n be t e s t e d and maximal r e c e p t i v i t y i n s u r e d . 1 7 FIGURE 1. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s a t v a r i o u s t i m e s a f t e r p r o g e s t e r o n e a d m i n i s t r a t i o n . R e c e p t i v i t y i s e x p r e s s e d a s t h e r a t i o o f l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . A n i m a l s r e c e i v e d 10 pq e s t r a d i o l b e n z o a t e 48 and 24 h r b e f o r e t e s t i n g and 500 ^ug p r o g e s t e r o n e 0-24 h r p r i o r t o t e s t i n g . B r e a k s i n g r a p h r e p r e s e n t t e s t s w i t h d i f f e r e n t s e t s o f a n i m a l s . Hours 19 EXPERIMENT 2 I t has been f o u n d t h a t t h e dose of P a d m i n i s t e r e d i n f l u e n c e s t h e d e g r e e and d u r a t i o n of r e c e p t i v i t y i n t h e h a m s t e r ( C i a c c i o & L i s k , 1971) and t h e r a t (Fadem, B a r f i e l d , & Whalen, 1979). I t i s p o s s i b l e t h a t t h e 500 pq P u s e d i n E x p e r i m e n t 1 was much g r e a t e r t h a n r e q u i r e d t o e l i c i t maximal r e c e p t i v i t y i n E B - p r i m e d g e r b i l s . T h i s e x p e r i m e n t was d e s i g n e d t o i n v e s t i g a t e t h e p o s s i b i l i t y t h a t a l o w e r d o s e of P might e l i c i t maximal r e c e p t i v i t y and t o d e t e r m i n e an a p p r o p r i a t e dose o f P f o r s i t u a t i o n s i n w h i c h o n l y m oderate l e v e l s of r e c e p t i v i t y would be d e s i r e d ( i . e . , when a f a c i l i t a t i o n e f f e c t m i g h t o c c u r ) . Method A f t e r a one week r e c o v e r y p e r i o d , 60 E B - p r i m e d a n i m a l s were rand o m l y a s s i g n e d t o one of s i x g r o u p s (n=10/group) r e c e i v i n g e i t h e r 0, 10, 50, 100, 250, o r 500 jug P 3 h r p r i o r t o t e s t i n g . T h i s t i m e d e l a y was c h o s e n b e c a u s e E x p e r i m e n t 1 i n d i c a t e d t h a t a l l a n i m a l s r e c e i v i n g 500 pq P would be m a x i m a l l y r e c e p t i v e a t t h i s t i m e . R e s u l t s and D i s c u s s i o n The r e s u l t s s u g g e s t e d t h a t 10 pq P e l i c i t e d m i n i m a l s e x u a l r e s p o n d i n g (LQ < 2 0 ) , t h a t 50 j j g P e l i c i t e d m oderate r e s p o n d i n g (LQ < 6 0 ) , and t h a t 100^ug o r more o f P e l i c i t e d h i g h l e v e l s o f s e x u a l r e c e p t i v i t y (LQ < 1 0 0 ) ( F i g u r e 2 ) . A one-way a n a l y s i s o f v a r i p e r f o r m e d on t h e d a t a c o n f i r m e d a s i g n i f i c a n t e f f e c t o f d o s e , F ( 5 , 5 4 ) = 22. 12, p_ < 0.0001. A Newman-Keul' s c o m p a r i s o n r e v e a l e d t h a t r e c e p t i v i t y i n a n i m a l s g i v e n 10^ug P d i d not d i f f e r f r o m t h a t o b s e r v e d i n c o n t r o l s , £ < 0.05. In a d d i t i o n , a l t h o u g h 50 ^jg P d i d s i g n i f i c a n t l y i n c r e a s e r e c e p t i v i t y when 20 FIGURE 2. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s d o s e s o f p r o g e s t e r o n e . R e c e p t i v i t y i s e x p r e s s e d as t h e r a t i o o f l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . A n i m a l s r e c e i v e d 10 ^ug e s t r a d i o l b e n z o a t e 48 and 24 h r b e f o r e t e s t i n g and 0-500 ^ug p r o g e s t e r o n e 3-4 h r p r i o r t o t e s t i n g . 21 o o o 00 o CD O o CM 001.x ;uno|Ai/sisopjo-| 22 compared t o o i l c o n t r o l s , p_ < 0.05, d o s e s o f 100 pq P and g r e a t e r e l i c i t e d s i g n i f i c a n t l y h i g h e r s c o r e s t h a n d i d t h e 50 ^ g d o s e , p_ < 0.05. Thus, i t would a p p e a r t h a t a dose o f 50 jug P s h o u l d be u s e d when t h e e l i c i t a t i o n of m o d e r a t e l e v e l s o f r e c e p t i v i t y i s d e s i r e d w h i l e 100 jjg P or more s h o u l d be u s e d t o e l i c i t h i g h l e v e l s o f r e c e p t i v i t y i n E B - p r i m e d a n i m a l s . In a d d i t i o n , t h e p r e s e n t r e s u l t s s u g g e s t t h a t t h e p r o l o n g e d e f f e c t of P o b s e r v e d i n E x p e r i m e n t 1 was p r o b a b l y due, t o some e x t e n t , t o t h e use of a g r e a t e r t h a n n e c e s s a r y dose o f P. EXPERIMENT 3 I t has been f o u n d i n t h e r a t (Quadagno e t a l . , 1972) and hams t e r ( C a r t e r & P o r g e s , 1974) t h a t t h e d e g r e e and d u r a t i o n o f r e c e p t i v i t y i s a l s o i n f l u e n c e d by EB d o s e . T h u s , t h e e f f e c t s o b s e r v e d i n E x p e r i m e n t 1 may have a l s o been due, i n p a r t , t o t h e dose o f EB a d m i n i s t e r e d . To i n v e s t i g a t e t h i s p o s s i b i l i t y , and t o d e t e r m i n e t h e minimum d o s e o f EB r e q u i r e d t o e l i c i t maximal r e c e p t i v i t y , t h e P dose was h e l d c o n s t a n t w h i l e t h e dose of EB was v a r i e d . Method T w e n t y - e i g h t a n i m a l s were ra n d o m l y a s s i g n e d t o one o f f o u r g r o u p s ( n = 7 / g r o u p ) . A l l a n i m a l s r e c e i v e d a p r i m i n g dose o f 10 jug EB one week p r i o r t o t e s t i n g and t h e n r e c e i v e d e i t h e r 0.5, 1.0, 5.0, o r 10.0^ug EB 48 and 24 h r b e f o r e t e s t i n g . A dose o f 100 ^ug P was a d m i n i s t e r e d 3 hr p r i o r t o t e s t i n g a s E x p e r i m e n t 2 i n d i c a t e d t h a t t h i s dose o f P was t h e l o w e s t t h a t would e l i c i t m aximal r e c e p t i v i t y i n a n i m a l s r e c e i v i n g 10 ug EB. 23 R e s u l t s and D i s c u s s i o n R e s u l t s of t h e p r e s e n t e x p e r i m e n t s u g g e s t e d t h a t o n l y t h e 10 jug d o s e of EB was s u f f i c i e n t t o e l i c i t h i g h l e v e l s of r e c e p t i v i t y (LQ>80) when a d o s e o f 1 00 j j g P was a d m i n i s t e r e d ( F i g u r e 3 ) . A one-way a n a l y s i s o f v a r i a n c e p e r f o r m e d on t h e d a t a i n d i c a t e d a s i g n i f i c a n t e f f e c t o f EB d o s e , F ( 3 , 2 4 ) = 12.94, p_ < 0.0001. A Newman-Keul's t e s t r e v e a l e d t h a t t h e 10 jag EB d o se was s i g n i f i c a n t l y more e f f e c t i v e i n e l i c i t i n g h i g h l e v e l s o f r e c e p t i v i t y t h a n were t h e o t h e r EB d o s e s , p_ < 0.05. In a d d i t i o n , t h e 0.5 ^ j g EB d o s e was as e f f e c t i v e as t h e 1 .0 j j g d o s e , p > 0.05, but l e s s e f f e c t i v e t h a n o t h e r d o s e s , p_ < 0.05. EXPERIMENT 4 E x p e r i m e n t 3 i n d i c a t e d t h a t 10 pq EB, b u t n o t l o w e r d o s e s of EB, l e a d t o h i g h l e v e l s o f r e c e p t i v i t y when g i v e n i n c o n j u n c t i o n w i t h 100 pq P. However, i n t h e r a t , c h r o n i c a d m i n i s t r a t i o n o f EB c a n a l s o r e s u l t i n h i g h l e v e l s o f r e c e p t i v i t y ( D a v i d s o n , R o g e r s , S m i t h , & B l o c h , 1968; G o r z a l k a & R a i b l e , 1981; G r a y & G o r z a l k a , 1980). T h i s e x p e r i m e n t was d e s i g n e d : (1) t o d e t e r m i n e t h e d o s e - d e p e n d e n t e f f e c t s o f c h r o n i c a l l y a d m i n i s t e r e d EB on s e x u a l r e c e p t i v i t y i n t h e g e r b i l . and (2) t o d e t e r m i n e i f e s t r o g e n , i n t h e a b s e n c e of p r o g e s t e r o n e , i s c a p a b l e o f e l i c i t i n g s e x u a l r e c e p t i v i t y . Method T w e n t y - s e v e n a n i m a l s were r a n d o m l y a s s i g n e d t o one o f t h r e e g r o u p s (n=9/group) and r e c e i v e d d a i l y i n j e c t i o n s of 1, 10, o r 100 ^ug EB. B e c a u se p r e v i o u s r e s e a r c h i n r a t s i n d i c a t e d t h a t EB-24 FIGURE 3. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s d o s e s of e s t r o g e n . R e c e p t i v i t y i s e x p r e s s e d as t h e r a t i o o f l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . A n i m a l s r e c e i v e d 0.5 - 10.0 j j g e s t r a d i o l b e n z o a t e (EB) 48 and 24 h r b e f o r e t e s t i n g and 100 jjg p r o g e s t e r o n e 3-4 h r p r i o r t o t e s t i n g . 25 001- x iuno|Al/s|sopjo"| 26 i n d u c e d r e c e p t i v i t y d o e s not o c c u r u n t i l Day 3 of EB a d m i n i s t r a t i o n (Bermant & D a v i d s o n , 1974, p. 136), t h i s i n t e r v a l between f i r s t i n j e c t i o n and f i r s t t e s t was e mployed i n t h e p r e s e n t e x p e r i m e n t . T e s t i n g c o n t i n u e d u n t i l a n i m a l s i n e a c h g r o u p r e a c h e d a s y m p t o t i c l e v e l s o f s e x u a l r e s p o n d i n g (Day 12 o f E B ) . I t s h o u l d be n o t e d t h a t , d u r i n g s e x u a l t e s t i n g , s u b j e c t s were s i m u l t a n e o u s l y i n v o l v e d i n a f o o d i n t a k e and body w e i g h t s t u d y ( E x p e r i m e n t 9) and were w e i g h e d d a i l y t h r o u g h o u t s e x u a l t e s t i n g . R e s u l t s and D i s c u s s i o n The r e s u l t s o f t h e p r e s e n t e x p e r i m e n t s u g g e s t e d t h a t , a l t h o u g h 1 and 10 jjg o f EB were c a p a b l e of e l i c i t i n g some d e g r e e of s e x u a l r e c e p t i v i t y when a d m i n i s t e r e d c h r o n i c a l l y , o n l y t h e 100 p.q dose of EB a p p e a r e d a b l e t o e l i c i t f u l l s e x u a l r e c e p t i v i t y ( F i g u r e 4 ) . In a d d i t i o n , t h e e f f e c t s o f c h r o n i c EB on s e x u a l r e c e p t i v i t y were no t o b s e r v e d u n t i l Day 6 o f EB a d m i n i s t r a t i o n . A 3 x 10 r e p e a t e d m e asures a n a l y s i s o f v a r i a n c e p e r f o r m e d on t h e d a t a r e v e a l e d a s i g n i f i c a n t e f f e c t o f e s t r o g e n d o s e , F ( 2 , 2 4 ) = 10.11, g = 0.0007, a s i g n i f i c a n t e f f e c t of t e s t day, F ( 9 , 2 1 6 ) = 46.83, p_ < 0.0001, and a s i g n i f i c a n t d o s e by t e s t i n t e r a c t i o n , F ( 1 8 , 216) = 4.70, p_ < 0.0001. To d e t e r m i n e more p r e c i s e l y t h e n a t u r e o f t h e e f f e c t s , a Newman-Keul's t e s t was p e r f o r m e d on e a c h o f t h e s i g n i f i c a n t e f f e c t s (e*= 0 . 0 5 ) . I t was f o u n d t h a t t h e l e v e l s o f r e c e p t i v i t y e x h i b i t e d by a n i m a l s r e c e i v i n g 1 and 10 ^ug EB d i d n o t d i f f e r s i g n i f i c a n t l y f r o m e a c h o t h e r , a l t h o u g h t h e y were s i g n i f i c a n t l y l o w e r t h a n t h e l e v e l s o f r e c e p t i v i t y e x h i b i t e d by a n i m a l s r e c e i v i n g 100 jug EB. In a d d i t i o n , t e s t s o c c u r r i n g on Days 3-6 of EB a d m i n i s t r a t i o n 27 FIGURE 4. S e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s t e s t e d d a i l y and c h r o n i c a l l y a d m i n i s t e r e d v a r i o u s d o s e s o f e s t r o g e n . R e c e p t i v i t y i s e x p r e s s e d as t h e r a t i o o f l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . A n i m a l s r e c e i v e d d a i l y i n j e c t i o n s o f 1, 10, o r 100 e s t r a d i o l b e n z o a t e (EB) b e g i n n i n g on Day 1. T e s t i n g o c c u r r e d on Days 3-12. 29 p r o d u c e d s i g n i f i c a n t l y l o w e r r e c e p t i v i t y s c o r e s o v e r a l l t h a n t e s t s c o n d u c t e d on Days 7-12. F i n a l l y , i t was f o u n d t h a t t h e 1 and 10 jjq EB g r o u p s d i d n o t d i f f e r f r o m e a c h o t h e r on any o f t h e t e s t d a y s w h i l e s c o r e s o f t h e 100 pq EB g r o u p were f o u n d t o be s i g n i f i c a n t l y g r e a t e r t h a n t h e o t h e r g r o u p s from Day 7 o f EB onward. I t would a p p e a r t h a t o n l y t h e 100 ^ g EB dose i s s u f f i c i e n t t o e l i c i t maximal r e c e p t i v i t y when a d m i n i s t e r e d c h r o n i c a l l y w h i l e e i t h e r t h e 1 o r 10 pq EB dose w i l l e l i c i t l o w e r l e v e l s o f r e s p o n d i n g . I t i s of i n t e r e s t t h a t , a l t h o u g h 100 pq EB l e a d s t o h i g h l e v e l s o f r e s p o n d i n g , i t s i n f l u e n c e becomes a p p a r e n t a t a b o u t t h e same t i m e a s t h e l o w e r d o s e s . T h i s s u g g e s t s t h a t t h e r e i s a m i n i m a l r e q u i r e d p e r i o d o f c h r o n i c e x p o s u r e t o EB and t h a t t h i s p e r i o d i s i n d e p e n d e n t o f EB d o s e . GENERAL DISCUSSION The r e s u l t s o f E x p e r i m e n t 1 i n d i c a t e t h a t maximal r e c e p t i v i t y i n E B - p r i m e d g e r b i l s o c c u r s a p p r o x i m a t e l y 2 h r a f t e r t h e a d m i n i s t r a t i o n of 500^ug P and l a s t s f o r a b o u t 7 h r , w i t h h i g h . l e v e l s o f r e c e p t i v i t y b e i n g o b s e r v a b l e u n t i l 18 h r a f t e r P a d m i n i s t r a t i o n ( F i g u r e 1 ) . The d u r a t i o n of h i g h l e v e l s o f s e x u a l r e c e p t i v i t y was somewhat l o n g e r t h a n e x p e c t e d and i t i s p o s s i b l e t h a t t h e dose o f P a d m i n i s t e r e d was, t o some e x t e n t , r e s p o n s i b l e f o r t h i s e f f e c t . E x p e r i m e n t 2 i n d i c a t e d t h a t 100 ^ g P e l i c i t e d maximal r e c e p t i v i t y i n E B - p r i m e d a n i m a l s (LQ=100), s u g g e s t i n g t h a t t h e 500 pq P dose u s e d p r e v i o u s l y was i n e x c e s s o f t h e r e q u i r e d amount ( F i g u r e 2 ) . However, t h e r e s u l t s o f E x p e r i m e n t 3 f o r a n i m a l s g i v e n 10 ^ug EB p l u s 100 ^ug P (X LQ=83) 30 i n d i c a t e t h a t , t o i n s u r e maximal r e c e p t i v i t y , a d ose of 250 jiq P o r more s h o u l d be a d m i n i s t e r e d . The r e s u l t s o f E x p e r i m e n t 2 a l s o i m p l y t h a t a dose of 50 ^ g P e l i c i t s m o d e r a t e l e v e l s o f r e c e p t i v i t y i n E B - p r i m e d a n i m a l s . T h i s i s somewhat m i s l e a d i n g , however, as t h e e f f e c t o f P on r e c e p t i v i t y a p p e a r s t o be an a l l - o r - n o n e phenomenon. F o r example, w h i l e s i x a n i m a l s g i v e n 50 jiq P e x h i b i t e d maximal r e c e p t i v i t y , t h e o t h e r f o u r e x h i b i t e d no r e c e p t i v i t y . No a n i m a l s r e c e i v i n g t h e 50 ^ug P d o s e a c t u a l l y e x h i b i t e d an LQ w i t h i n t h e m o d e r a t e l y r e c e p t i v e r a n g e . R a t h e r , h a l f of t h e s u b j e c t s e x h i b i t e d h i g h l e v e l s o f r e c e p t i v i t y w h i l e t h e o t h e r h a l f e x h i b i t e d low l e v e l s o f r e c e p t i v i t y , r e s u l t i n g i n a mean LQ i n t h e m o d e r a t e r a n g e . T h i s b i m o d a l d i s t r i b u t i o n s u g g e s t s t h a t t h e t h r e s h o l d d ose o f P r e q u i r e d t o e l i c i t r e c e p t i v i t y i n EB-p r i m e d g e r b i l s i s between 50 and 100 p.q f o r a b o u t one h a l f of t h e a n i m a l s t e s t e d . The r e m a i n i n g a n i m a l s r e q u i r e a t h r e s h o l d d o se o f P somewhere between 0 and 50 ;ag. A b i m o d a l d i s t r i b u t i o n was a l s o o b s e r v e d i n E x p e r i m e n t 1, where t h e mean LQs a t 1 hr and a t 18-21 h r r e f l e c t t h e number of r e c e p t i v e and non-r e c e p t i v e a n i m a l s r a t h e r t h a n t h e a c t u a l modal LQs of t h e a n i m a l s w i t h i n t h e g r o u p . T h i s t y p e o f b i m o d a l d i s t r i b u t i o n i s a l s o s u g g e s t e d by t h e s i z e o f t h e s t a n d a r d e r r o r s . A b i m o d a l d i s t r i b u t i o n was n o t o b s e r v e d i n E x p e r i m e n t 3, where P d o s e was h e l d c o n s t a n t and EB d ose v a r i e d . In t h i s s i t u a t i o n , a more even d i s t r i b u t i o n o f LQs was o b s e r v e d , as s u g g e s t e d by t h e s m a l l e r s t a n d a r d e r r o r s ( F i g u r e 3) when compared t o t h e f i r s t e x p e r i m e n t . F o r example, LQs f o r t h e 5 ^jg d o se r a n g e d f r o m 30 t o 80, w i t h t h e mode a t 50. T h u s , i f 31 m o d e rate l e v e l s of r e c e p t i v i t y a r e d e s i r e d , i t w ould be most a p p r o p r i a t e t o use a d o se of 5 pq EB p l u s 100 pq P r a t h e r t h a n 10 pq EB p l u s 50 pq P. E x p e r i m e n t s 1-3 s u g g e s t t h a t t h e s y n e r g i s t i c a c t i o n of P w i t h EB on r e c e p t i v i t y i s a l l - o r - n o n e w h i l e t h e e f f e c t o f EB i s g r a d e d . T h i s t y p e of i n f o r m a t i o n c o u l d enhance t h e u n d e r s t a n d i n g of m o l e c u l a r mechanisms of e s t r o g e n and p r o g e s t e r o n e a c t i o n . The r e s u l t s o f E x p e r i m e n t 4 i n d i c a t e t h a t o n l y t h e 100 ug EB d o s e , when a d m i n i s t e r e d c h r o n i c a l l y , was c a p a b l e o f e l i c i t i n g maximal r e c e p t i v i t y w h i l e l o w e r d o s e s i n d u c e d low t o m o d erate l e v e l s o f r e c e p t i v i t y ( F i g u r e 4 ) . T h i s i s i n c o n t r a s t t o r a t s , where d o s e s of EB as s m a l l as 0.8 pq p e r day c a n e l i c i t m oderate t o h i g h l e v e l s of r e c e p t i v i t y (Bermant & D a v i d s o n , 1974; G o r z a l k a & R a i b l e , 1981). T h i s a l s o s u g g e s t s t h a t t h e g e r b i l i s more d e p e n d e n t t h a n t h e r a t on t h e s y n e r g i s t i c a c t i o n o f P w i t h EB f o r t h e i n d u c t i o n o f maximal r e c e p t i v i t y . A l t h o u g h 100 pq EB d i d p r o d u c e h i g h l e v e l s of r e c e p t i v i t y , i t was l a t e r f o u n d t h a t more p r o l o n g e d c h r o n i c a d m i n i s t r a t i o n of 100 j j g EB l e d t o b l a d d e r s t o n e s , h e m o r r h a g i n g , and d e a t h , w i t h i n i t i a l symptoms o c c u r r i n g as e a r l y as Day 30 of EB t r e a t m e n t . T h i s i n d i c a t e s t h a t 100 pq EB i s a s u p r a p h y s i o l o g i c a l d o s e , s u g g e s t i n g t h a t EB-i n d u c e d r e c e p t i v i t y i n f e m a l e g e r b i l s g i v e n t h i s d o se may be due t o a p h a r m a c o l o g i c a l e f f e c t . In any c a s e , i t c e r t a i n l y i s n o t a d v i s a b l e t o use t h i s d o se c h r o n i c a l l y f o r a p r o l o n g e d p e r i o d o f t i m e and r e s u l t s o b t a i n e d by t h i s method s h o u l d not be v i e w e d as r e p r e s e n t a t i v e o f n o r m a l p r o c e s s e s w i t h i n t h e g e r b i l . The f a i l u r e t o o b s e r v e r e c e p t i v i t y i n any of t h e EB t r e a t e d 32 a n i m a l s u n t i l Day 6 o f EB t r e a t m e n t i n d i c a t e s t h a t t h e g e r b i l r e q u i r e s more p r o l o n g e d EB t r e a t m e n t t h a n t h e r a t (Bermant & D a v i d s o n , 1974) f o r t h e i n d u c t i o n of r e c e p t i v i t y i n t h e a b s e n c e of P. F u r t h e r m o r e , t h e f i n d i n g t h a t r a i s i n g t h e d o s e o f EB d i d no t r e d u c e t h e m i n i m a l i n t e r v a l f o r i n i t i a l r e c e p t i v i t y s u g g e s t s t h a t t h e r e may be a minimum t i m e r e q u i r e m e n t b e f o r e t h e e f f e c t s o f c h r o n i c EB can be o b s e r v e d . T h i s f i n d i n g , p l u s t h e f i n d i n g t h a t l o w e r d o s e s o f EB g i v e n c h r o n i c a l l y w i l l i n d u c e moderate l e v e l s of r e c e p t i v i t y s u g g e s t s t h a t a c h r o n i c EB p a r a d i g m may p r o v e v a l u a b l e i n t h e e x a m i n a t i o n o f e x p e r i m e n t a l e f f e c t s when d a i l y t e s t i n g i s d e s i r a b l e . The r e s u l t s o f t h e p r e s e n t e x p e r i m e n t s i n d i c a t e t h a t t h e i n f l u e n c e of o v a r i a n s t e r o i d s on s e x u a l r e c e p t i v i t y i n t h e g e r b i l i s v e r y s i m i l a r t o t h a t o b s e r v e d i n o t h e r r o d e n t s . However, t h e r e s u l t s of E x p e r i m e n t s 1-4 do s u g g e s t t h a t , l i k e t h e h a m s t e r ( F e d e r , S i e g e l , & Wade, 1974), t h e g e r b i l i s more de p e n d e n t t h a n t h e r a t ( D a v i d s o n e t a l . , 1968) on t h e s y n e r g i s t i c a c t i o n o f P w i t h EB f o r t h e e l i c i t a t i o n of maximal r e c e p t i v i t y . 33 SECTION Ib E f f e c t s o f H o u s i n g C o n d i t i o n , A d r e n a l S t e r o i d s , and Hormone Dose on S e x u a l R e c e p t i v i t y G o r z a l k a & R a i b l e (1981) have f o u n d t h a t h o u s i n g c o n d i t i o n s ( i . e . , s o c i a l i s o l a t i o n v e r s u s g r o u p i n g ) i n f l u e n c e l o r d o s i s i n f e m a l e r a t s , t h e f i r s t d e m o n s t r a t i o n o f a d i f f e r e n t i a l h o u s i n g e f f e c t on s e x u a l r e c e p t i v i t y . T h i s r a i s e s t h e p o s s i b i l i t y t h a t f e m a l e g e r b i l s as w e l l a r e i n f l u e n c e d by h o u s i n g c o n d i t i o n s . Due t o t h e s p a c e l i m i t a t i o n s i n our c o l o n y , i t i s f r e q u e n t l y p r e f e r a b l e t o house g e r b i l s i n p a i r s . However, o c c a s i o n a l l y one a n i m a l w i l l d i e and t h e a g g r e s s i v e n a t u r e of t h e g e r b i l makes i t d i f f i c u l t t o f o r m a new p a i r by i n t r o d u c i n g a n o v e l cagemate ( A n i s k o , C h r i s t e n s o n , & B u e h l e r , 1973; M a r s t o n & Chang, 1.965; R i e d e r & R e y n i e r s e , 1971). S i n c e t h e s u r v i v o r would become s o c i a l l y i s o l a t e d , i t i s i m p o r t a n t t o d e t e r m i n e i f d i f f e r e n t i a l h o u s i n g c o n d i t i o n s a l t e r t h e s e x u a l r e s p o n d i n g o f t h e f e m a l e g e r b i l . G o r z a l k a & R a i b l e (1981) a l s o f o u n d t h a t t h e i s o l a t i o n i n d u c e d f a c i l i t a t i o n o b s e r v e d i n t h e f e m a l e r a t was a p p a r e n t l y m e d i a t e d by t h e a d r e n a l g l a n d , s i n c e a d r e n a l e c t o m y e l i m i n a t e d t h e e f f e c t . P r e s u m a b l y , s o c i a l i s o l a t i o n a c t s as a s t r e s s o r w h i c h , v i a t h e p i t u i t a r y - a d r e n a l a x i s , r e s u l t s i n a l t e r a t i o n s o f a d r e n a l s e c r e t i o n s ( H a t c h , W i b e r g , B a l a z s & G r i c e , 1963), one o r more of w h i c h t h e n a c t s upon t h e s y s t e m r e g u l a t i n g s e x u a l r e c e p t i v i t y . F o r example, s t r e s s c a n i n c r e a s e t h e s e c r e t i o n o f a d r e n o c o r t i c o t r o p i c hormone (ACTH) by t h e p i t u i t a r y w h i c h r e s u l t s i n i n c r e a s e d s e c r e t i o n of a d r e n a l P, 34 d e o x y c o r t i c o s t e r o n e , and c o r t i c o s t e r o n e . A l l o f t h e s e s t e r o i d s a r e known t o a l t e r r e c e p t i v i t y i n t h e f e m a l e r a t ( d e C a t a n z a r o , K n i p p i n g , & G o r z a l k a , 1981; G o r z a l k a & Whalen, 1977). C u l l e n & S c a r b o r o u g h (1970) f o u n d t h a t t h e g e r b i l was h i g h l y d e p e n d e n t on a d r e n a l s e c r e t i o n s f o r s u r v i v a l ( t h e r a t i s n o t ) , s u g g e s t i n g t h a t t h e a d r e n a l may p l a y an i m p o r t a n t r o l e i n m e d i a t i n g t h e e f f e c t s of e n v i r o n m e n t a l s t r e s s i n t h i s s p e c i e s a s w e l l . I t i s a l s o p o s s i b l e t h a t f a c t o r s o t h e r t h a n s o c i a l i s o l a t i o n ( i . e . , r e p e a t e d i n j e c t i o n s , h a n d l i n g , e x p o s u r e t o u n f a m i l i a r a n i m a l s ) may be s t r e s s f u l , r e s u l t i n g i n i n c r e a s e d a d r e n a l s t e r o i d s e c r e t i o n . T e s t i n g f o r t h e s e f a c t o r s w o u l d p r o v e t i m e c o n s u m i n g and d i f f i c u l t . However, t e s t i n g t h e e f f e c t s of a d r e n a l s t e r o i d s on r e c e p t i v i t y i s r e l a t i v e l y s i m p l e . The a d m i n i s t r a t i o n of a d r e n a l s t e r o i d s t o o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d a n i m a l s would r e v e a l any f a c i l i t a t o r y o r i n h i b i t o r y e f f e c t s o f a d r e n a l s t e r o i d s . Once t h e e f f e c t s of a d r e n a l s t e r o i d s on r e c e p t i v i t y a r e d e t e r m i n e d , p o s s i b l e e x p e r i m e n t a l c o n f o u n d s c a n be a v o i d e d by a l t e r a t i o n s i n e x p e r i m e n t a l d e s i g n . F i n a l l y , a l t h o u g h o v a r i a n s t e r o i d s may be t h e p r i m a r y r e g u l a t o r s of s e x u a l r e c e p t i v i t y i n o t h e r r o d e n t s ( B e a c h , 1976; K e l l e y & P f a f f , 1978), t h e p o s s i b i l i t y t h a t a d r e n a l s t e r o i d s a r e i n v o l v e d i n t h e m o d u l a t i o n of s e x u a l r e c e p t i v i t y i n t h e g e r b i l c a n n o t be e x c l u d e d . In f a c t , t h e r e i s e v i d e n c e t h a t , u n d e r c e r t a i n c o n d i t i o n s , a d r e n a l s t e r o i d s do i n f l u e n c e t h e l e v e l o f s e x u a l r e c e p t i v i t y i n f e m a l e r a t s ( d e C a t a n z a r o e t a l . , 1981; G r a y & G o r z a l k a , 1980; G o r z a l k a & Whalen, 1977). The f o l l o w i n g e x p e r i m e n t s were d e s i g n e d t o d e t e r m i n e (1) 35 t h e e f f e c t s o f d i f f e r e n t i a l h o u s i n g on r e c e p t i v i t y , (2) a p o t e n t i a l a d r e n a l m e d i a t i o n of any o b s e r v e d e f f e c t s , (3) any e f f e c t s of a d r e n a l e c t o m y i t s e l f on s e x u a l r e c e p t i v i t y , and (4) t h e e f f e c t s o f v a r i o u s a d r e n a l s t e r o i d s on s e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s . GENERAL METHODS The methods o u t l i n e d i n S e c t i o n l a were f o l l o w e d w i t h t h e a d d i t i o n o f t h e f o l l o w i n g p r o c e d u r e s . O v a r i e c t o m i z e d a n i m a l s n o t r e c e i v i n g a d r e n a l e c t o m i e s . were sham a d r e n a l e c t o m i z e d t o c o n t r o l f o r p o s s i b l e s t r e s s due t o t h e s u r g i c a l p r o c e d u r e i t s e l f , a l l a n i m a l s were g i v e n a two and one h a l f week r e c o v e r y p e r i o d b e f o r e t e s t i n g began. In a d d i t i o n , a l l a d r e n a l e c t o m i z e d a n i m a l s were g i v e n a c c e s s t o a 0.9% s a l i n e s o l u t i o n . Upon t e r m i n a t i o n o f an e x p e r i m e n t , a l l a d r e n a l e c t o m i z e d s u b j e c t s were a u t o p s i e d t o v e r i f y t h e s u c c e s s o f t h e s u r g i c a l p r o c e d u r e . EXPERIMENT 5 Comparing i s o l a t e d and g r o u p e d a n i m a l s , G o r z a l k a & R a i b l e (1981) f o u n d t h a t i s o l a t i o n f a c i l i t a t e d s e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d , E B - p r i m e d r a t s . The e f f e c t a p p e a r s t o be m e d i a t e d by t h e a d r e n a l g l a n d and, b e c a u s e t h e g e r b i l i s d e p e n d e n t upon a d r e n a l s e c r e t i o n s f o r s u r v i v a l ( C u l l e n & S c a r b o r o u g h , 1970), i t i s p o s s i b l e t h a t t h e g e r b i l may a l s o be i n f l u e n c e d by h o u s i n g c o n d i t i o n s . A t l e a s t one s t u d y has f o u n d t h a t s o c i a l i s o l a t i o n i n t h e g e r b i l i s s t r e s s f u l , a s i n d i c a t e d by an i n c r e a s e i n a s c o r b i c a c i d c o n t e n t of t h e a d r e n a l s (Hughes & N i c h o l a s , 1971). However, a s c o r b i c a c i d c o n t e n t p r o v i d e s o n l y 36 an i n d i r e c t measure of a d r e n a l s e c r e t i o n and t h e r e f o r e i t r e m a i n s an open q u e s t i o n whether s o c i a l i s o l a t i o n i s s t r e s s f u l i n t h e g e r b i l . The f o l l o w i n g e x p e r i m e n t was d e s i g n e d t o d e t e r m i n e (1) t h e e f f e c t s o f d i f f e r e n t i a l h o u s i n g on r e c e p t i v i t y , (2) p o t e n t i a l a d r e n a l m e d i a t i o n o f any o b s e r v e d e f f e c t s , and (3) any e f f e c t s o f a d r e n a l e c t o m y i t s e l f on s e x u a l r e c e p t i v i t y . Method C u l l e n & S c a r b o r o u g h (1970) f o u n d t h a t a d r e n a l e c t o m i z e d g e r b i l s r e q u i r e i n j e c t i o n s o f 1 mg h y d r o c o r t i s o n e a c e t a t e (HCA) i n a d d i t i o n t o a c c e s s t o a 0.9% s a l i n e d r i n k i n g s o l u t i o n f o r s u r v i v a l . HCA i s an e s t e r o f h y d r o c o r t i s o n e , a major s t e r o i d of t h e g e r b i l a d r e n a l ( O l i v e r & P e r o n , 1964). A p i l o t s t u d y i n our l a b o r a t o r y d e t e r m i n e d t h a t t h e HCA i n j e c t i o n s d i d not s i g n i f i c a n t l y a l t e r r e c e p t i v i t y i n a d r e n a l e c t o m i z e d g e r b i l s . I m m e d i a t e l y a f t e r s u r g e r y , s u b j e c t s were h o u s e d e i t h e r one a n i m a l p e r s i n g l e c a g e ( i s o l a t e d c o n d i t i o n ) o r t h r e e a n i m a l s p e r t r i p l e c a g e ( g r o u p e d c o n d i t i o n ) , k e e p i n g h o u s i n g d e n s i t y c o n s t a n t . T h i s h o u s i n g p r o c e d u r e was s i m i l a r t o t h a t u s e d by G o r z a l k a & R a i b l e (1981) and w o u l d t h u s a l l o w c o m p a r i s o n w i t h t h a t s t u d y . H a l f o f t h e s u b j e c t s i n e a c h h o u s i n g c o n d i t i o n r e c e i v e d b i l a t e r a l o v a r i e c t o m i e s and a d r e n a l e c t o m i e s w h i l e t h e r e m a i n d e r r e c e i v e d o v a r i e c t o m i e s and sham a d r e n a l e c t o m i e s . I n j e c t i o n s o f 1 mg HCA ( a d r e n a l e c t o m i z e d a n i m a l s ) and t h e v e h i c l e , Tween 80 and 0.9% s a l i n e ( o v a r i e c t o m i z e d a n i m a l s ) were i n i t i a t e d on t h e day of s u r g e r y and g i v e n e v e r y o t h e r day f o r t h e d u r a t i o n o f t h e e x p e r i m e n t . A d r e n a l e c t o m y f a c i l i t a t e s s e x u a l b e h a v i o u r i n t h e r a t 37 ( G r a y & G o r z a l k a , 1980) and has no e f f e c t i n t h e h a m s t e r ( C a r t e r , 1972). In a s p e c i e s as a d r e n a l d e p e n d e n t as t h e g e r b i l , a d r e n a l e c t o m y c o u l d be e i t h e r f a c i l i t a t o r y , i n h i b i t o r y , o r have no e f f e c t on r e c e p t i v i t y . T h e r e f o r e , a d o s e o f EB w h i c h would a l l o w d e t e c t i o n of i n c r e a s e d o r d e c r e a s e d s e x u a l r e s p o n d i n g was d e s i r e d . S i n c e e s t r o g e n was t o be a d m i n i s t e r e d c h r o n i c a l l y , t h e r e s u l t s of E x p e r i m e n t 4 i n d i c a t e d t h a t t h e 10 pq EB dose would be an a p p r o p r i a t e i n i t i a l d o s e . I f a n i m a l s r e a c h e d a s y m p t o t e a t low l e v e l s o f r e c e p t i v i t y , s u b s e q u e n t i n j e c t i o n s of 100 pq EB c o u l d be a d m i n i s t e r e d w h i l e a s y m p t o t e a t h i g h l e v e l s o f r e c e p t i v i t y w o u l d i n d i c a t e t h a t 1 ^ug EB i n j e c t i o n s s h o u l d i n s t e a d be a d m i n i s t e r e d . I n j e c t i o n s of 10 pq EB were a d m i n i s t e r e d d a i l y f o r 12 d a y s , w i t h t e s t i n g o c c u r r i n g on Days 5-12 o f 10 yq EB t r e a t m e n t . On Days 13-20, i n j e c t i o n s of 100 ^ug EB were a d m i n i s t e r e d i n an a t t e m p t t o i n c r e a s e t h e low l e v e l s o f r e s p o n d i n g e x h i b i t e d by t h e a d r e n a l e c t o m i z e d a n i m a l s . F i n a l l y , on Day 21, 500 ^jjg P was a d m i n i s t e r e d 3-4 h r p r i o r t o t e s t i n g i n a f i n a l a t t e m p t t o i n c r e a s e t h e l e v e l of s e x u a l r e s p o n d i n g i n a d r e n a l e c t o m i z e d a n i m a l s . R e s u l t s and D i s c u s s i o n D a t a from a n i m a l s t h a t d i e d d u r i n g t h e c o u r s e o f t h e e x p e r i m e n t were e l i m i n a t e d f r o m t h e a n a l y s i s . The r e s u l t i n g n's were 12 f o r g r o u p e d o v a r i e c t o m i z e d , 17 f o r i s o l a t e d o v a r i e c t o m i z e d , and 11 e a c h f o r g r o u p e d and i s o l a t e d a d r e n a l e c t o m i z e d a n i m a l s . An e x a m i n a t i o n o f t h e d a t a s u g g e s t e d t h a t , a l t h o u g h d i f f e r e n t i a l h o u s i n g d i d not a p p e a r t o have an e f f e c t , a d r e n a l e c t o m y d i d r e d u c e r e c e p t i v i t y ( F i g u r e 5 ) . 38 FIGURE 5. E f f e c t s o f a d r e n a l e c t o m y , h o u s i n g c o n d i t i o n , and dose of c h r o n i c a l l y a d m i n i s t e r e d e s t r o g e n on s e x u a l r e c e p t i v i t y i n f e m a l e g e r b i l s . R e c e p t i v i t y i s e x p r e s s e d a s t h e r a t i o o f l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . O v a r i e c t o m i z e d ( o vex) and o v a r i e c t o m i z e d -a d r e n a l e c t o m i z e d ( o v e x - a d r e x ) a n i m a l s were h o u s e d one p e r s i n g l e c a g e ( i s o l a t e d ) o r t h r e e p e r t r i p l e c a g e ( g r o u p e d ) . A n i m a l s r e c e i v e d d a i l y i n j e c t i o n s o f 10 yq e s t r a d i o l b e n z o a t e (EB) b e g i n n i n g on Day 1 and 100 ;jg EB b e g i n n i n g on Day 13. 500 jug p r o g e s t e r o n e (P) was a d m i n i s t e r e d 3-4 h r p r i o r t o t e s t i n g on Day 22. T e s t i n g o c c u r r e d on Days 5-22. 40 N e i t h e r t h e 10 j j g nor t h e 100 pq dose o f EB were s u f f i c i e n t t o r e s t o r e c o n t r o l l e v e l s o f r e c e p t i v i t y a l t h o u g h t h e 100 ^pg EB dose d i d a p p e a r t o r a i s e l e v e l s of r e c e p t i v i t y somewhat. In a d d i t i o n , a l t h o u g h P d i d f a c i l i t a t e s e x u a l r e s p o n d i n g i n a d r e n a l e c t o m i z e d a n i m a l s , l e v e l s of r e c e p t i v i t y s t i l l a p p e a r e d somewhat low f o r t h e d o s e s of hormones a d m i n i s t e r e d . A 2x2x2x8 r e p e a t e d measures w i t h n e s t e d f a c t o r s a n a l y s i s o f v a r i a n c e p e r f o r m e d on t h e EB d a t a r e v e a l e d s i g n i f i c a n t e f f e c t s o f s u r g e r y , F ( 1 , 4 7 ) = 102.64, 2 < 0.0001, and s u r g e r y by t e s t b l o c k (10 pg v s 100 pq E B ) , F ( 1 , 4 7 ) = 12.06, 2 = 0.0012. O t h e r s i g n i f i c a n t e f f e c t s r e v e a l e d by t h e a n a l y s i s o f v a r i a n c e , were t e s t b l o c k , F ( 1 , 4 7 ) = 86.00, p_ < 0.0001, h o u s i n g by t e s t , F (14,658) = 2.18, £ 0.0074, and s u r g e r y by t e s t , F (14,658) = 6.44, 2 < 0.0001. A t - t e s t was p e r f o r m e d on t h e P d a t a f o r o v a r i e c t o m i z e d v e r s u s a d r e n a l e c t o m i z e d a n i m a l s and r e v e a l e d t h a t a d r e n a l e c t o m i z e d a n i m a l s e x h i b i t e d s i g n i f i c a n t l y l o w e r r e c e p t i v i t y s c o r e s t h a n o v a r i e c t o m i z e d a n i m a l s , 2 < 0.05. S u b s e q u e n t Newman-Keul's a n a l y s e s on t h e e f f e c t o f s u r g e r y and of s u r g e r y by t e s t b l o c k r e v e a l e d t h a t , o v e r a l l , o v a r i e c t o m i z e d a n i m a l s were s i g n i f i c a n t l y more r e c e p t i v e t h a n a d r e n a l e c t o m i z e d a n i m a l s , 2 < 0.05. In a d d i t i o n , a l t h o u g h a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g 100 ^ug EB were s i g n i f i c a n t l y more r e c e p t i v e t h a n a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g 10 jjq EB, 2 < 0.05, b o t h of t h e s e g r o u p s were s i g n i f i c a n t l y l e s s r e c e p t i v e t h a n o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g 10 pq EB, 2 <0.05. The p r e s e n t r e s u l t s i n d i c a t e t h a t a d r e n a l e c t o m y d e c r e a s e s s e x u a l b e h a v i o u r i n o v a r i e c t o m i z e d a n i m a l s c h r o n i c a l l y a d m i n i s t e r e d EB. T h i s e f f e c t does n o t a p p e a r t o be due s o l e l y 41 t o a d e c r e a s e d s e n s i t i v i t y t o EB s i n c e i n c r e a s i n g t h e d o s e of EB a d m i n i s t e r e d t o a d r e n a l e c t o m i z e d a n i m a l s d i d n o t r e s u l t i n l e v e l s of r e c e p t i v i t y e q u i v a l e n t t o t h o s e of o v a r i e c t o m i z e d c o n t r o l s . In a d d i t i o n , a l t h o u g h P i n c r e a s e d r e c e p t i v i t y , i t d i d not e l i m i n a t e t h e d i f f e r e n c e between o v a r i e c t o m i z e d and a d r e n a l e c t o m i z e d a n i m a l s . The r e d u c t i o n i n r e c e p t i v i t y o b s e r v e d i n a d r e n a l e c t o m i z e d a n i m a l s c o u l d be due t o one o r more o f t h e f o l l o w i n g f a c t o r s : (1) a d r e n a l e c t o m i z e d g e r b i l s may be more dep e n d e n t upon t h e s y n e r g i s t i c a c t i o n s of P w i t h EB i n t h e i n d u c t i o n o f maximal r e c e p t i v i t y , (2) a d r e n a l e c t o m y may d e c r e a s e s e n s i t i v i t y t o P o r t o a m e t a b o l i t e o f P, (3) g e r b i l s may r e q u i r e one o r more a d r e n a l s t e r o i d s i n a d d i t i o n t o EB and P f o r t h e e l i c i t a t i o n o f maximal r e c e p t i v i t y , (4) a d r e n a l e c t o m y may have a n o n - s p e c i f i c d e b i l i t a t i n g e f f e c t . However, s i n c e s u b s t a n t i a l l y i n c r e a s i n g t h e d ose of' EB a d m i n i s t e r e d d i d n o t s i g n i f i c a n t l y a l t e r r e c e p t i v i t a y i n a d r e n a l e c t o m i z e d a n i m a l s , i t i s u n l i k e l y t h a t t h e d e c r e a s e i n r e c e p t i v i t y o b s e r v e d i n t h e s e a n i m a l s was due t o a d e c r e a s e d s e n s i t i v i t y t o EB. EXPERIMENT 6 E x p e r i m e n t 5 i n d i c a t e d t h a t a d r e n a l e c t o m y s i g n i f i c a n t l y r e d u c e d r e c e p t i v i t y i n g e r b i l s g i v e n c h r o n i c EB t r e a t m e n t . I t i s p o s s i b l e t h a t t h i s e f f e c t i s be due t o an i n c r e a s e d d ependence o r a d e c r e a s e d s e n s i t i v i t y t o some a c t i o n of P i n t h e e l i c i t a t i o n of maximal r e c e p t i v i t y i n a d r e n a l e c t o m i z e d g e r b i l s . T h i s e x p e r i m e n t was d e s i g n e d t o i n v e s t i g a t e t h e s e n s i t i v i t y o f a d r e n a l e c t o m i z e d g e r b i l s t o P and t o a m e t a b o l i t e o f P known t o i n d u c e r e c e p t i v i t y i n f e m a l e r a t s ( G o r z a l k a & Whalen, 1977; 42 Whalen & G o r z a l k a , 1972) and i n some mouse s t r a i n s ( G o r z a l k a & Whalen, 1974). Method Doses of 0.0, 0.1, 0.5, o r 1.0 mg P o r 1.0 mg d i h y d r o p r o g e s t e r o n e (DHP) were a d m i n i s t e r e d t o o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d a n i m a l s , c r e a t i n g a t o t a l o f t e n t r e a t m e n t g r o u p s . One week b e f o r e t h e f i r s t t e s t , a n i m a l s r e c e i v e d a p r i m i n g d o s e o f 10 pq EB i n a d d i t i o n t o t h e EB a d m i n i s t e r e d 48 and 24 h r p r i o r t o t e s t i n g . Due t o t h e s i z e o f t h e e x p e r i m e n t and l i m i t e d c o l o n y s p a c e , a c o u n t e r b a l a n c e d , r e p e a t e d - m e a s u r e s d e s i g n was e m p l o y e d . A n i m a l s were t e s t e d once e v e r y s e v e n d a y s w i t h a P v e h i c l e (EB o n l y ) t e s t o c c u r r i n g between e a c h P t e s t . P r e v i o u s work i n d i c a t e s t h a t t h e r e p e a t e d m e a sures d e s i g n i s n o t c o n f o u n d e d by r e s i d u a l h o r m o n a l e f f e c t s p r o v i d e d t e s t s a r e s e p a r a t e d by a week (Whalen & G o r z a l k a , 1972). E a c h a n i m a l t h u s r e c e i v e d e a c h of t h e t h r e e P d o s e s and t h e DHP p l u s f o u r t e s t s w i t h EB o n l y , r e s u l t i n g i n a t o t a l o f e i g h t t e s t s . HCA and v e h i c l e ( p e a n u t o i l ) i n j e c t i o n s were c a r r i e d o ut as s t a t e d i n E x p e r i m e n t 5. R e s u l t s and D i s c u s s i o n D a t a from a n i m a l s d y i n g d u r i n g t h e c o u r s e o f t h e e x p e r i m e n t were e l i m i n a t e d from t h e a n a l y s i s , r e s u l t i n g i n n's of 12 f o r a l l o v a r i e c t o m i z e d g r o u p s and 20 f o r a l l a d r e n a l e c t o m i z e d g r o u p s . An e x a m i n a t i o n of t h e d a t a i n d i c a t e d t h a t a d r e n a l e c t o m y a g a i n p r o d u c e d a d e c r e a s e i n s e x u a l r e c e p t i v i t y . F u r t h e r m o r e , even t h e 1 mg d o s e o f P d i d not r a i s e t h e l e v e l o f r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i a m l s t o t h a t e x h i b i t e d by o v a r i e c t o m i z e d c o n t r o l s ( F i g u r e 6 ) . In a d d i t i o n , r e l a t i v e t o t h e e f f e c t 43 FIGURE 6. S e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s d o s e s o f p r o g e s t e r o n e . R e c e p t i v i t y i s e x p r e s s e d as t h e r a t i o of l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . O v a r i e c t o m i z e d (ovex) and o v a r i e c t o m i z e d -a d r e n a l e c t o m i z e d ( o v e x - a d r e x ) a n i m a l s were a d m i n i s t e r e d 10 j j g e s t r a d i o l b e n z o a t e 48 and 24 h r b e f o r e t e s t i n g and 0.0, 0.1, 0.5, o r 1.0 mg p r o g e s t e r o n e o r 1 mg d i h y d r o p r o g e s t e r o n e (DHP) 3-4 hr p r i o r t o t e s t i n g . 45 p r o d u c e d by even 0.1 mg P i n o v a r i e c t o m i z e d a n i m a l s , 1.0 mg DHP was r e l a t i v e l y i n e f f e c t i v e i n s t i m u l a t i n g r e c e p t i v i t y i n o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d a n i m a l s . A 2x5 r e p e a t e d m e asures a n a l y s i s o f v a r i a n c e p e r f o r m e d on t h e d a t a i n d i c a t e d s i g n i f i c a n t e f f e c t s o f s u r g e r y , F (1,30) = 65.78, p < 0.0001, d o s e , F ( 4 , 1 2 0 ) = 30.85, p_ < 0.0001, and s u r g e r y by d o s e , F ( 4 , 1 2 0 ) = 6.89, p_ < 0.0001. S u b s e q u e n t Newman-Keul's a n a l y s e s p e r f o r m e d on t h e s i g n i f i c a n t i n t e r a c t i o n e f f e c t i n d i c a t e d t h a t t h e o n l y c o n d i t i o n s i n w h i c h o v a r i e c t o m i z e d a n i m a l s and a d r e n a l e c t o m i z e d a n i m a l s d i d not d i f f e r s i g n i f i c a n t l y were t h e o i l and DHP c o n d i t i o n s . F u r t h e r m o r e , a l t h o u g h a d r e n a l e c t o m i z e d a n i m a l s g i v e n 0.5 and 1.0 mg P were s i g n i f i c a n t l y more r e c e p t i v e t h a n o i l t r e a t e d o v a r i e c t o m i z e d a n i m a l s , p_ < 0.05, t h e y were s i g n i f i c a n t l y l e s s r e c e p t i v e t h a n o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g a s l i t t l e a s 0.1 mg P, £ < 0.05. The r e s u l t s o f t h e p r e s e n t e x p e r i m e n t i n d i c a t e t h a t even r e l a t i v e l y h i g h d o s e s o f P g i v e n i n c o n j u n c t i o n w i t h EB a r e n o t s u f f i c i e n t t o r a i s e l e v e l s o f r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s t o t h o s e e x h i b i t e d by o v a r i e c t o m i z e d c o n t r o l s . I t seems i m p r o b a b l e t h a t t h e r e d u c e d l e v e l s of r e c e p t i v i t y o b s e r v e d i n a d r e n a l e c t o m i z e d a n i m a l s a r e due s o l e l y t o a r e d u c e d s e n s i t i v i t y t o P o r an i n c r e a s e d d e p endence on t h e s y n e r g i s t i c a c t i o n o f P w i t h EB. Even when g i v e n 10 t i m e s t h e amount r e c e i v e d by o v a r i e c t o m i z e d a n i m a l s (0.1 v s 1.0 mg), a d r e n a l e c t o m i z e d a n i m a l s r e m a i n e d s i g n i f i c a n t l y l o w e r i n t h e i r r e c e p t i v i t y . T h u s , i t seems more p l a u s i b l e t h a t o v a r i a n s t e r o i d s a l o n e may n o t be s u f f i c i e n t t o . i n d u c e maximal r e c e p t i v i t y and t h a t a d r e n a l s t e r o i d s p l a y some r o l e i n t h e 46 m e d i a t i o n o f s e x u a l r e c e p t i v i t y i n t h e f e m a l e g e r b i l . EXPERIMENT 7 E x p e r i m e n t s 5 and 6 i n d i c a t e d t h a t t h e r e d u c e d l e v e l s of r e c e p t i v i t y o b s e r v e d i n a d r e n a l e c t o m i z e d a n i m a l s were not due s o l e l y t o r e d u c e d s e n s i t i v i t y t o o v a r i a n hormones, t h o u g h t h i s may be one f a c t o r . T h i s s u g g e s t s t h a t e i t h e r a d r e n a l e c t o m y has a g e n e r a l d e b i l i t a t i n g e f f e c t o r t h a t p e r h a p s a d r e n a l s t e r o i d s a r e i n some way n o r m a l l y i n v o l v e d i n t h e r e g u l a t i o n of s e x u a l r e c e p t i v i t y i n t h e f e m a l e g e r b i l . The h e a l t h of a d r e n a l e c t o m i z e d g e r b i l s may be r e l a t e d t o t h e sodium r e t e n t i o n a n d / o r g l y c o g e n d e p o s i t i o n p r o p e r t i e s o f t h e a d r e n a l s t e r o i d a d m i n i s t e r e d t o m a i n t a i n l i f e . I n a d r e n a l e c t o m i z e d r a t s , i t has been f o u n d t h a t h y d r o c o r t i s o n e ( C o r t i s o l ) i s a b o u t 50% more e f f e c t i v e t h a n c o r t i s o n e f o r s o d ium r e t e n t i o n and g l y c o g e n d e p o s i t i o n , t h o u g h b o t h a r e c o n s i d e r e d t o be p r i m a r i l y g l u c o c o r t i c o i d s . D e o x y c o r t i c o s t e r o n e , on t h e o t h e r hand, i s a b o u t 300 t i m e s as e f f e c t i v e as c o r t i s o n e i n i t s sodium r e t e n t i o n a b i l i t i e s b u t w i l l n ot m a i n t a i n g l y c o g e n d e p o s i t i o n ( L i d d l e & Melmon, 1974). C u l l e n & S c a r b o r o u g h (1970) f o u n d t h a t HCA was f a i r l y e f f e c t i v e i n m a i n t a i n i n g a d r e n a l e c t o m i z e d g e r b i l s w h i l e d e o x y c o r t i c o s t e r o n e a c e t a t e (DOCA) was n o t . H y d r o c o r t i s o n e i s a major a d r e n a l s t e r o i d o f t h e g e r b i l and, g i v e n i t s m i n e r a l c o r t i c o i d and g l u c o c o r t i c o i d p r o p e r t i e s , i t i s p e r h a p s not s u r p r i s i n g t h a t i t i s t h e most e f f e c t i v e a d r e n a l s t e r o i d f o r m a i n t e n a n c e o f a d r e n a l e c t o m i z e d g e r b i l s . DOCA, on t h e o t h e r hand, has no g l u c o c o r t i c o i d p r o p e r t i e s and would n o t be e x p e c t e d 47 t o be as e f f e c t i v e a s HCA. C o r t i s o n e a c e t a t e (CA) has b o t h m i n e r a l c o r t i c o i d and g l u c o c o r t i c o i d p r o p e r t i e s b u t i s l e s s e f f e c t i v e t h a n HCA i n i t s a c t i o n and t h u s may not be v e r y e f f e c t i v e i n m a i n t a i n i n g a d r e n a l e c t o m i z e d g e r b i l s . T hus, i f t h e d e c r e a s e d r e c e p t i v i t y o b s e r v e d i n a d r e n a l e c t o m i z e d g e r b i l s i s a r e s u l t o f p o o r h e a l t h due t o l a c k o f s u f f i c i e n t g l u c o c o r t i c o i d s and m i n e r a l c o r t i c o i d s , r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g DOCA o r even CA s h o u l d be l o w e r t h a n r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g HCA s i n c e t h e f o r m e r s t e r o i d s a r e l e s s e f f e c t i v e t h a n t h e l a t t e r . I t i s a l s o p o s s i b l e , however, t h a t a g i v e n a d r e n a l s t e r o i d may p l a y a r o l e i n s e x u a l r e c e p t i v i t y , e i t h e r by f a c i l i t a t i n g r e c e p t i v i t y , i n h i b i t i n g r e c e p t i v i t y , o r by b e i n g a r e q u i r e m e n t , i n a d d i t i o n t o EB and P, f o r maximal r e c e p t i v i t y . A d r e n a l s t e r o i d s have been f o u n d t o i n f l u e n c e r e c e p t i v i t y i n f e m a l e r a t s u n der c e r t a i n c o n d i t i o n s . F o r example, c o r t i c o s t e r o n e e l i m i n a t e s t h e a d r e n a l e c t o m y - f a c i l i t a t i o n e f f e c t o b s e r v e d i n f e m a l e r a t s ( d e C a t a n z a r o e t a l . , 1981). On t h e o t h e r hand, DOCA f a c i l i t a t e s s e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d , E B - p r i m e d r a t s ( G o r z a l k a & Whalen, 1977). A f a c i l i t a t i n g o r i n h i b i t i n g e f f e c t o f a g i v e n a d r e n a l s t e r o i d c o u l d mask, o r be masked by, t h e h e a l t h p r o m o t i n g e f f e c t s o f t h a t s t e r o i d i n a d r e n a l e c t o m i z e d a n i m a l s . F o r example, i f DOCA e l i m i n a t e d t h e a d r e n a l e c t o m y -i n d u c e d d e c r e a s e i n r e c e p t i v i t y s e e n i n g e r b i l s , i t c o u l d be due t o a d i r e c t f a c i l i t a t i n g e f f e c t o f DOCA on r e c e p t i v i t y , a d i r e c t e f f e c t o f DOCA on h e a l t h w h i c h i n d i r e c t l y i n c r e a s e d r e c e p t i v i t y , o r b o t h . The use o f o v a r i e c t o m i z e d a s w e l l a s a d r e n a l e c t o m i z e d a n i m a l s would r e d u c e o r e l i m i n a t e t h i s d i f f i c u l t y by a l l o w i n g 48 t h e e f f e c t s of a d r e n a l s t e r o i d s on r e c e p t i v i t y t o be d e t e r m i n e d i n a d r e n a l l y - i n t a c t a n i m a l s . The p r e s e n t e x p e r i m e n t was d e s i g n e d t o i n v e s t i g a t e t h e p o s s i b i l i t y t h a t t h e r e d u c t i o n i n r e c e p t i v i t y o b s e r v e d i n a d r e n a l e c t o m i z e d g e r b i l s c o u l d be due t o a n o n - s p e c i f i c d e b i l i t a t i n g e f f e c t of a d r e n a l e c t o m y o r an e x t r a o v a r i a n d e p endence on some a d r e n a l s t e r o i d f o r t h e e l i c i t a t i o n of maximal r e c e p t i v i t y . In a d d i t i o n , t h e g e n e r a l e f f e c t s o f t h e s t e r o i d s on s e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d a n i m a l s w i l l be i n v e s t i g a t e d t o h e l p c o n t r o l f o r t h e p o s s i b i l i t y o f f a c i l i t a t o r y o r i n h i b i t o r y e f f e c t s . Method A l l a d r e n a l s t e r o i d i n j e c t i o n s (HCA, DOCA, o r CA) were g i v e n e v e r y o t h e r day i n d o s e s o f 1 mg, s t a r t i n g on t h e day of s u r g e r y . O v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d a n i m a l s r e c e i v e d i n j e c t i o n s o f one o f t h e s t e r o i d s . In a d d i t i o n , one g r o u p of o v a r i e c t o m i z e d a n i m a l s r e c e i v e d i n j e c t i o n s of t h e v e h i c l e (Tween 80 and 0.9% s a l i n e ) . A f t e r a p o s t o p e r a t i v e r e c o v e r y p e r i o d , a n i m a l s began r e c e i v i n g d a i l y s u b c u t a n e o u s i n j e c t i o n s of 10 ^ ug EB. The f i r s t t e s t of s e x u a l r e c e p t i v i t y o c c u r r e d on Day 9 of EB t r e a t m e n t when, a c c o r d i n g t o t h e r e s u l t s o f E x p e r i m e n t 4, o v a r i e c t o m i z e d a n i m a l s would be n e a r t h e i r maximal l e v e l of r e s p o n d i n g f o r t h e 10 j j g d o s e . On t h e f o l l o w i n g day, a n i m a l s were g i v e n 100 ^ug P 3-4 h r p r i o r t o t e s t i n g . R e s u l t s and D i s c u s i o n CA was f o u n d t o be i n c a p a b l e o f s u s t a i n i n g l i f e i n a d r e n a l e c t o m i z e d g e r b i l s and t h u s , t h a t g r o u p was e l i m i n a t e d 49 from t h e d a t a a n a l y s i s . The f i n a l number of a n i m a l s p e r g r o u p was 10 f o r o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g HCA, CA, and v e h i c l e i n j e c t i o n s and f o r a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g HCA i n j e c t i o n s , 22 f o r o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g DOCA i n j e c t i o n s , and 32 f o r a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g DOCA i n j e c t i o n s . The r e s u l t s o f t h e p r e s e n t e x p e r i m e n t s u g g e s t t h a t t h e r e was an o v e r a l l d e c r e a s e i n r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s . F u r t h e r m o r e , no a d r e n a l s t e r o i d g i v e n a l o n e a p p e a r e d c a p a b l e of r a i s i n g r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s t o l e v e l s e x h i b i t e d by c o n t r o l s , r e g a r d l e s s o f t h e p r e s e n c e or a b s e n c e o f P ( F i g u r e 7 ) . Due t o t h e n e s t e d n a t u r e o f t h e d e s i g n and t h e n e c e s s a r i l y m i s s i n g b l o c k s ( a d r e n a l e c t o m i z e d v e h i c l e and C A ) , a two way a n a l y s i s of v a r i a n c e ( g r o u p and t e s t ) was p e r f o r m e d on t h e d a t a . The a n a l y s i s r e v e a l e d s i g n i f i c a n t e f f e c t s of g r o u p , F (5,88) = 21.63, p_ < 0.0001, t e s t ( p r e - p r o g e s t e r o n e v e r s u s p o s t -p r o g e s t e r o n e ) , F ( 1 , 8 8 ) = 177.87, g < 0.0001, and g r o u p by t e s t , F ( 5 , 8 8 ) = 8.85, p < 0.0001. S u b s e q u e n t Newman-Keul's a n a l y s e s (c*= 0.05) were p e r f o r m e d on e a c h of t h e s e e f f e c t s . I t was f o u n d t h a t , o v e r a l l ( i . e . i n d e p e n d e n t o f t e s t ) , b o t h a d r e n a l e c t o m i z e d g r o u p s (HCA and DOCA) had s i g n i f i c a n t l y l o w e r r e c e p t i v i t y s c o r e s t h a n a l l o v a r i e c t o m i z e d g r o u p s . None o f t h e o v a r i e c t o m i z e d g r o u p s r e c e i v i n g a d r e n a l s t e r o i d s d i f f e r e d f r o m t h e v e h i c l e g r o u p . The g r o u p by t e s t a n a l y s i s i n d i c a t e d t h a t , a l t h o u g h none o f t h e g r o u p s d i f f e r e d s i g n i f i c a n t l y f r o m t h e v e h i c l e g r o u p d u r i n g t h e EB t e s t , s c o r e s o f b o t h of t h e a d r e n a l e c t o m i z e d g r o u p s were s i g n i f i c a n t l y l o w e r t h a n t h o s e o f 50 FIGURE 7. S e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d f e m a l e g e r b i l s a d m i n i s t e r e d a d r e n a l s t e r o i d s . R e c e p t i v i t y i s e x p r e s s e d as t h e r a t i o of l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . O v a r i e c t o m i z e d (ovex) and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d ( o v e x - a d r e x ) a n i m a l s were c h r o n i c a l l y a d m i n i s t e r e d h y d r o c o r t i s o n e a c e t a t e (HCA), d e o x y c o r t i c o s t e r o n e a c t e t a t e (DOCA), c o r t i s o n e a c e t a t e ( C A ) , o r t h e v e h i c l e ( V e ) . 10 ^ ug e s t r a d i o l b e n z o a t e (EB) was a d m i n i s t e r e d f o r 9 d a y s , w i t h t e s t i n g o c c u r r i n g on Day 9. On t h e f o l l o w i n g day, a n i m a l s r e c e i v e d 100 j j g p r o g e s t e r o n e (P) 3-4 h r p r i o r t o t e s t i n g . ioo H EB =ovex 80 | |=ovex-adrex„ 60 H 40 H 20 OH Ve HCA DOCA EB+P Ve HCA DOCA 52 t h e o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g a d r e n a l s t e r o i d s on t h e p o s t - p r o g e s t e r o n e t e s t . T h i s s u g g e s t s t h a t a d r e n a l e c t o m i z e d g e r b i l s a r e l e s s s e n s i t i v e t h a n o v a r i e c t o m i z e d a n i m a l s t o t h e s y n e r g i s t i c a c t i o n o f P w i t h EB. F u r t h e r m o r e , a l t h o u g h a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g HCA d i d n o t d i f f e r f r o m o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g t h e same t r e a t m e n t i n t h e p r e -p r o g e s t e r o n e t e s t , a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g DOCA were s i g n i f i c a n t l y l e s s r e c e p t i v e t h a n o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g s i m i l a r t r e a t m e n t . T h i s e f f e c t w ould a p p e a r t o be due t o t h e n o n - s i g n i f i c a n t f a c i l i t a t i o n o f r e c e p t i v i t y o b s e r v e d i n o v a r i e c t o m i z e d a n i m a l s r a t h e r t h a n an i n h i b i t i n g e f f e c t o f DOCA on r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s . The p r e s e n t r e s u l t s i n d i c a t e t h a t , o v e r a l l , n e i t h e r HCA nor DOCA, when a d m i n i s t e r e d a l o n e , i s s u f f i c i e n t t o r e s t o r e r e c e p t i v i t y i n a d r e n a l e c t o m i z e d g e r b i l s t o l e v e l s e x h i b i t e d by o v a r i e c t o m i z e d c o n t r o l s . However, i n p r e - p r o g e s t e r o n e t e s t s , a d r e n a l e c t o m i z e d a n i m a l s e x h i b i t l o w e r , b u t not s i g n i f i c a n t l y l o w e r , l e v e l s o f r e c e p t i v i t y . The s c o r e s of t h e a d r e n a l e c t o m i z e d a n i m a l s d u r i n g p o s t - p r o g e s t e r o n e t e s t s a p p e a r t o be t h e p r i m a r y c o n t r i b u t o r s t o t h e o v e r a l l s i g n i f i c a n c e o f t h e a d r e n a l e c t o m y e f f e c t . T h e s e r e s u l t s s u g g e s t t h a t a t l e a s t p a r t o f t h e d e c r e a s e i n r e s p o n d i n g i n a d r e n a l e c t o m i z e d a n i m a l s may be due t o a d e c r e a s e d s e n s i t i v i t y t o t h e s y n e r g i s t i c a c t i o n o f P w i t h EB. I t i s p o s s i b l e t h a t some c o m b i n a t i o n of a d r e n a l s t e r o i d s may enhance t h e a c t i o n o f P w i t h EB o r a d r e n a l s t e r o i d s p e r se may f a c i l i t a t e r e c e p t i v i t y i n a n i m a l s t r e a t e d w i t h e i t h e r EB o r EB p l u s P. 53 EXPERIMENT 8 E x p e r i m e n t 7 i n d i c a t e d t h a t no s i n g l e a d r e n a l s t e r o i d was c a p a b l e of r e s t o r i n g r e c e p t i v i t y o f a d r e n a l e c t o m i z e d a n i m a l s t o t h o s e l e v e l s e x h i b i t e d by c o n t r o l s . However, b e c a u s e e a c h a d r e n a l s t e r o i d a c t s p r i m a r i l y a s a g l u c o c o r t i c o i d or a m i n e r a l c o r t i c o i d , i t i s p o s s i b l e t h a t a c o m b i n a t i o n of s t e r o i d s i s n e c e s s a r y . I f a c o m b i n a t i o n o f an a d r e n a l m i n e r a l c o r t i c o i d and a g l u c o c o r t i c o i d does n o t r e s t o r e r e c e p t i v i t y t o c o n t r o l l e v e l s i n a d r e n a l e c t o m i z e d a n i m a l s , one c o u l d assume r e d u c e d r e c e p t i v i t y i s e i t h e r due t o (1) a l a c k of some o t h e r a d r e n a l s e c r e t i o n i n v o l v e d i n r e c e p t i v i t y , (2) an e x c e s s of some p i t u i t a r y s e c r e t i o n , o r (3) a n o n s p e c i f i c d e b i l i t a t i n g e f f e c t of a d r e n a l e c t o m y . However, i f a c o m b i n a t i o n of a d r e n a l s t e r o i d s d o e s r e s t o r e o v e r a l l l e v e l s o f r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s , i t would s u g g e s t t h a t t h e f e m a l e g e r b i l , u n l i k e o t h e r f e m a l e r o d e n t s , i s d e p e n d e n t upon b o t h a d r e n a l s t e r o i d s and EB and P f o r t h e i n d u c t i o n o f maximal r e c e p t i v i t y . Method The p r o c e d u r e s o u t l i n e d i n E x p e r i m e n t 7 were f o l l o w e d w i t h t h e e x c e p t i o n of t h e a d r e n a l s t e r o i d s a d m i n i s t e r e d . O v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d a n i m a l s r e c e i v e d e i t h e r 1 mg HCA + 1 mg DOCA, 1 mg HCA + 1 mg CA, o r 1 mg DOCA + 1 mg CA. Thus, t h e HCA + CA g r o u p was a d m i n i s t e r e d two m i n e r a l c o r t i c o i d s w h i l e t h e o t h e r s r e c e i v e d b o t h a m i n e r a l c o r t i c o i d and a g l u c o c o r t i c o i d . As i n E x p e r i m e n t 7, t h e r e was a l s o an o v e r i e c t o m i z e d c o n t r o l g r o u p w h i c h r e c e i v e d i n j e c t i o n s o f t h e v e h i c l e , r e s u l t i n g i n a t o t a l of s e v e n g r o u p s ( f o u r o v a r i e c t o m i z e d , t h r e e o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d ) . 54 R e s u l t s and D i s c u s s i o n D a t a from a n i m a l s n ot c o m p l e t i n g b o t h t e s t s were e l i m i n a t e d from t h e a n a l y s i s . The r e s u l t i n g number of a n i m a l s p e r g r o u p was 10 f o r o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g HCA + DOCA, DOCA + CA, and v e h i c l e i n j e c t i o n s , 16 f o r o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g HCA + CA, 12 f o r a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g HCA + CA, 14 f o r a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g HCA + DOCA, and 17 f o r a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g DOCA + CA. An e x a m i n a t i o n o f t h e d a t a s u g g e s t s t h a t , once a g a i n , a d r e n a l e c t o m y p r o d u c e d an o v e r a l l d e c r e a s e i n s e x u a l r e s p o n d i n g . Y e t , a t l e a s t d u r i n g t h e p r e - p r o g e s t e r o n e t e s t , a l l s t e r o i d t r e a t m e n t s a p p e a r e d e f f e c t i v e i n r e s t o r i n g r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s t o c o n t r o l l e v e l s ( F i g u r e 8 ) . However, d u r i n g t h e p o s t - p r o g e s t e r o n e t e s t , a d r e n a l e c t o m i z e d a n i m a l s g i v e n HCA + CA r e m a i n e d l e s s r e c e p t i v e t h a n o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g t h e same t r e a t m e n t . T h i s d i d n o t a p p e a r t o be t h e c a s e i n g r o u p s where a n i m a l s were r e c e i v i n g b o t h a g l u c o c o r t i c o i d and a m i n e r a l c o r t i c o i d . F i n a l l y , i t a p p e a r e d t h a t , a t l e a s t i n t h e p r e - p r o g e s t e r o n e t e s t , o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g DOCA + HCA e x h i b i t e d an i n c r e a s e i n r e c e p t i v i t y beyond t h a t e x h i b i t e d by v e h i c l e c o n t r o l s . To be c o n s i s t e n t w i t h t h e a n a l y s i s p e r f o r m e d i n E x p e r i m e n t 7, a two-way a n a l y s i s o f v a r i a n c e was p e r f o r m e d on t h e d a t a . T h i s a n a l y s i s r e v e a l e d s i g n i f i c a n t e f f e c t s o f g r o u p , F ( 6 , 8 2 ) = 7.92, p_ < 0.0001, t e s t , F ( 1 , 8 2 ) = 83.50, 2 < 0.0001, and g r o u p by t e s t , F ( 6 , 8 2 ) = 2.57, 2 = 0.025. Newman-Keul's p r o c e d u r e s were s u b s e q u e n t l y p e r f o r m e d on e a c h o f t h e s e e f f e c t s (c*= 0.05). An a n a l y s i s o f t h e o v e r a l l e f f e c t of g r o u p r e v e a l e d 55 FIGURE 8. S e x u a l r e c e p t i v i t y i n o v a r i e c t o m i z e d and o v a r i e c t o m i z e d - a d r e n a l e c t o m i z e d f e m a l e g e r b i l s a d m i n i s t e r e d v a r i o u s c o m b i n a t i o n s o f a d r e n a l s t e r o i d s . R e c e p t i v i t y i s e x p r e s s e d as t h e r a t i o o f l o r d o s i s r e s p o n s e s t o mounts w i t h p e l v i c t h r u s t i n g . O v a r i e c t o m i z e d ( o vex) and o v a r i e c t o m i z e d -a d r e n a l e c t o m i z e d ( o v e x - a d r e x ) a n i m a l s were c h r o n i c a l l y a d m i n i s t e r e d h y d r o c o r t i s o n e a c e t a t e and c o r t i s o n e a c e t a t e (HCA+CA), d e o x y c o r t i c o s t e r o n e a c e t a t e and c o r t i s o n e a c e t a t e (DOCA+CA), d e o x y c o r t i c o s t e r o n e a c e t a t e and h y d r o c o r t i s o n e a c e t a t e (DOCA+HCA), o r t h e v e h i c l e ( V e ) . 10 pq e s t r a d i o l b e n z o a t e (EB) was a d m i n i s t e r e d f o r 9 d a y s , w i t h t e s t i n g o c c u r r i n g on Day 9. On t h e f o l l o w i n g day, a n i m a l s r e c e i v e d 100 ^ug p r o g e s t e r o n e (P) 3-4 hr p r i o r t o t e s t i n g . 56 i £ 5 < Q x o + < o o Q o + O CL + GQ|- 3 5 < X CD i — T3 CO X X CD CD > > O o II II CD LU < ° + < o o Q o + O I o o o 00 I o CO T o o CM •f o 001- x iuno|Aj/sjsopjo-i 57 t h a t o n l y t h e a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g HCA + CA, two m i n e r a l c o r t i c o i d s , were s i g n i f i c a n t l y l e s s r e c e p t i v e t h a n o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g v e h i c l e i n j e c t i o n s . E x a m i n a t i o n o f t h e g r o u p s by t e s t i n t e r a c t i o n r e v e a l e d t h a t , f o r t h e p r e - p r o g e s t e r o n e t e s t , o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g DOCA + HCA were s i g n i f i c a n t l y more r e c e p t i v e t h a n c o n t r o l a n i m a l s . T h i s e f f e c t was n o t o b s e r v e d i n t h e p o s t - p r o g e s t e r o n e t e s t , p r e s u m a b l y b e c a u s e o f a c e i l i n g e f f e c t ( i . e . , DOCA + HCA a n i m a l s n e a r e d t h e maximum LQ i n t h e p r e - p r o g e s t e r o n e t e s t ) . The o n l y o t h e r g r o u p f o u n d t o d i f f e r s i g n i f i c a n t l y from o v a r i e c t o m i z e d a n i m a l s r e c e i v i n g v e h i c l e i n j e c t i o n s , was t h e a d r e n a l e c t o m i z e d HCA + CA g r o u p , w h i c h was s i g n i f i c a n t l y l e s s r e c e p t i v e t h a n v e h i c l e c o n t r o l s d u r i n g t h e p o s t - p r o g e s t e r o n e t e s t . Due t o t h e o b s e r v e d f a c i l i t a t i o n e f f e c t o f HCA + DOCA and t h e n e c e s s a r y l a c k o f a v e h i c l e c o n t r o l g r o u p i n a d r e n a l e c t o m i z e d a n i m a l s , i t a l s o seemed a p p r o p r i a t e t o compare t h e e f f e c t i v e n e s s o f v a r i o u s s t e r o i d c o m b i n a t i o n s i n a d r e n a l e c t o m i z e d a n i m a l s and a l s o w i t h t h o s e o f o v a r i e c t o m i z e d a n i m a l s . O v e r a l l , i t was f o u n d t h a t a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g DOCA + HCA were s i g n i f i c a n t l y more r e c e p t i v e t h a n t h e r e m a i n i n g two a d r e n a l e c t o m i z e d g r o u p s w h i c h d i d n o t d i f f e r from e a c h o t h e r . In a d d i t i o n , n e i t h e r o f t h e a d r e n a l e c t o m i z e d g r o u p s r e c e i v i n g DOCA d i f e r e d s i g n i f i c a n t l y from t h e o v a r i e c t o m i z e d g r o u p s r e c e i v i n g a s i m i l a r t r e a t m e n t w h i l e a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g t h e two m i n e r a l c o r t i c o i d s r e m a i n e d s i g n i f i c a n t l y l e s s r e c e p t i v e t h a n t h e c o r r e s p o n d i n g o v a r i e c t o m i z e d g r o u p . 58 Th e s e r e s u l t s s u g g e s t t h a t t h e a d m i n i s t r a t i o n o f a g l u c o c o r t i c o i d p l u s a m i n e r a l c o r t i c o i d i s s u f f i c i e n t , and p e r h a p s n e c e s s a r y , t o r a i s e t h e l e v e l of s e x u a l r e s p o n d i n g o b s e r v e d i n a d r e n a l e c t o m i z e d g e r b i l s t o t h a t e x h i b i t e d by c o n t r o l a n i m a l s . F u r t h e r m o r e , a l t h o u g h DOCA + CA r e s t o r e d r e c e p t i v i t y t o l e v e l s e x h i b i t e d by c o n t r o l s , DOCA + HCA was s i g n i f i c a n t l y more e f f e c t i v e , p e r h a p s b e c a u s e of a d i r e c t f a c i l i t a t o r y e f f e c t on s e x u a l r e s p o n d i n g . I f one compares t h e p e r f o r m a n c e o f a g i v e n g r o u p d u r i n g t h e p r e - and p o s t - p r o g e s t e r o n e t e s t s , i t becomes a p p a r e n t t h a t , f o r a l l o v a r i e c t o m i z e d g r o u p s ( e x c e p t t h e DOCA + HCA g r o u p w h i c h was a l r e a d y a t a h i g h l e v e l of s e x u a l r e s p o n d i n g ) , s c o r e s d u r i n g t h e p o s t - t e s t t e s t were s i g n i f i c a n t l y g r e a t e r t h a n d u r i n g t h e p r e -p r o g e s t e r o n e t e s t . T h i s i s not t h e c a s e f o r any of t h e t h r e e a d r e n a l e c t o m i z e d g r o u p s . To d e t e r m i n e t h e e x a c t n a t u r e of t h i s e f f e c t , a 2x2x4 a n a l y s i s o f v a r i a n c e w i t h n e s t e d f a c t o r s was p e r f o r m e d on t h e d a t a . T h i s a n a l y s i s r e v e a l e d a s i g n i f i c a n t s u r g e r y by t e s t i n t e r a c t i o n , F ( 1 , 8 2 ) = 6.54, p_ = 0.012. A Newman-Keul's a n a l y s i s i n d i c a t e d t h a t , o v e r a l l , l e v e l s of r e c e p t i v i t y e x h i b i t e d by o v a r i e c t o m i z e d a n i m a l s were s i m i l a r t o t h o s e e x h i b i t e d by a d r e n a l e c t o m i z e d a n i m a l s d u r i n g t h e p r e -p r o g e s t e r o n e t e s t but were s i g n i f i c a n t l y g r e a t e r d u r i n g t h e p o s t - p r o g e s t e r o n e t e s t (c*- = 0 . 0 5 ) . T h u s , f o r any g i v e n t r e a t m e n t , a d r e n a l e c t o m i z e d a n i m a l s g i v e n EB p l u s P do not d i f f e r f r o m o v a r i e c t o m i z e d a n i m a l s . However, o v e r a l l , a d r e n a l e c t o m i z e d a n i m a l s were s i g n i f i c a n t l y l e s s r e c e p t i v e t h a n o v a r i e c t o m i z e d a n i m a l s when g i v e n EB p l u s P. T h i s s u g g e s t s t h a t a t l e a s t p a r t o f t h e a d r e n a l e c t o m y e f f e c t i s due t o a d e c r e a s e d 59 l e v e l o f r e s p o n d i n g t o P o r t o a r e d u c e d s y n e r g i s m w i t h EB r a t h e r t h a n b e i n g due s o l e l y t o p o o r h e a l t h . Thus, i t would a p p e a r t h a t , even when g i v e n a d r e n a l g l u c o c o r t i c o i d s and m i n e r a l c o r t i c o i d s , a d r e n a l e c t o m i z e d a n i m a l s s t i l l e x h i b i t some d i f f e r e n c e s i n r e s p o n d i n g when compared t o o v a r i e c t o m i z e d a n i m a l s . T h i s d i f f e r e n c e a p p e a r s t o be due t o a r e d u c e d r e s p o n d i n g t o t h e e f f e c t s o f P when g i v e n i n c o n j u n c t i o n w i t h EB r a t h e r t h a n t o a g e n e r a l r e d u c t i o n i n r e s p o n s i v i t y t o e s t r o g e n . In a d d i t i o n , a g e n e r a l i z e d d e b i l i t a t i n g e f f e c t o f a d r e n a l e c t o m y d o e s not a p p e a r t o be r e s p o n s i b l e f o r t h e d e c r e a s e d r e s p o n d i n g i n a d r e n a l e c t o m i z e d a n i m a l s s i n c e t h e y d i d n o t d i f f e r from o v a r i e c t o m i z e d a n i m a l s d u r i n g t h e p r e - p r o g e s t e r o n e t e s t . GENERAL DISCUSSION The r e s u l t s o f E x p e r i m e n t 5 i n d i c a t e t h a t , a l t h o u g h h o u s i n g has no s i g n i f i c a n t e f f e c t on s e x u a l r e c e p t i v i t y i n t h e f e m a l e g e r b i l , a d r e n a l e c t o m y s i g n i f i c a n t l y d e c r e a s e d r e c e p t i v i t y . I n i t i a l l y , i t was s u g g e s t e d t h a t t h i s d e c l i n e c o u l d be due t o one o r more o f t h e f o l l o w i n g e f f e c t s o f a d r e n a l e c t o m y : (1) a d e c r e a s e d s e n s i t i v i t y t o EB, (2) a d e c r e a s e d s e n s i t i v i t y t o P, (3) an i n c r e a s e d d e pendence on t h e s y n e r g i s t i c a c t i o n o f P w i t h EB, (4) a dependence on one o r more a d r e n a l s t e r o i d s i n a d d i t i o n t o EB and P f o r maximal r e c e p t i v i t y , (5) a n o n - s p e c i f i c d e b i l i t a t i n g e f f e c t o f a d r e n a l e c t o m y . A l t h o u g h t h e p o s s i b i l i t y t h a t a d r e n a l e c t o m y p r o d u c e s a d e c r e a s e i n s e n s i t i v i t y t o EB i n t h e g e r b i l c a n n o t be e n t i r e l y e l i m i n a t e d , t h e f a c t t h a t a t e n - f o l d i n c r e a s e i n t h e dose of EB a d m i n i s t e r e d f a i l s t o r e s t o r e r e c e p t i v i t y i n a d r e n a l e c t o m i z e d 60 g e r b i l s t o t h a t e x h i b i t e d by c o n t r o l s ( F i g u r e 5) makes i t u n l i k e l y . I n a d d i t i o n , a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g a p p r o p r i a t e a d r e n a l s t e r o i d s e x h i b i t e d n o r m a l s e n s i t i v i t y t o EB, s u g g e s t i n g t h a t a l a c k o f a p p r o p r i a t e a d r e n a l s t e r o i d s may have been, t o some e x t e n t , r e s p o n s i b l e f o r r e d u c e d r e s p o n d i n g t o EB. F u r t h e r m o r e , t h e r e s u l t s o f E x p e r i m e n t 4 i n d i c a t e d t h a t t h e g e r b i l was d e p e n d e n t on t h e s y n e r g i s t i c a c t i o n o f P w i t h EB f o r th e e l i c i t a t i o n of maximal r e c e p t i v i t y u n l e s s e x c e e d i n g l y h i g h d o s e s o f EB were a d m i n i s t e r e d . T h u s , a r e d u c t i o n i n s e n s i t i v i t y t o P i n a d r e n a l e c t o m i z e d a n i m a l s c o u l d e a s i l y r e s u l t i n l o w e r e d r e c e p t i v i t y d u r i n g t e s t i n g w i t h EB p l u s P. In s u p p o r t of t h i s , t h e r e s u l t s o f E x p e r i m e n t s 6-8 i n d i c a t e d t h a t a d r e n a l e c t o m i z e d a n i m a l s were l e s s s e n s i t i v e t h a n o v a r i e c t o m i z e d a n i m a l s t o t h e a c t i o n o f P when a d m i n i s t e r e d i n c o n j u n c t i o n w i t h EB. E x p e r i m e n t 6 i n d i c a t e d t h a t E B - p r i m e d , a d r e n a l e c t o m i z e d g e r b i l s g i v e n v a r y i n g d o s e s o f P were c o n s i s t e n t l y l e s s r e c e p t i v e t h a n o v a r i e c t o m i z e d c o n t r o l s . I n a d d i t i o n , E x p e r i m e n t s 7-8 i n d i c a t e d t h a t a d r e n a l e c t o m i z e d g e r b i l s r e c e i v i n g a d r e n a l g l u c o c o r t i c o i d s and m i n e r a l c o r t i c o i d s s t i l l e x h i b i t e d an o v e r a l l r e d u c t i o n i n r e s p o n d i n g when t e s t e d w i t h EB p l u s P a l t h o u g h n o t when t e s t e d w i t h EB a l o n e . The f i n d i n g t h a t t h e c o m b i n a t i o n of a g l u c o c o r t i c o i d and a m i n e r a l c o r t i c o i d was most e f f e c t i v e i n r e s t o r i n g c o n t r o l l e v e l s of r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s s u g g e s t s t h a t a p o r t i o n o f t h e e f f e c t o b s e r v e d i n E x p e r i m e n t s 5 and 6 may have been due t o p o o r h e a l t h . However, t h e r e s u l t s o f E x p e r i m e n t s 7 and 8 i n d i c a t e t h a t t h e r e d u c e d r e c e p t i v i t y i n a d r e n a l e c t o m i z e d a n i m a l s i s a l s o , i n p a r t , due t o a d e c r e a s e d s e n s i t i v i t y t o t h e 61 e f f e c t s of P. The g e r b i l i s t h e f i r s t known r o d e n t t o r e q u i r e a d r e n a l s t e r o i d s i n a d d i t i o n t o EB and P f o r t h e i n d u c t i o n o f maximal r e c e p t i v i t y . The f i n d i n g t h a t a d r e n a l e c t o m y does n o t f a c i l i t a t e r e c e p t i v i t y i n t h e f e m a l e g e r b i l i s s i m i l a r t o t h e r e s u l t s o b t a i n e d f o r t h e hamster ( C a r t e r , 1972) but i s i n c o n t r a s t t o t h e r e s u l t s o b t a i n e d f o r t h e r a t , where a d r e n a l e c t o m y f a c i l i t a t e s r e c e p t i v i t y (de C a t a n z a r o e t a l . , 1981; G r a y & G o r z a l k a , 1980). R e c e n t l y i t has been f o u n d t h a t t h e c h r o n i c a d m i n i s t r a t i o n o f c o r t i c o s t e r o n e ( t h e major a d r e n a l s t e r o i d o f t h e r a t ) e l i m i n a t e s t h e a d r e n a l e c t o m y f a c i l i t a t i o n e f f e c t i n EB and P t r e a t e d r a t s (de C a t a n z a r o e t a l . , 1981), s u g g e s t i n g t h a t i t m i g h t n o r m a l l y e x e r t an i n h i b i t o r y e f f e c t i n t h e o v a r i e c t o m i z e d a n i m a l . . I t i s i n t e r e s t i n g t o n o t e t h a t b o t h r o d e n t s p e c i e s w h i c h do not e x h i b i t an i n c r e a s e i n s e x u a l r e c e p t i v i t y a f t e r a d r e n a l e c t o m y ( h a m s t e r and g e r b i l ) have C o r t i s o l r a t h e r t h a n c o r t i c o s t e r o n e a s t h e i r m a j o r a d r e n a l s t e r o i d , s u g g e s t i n g t h a t knowledge of t h e major a d r e n a l s t e r o i d may a l l o w p r e d i c t i o n o f t h e e f f e c t s o f a d r e n a l e c t o m y on s e x u a l r e c e p t i v i t y i n a g i v e n s p e c i e s . The f i n d i n g t h a t h o u s i n g c o n d i t i o n s d i d not a l t e r r e c e p t i v i t y i n t h e f e m a l e g e r b i l i s i n c o n t r a s t w i t h r e s u l t s o b t a i n e d f o r t h e r a t , where i s o l a t i o n f a c i l i t a t e s s e x u a l r e s p o n d i n g ( G o r z a l k a & R a i b l e , 1981). A d r e n a l e c t o m y e l i m i n a t e s t h e f a c i l i t a t i n g e f f e c t o f i s o l a t i o n on r e c e p t i v i t y i n f e m a l e r a t s , s u g g e s t i n g t h a t t h e a d r e n a l m e d i a t e s t h e e f f e c t . I n i t i a l l y , t h e r e a p p e a r e d t o be two l i k e l y e x p l a n a t i o n s o f t h i s e f f e c t i n t h e r a t . F i r s t , s o c i a l i s o l a t i o n c o u l d have l e d t o 62 i n c r e a s e s i n a d r e n a l p r o g e s t e r o n e w h i c h t h e n a c t e d s y n e r g i s t i c a l l y w i t h e s t r o g e n t o f a c i l i t a t e r e c e p t i v i t y ( G o r z a l k a & R a i b l e , 1981). S e c o n d , s o c i a l i s o l a t i o n may have i n c r e a s e d a d r e n a l s e c r e t i o n of d e o x y c o r t i c o s t e r o n e , w h i c h f a c i l i t a t e s r e c e p t i v i t y i n f e m a l e r a t s . D e o x y c o r t i c o s t e r o n e i s n o t s e c r e t e d by t h e g e r b i l a d r e n a l . G i v e n t h e g e r b i l ' s i n c r e a s e d dependence on t h e s y n e r g i s t i c a c t i o n o f P w i t h EB, one m i g h t have e x p e c t e d t h a t , i f s o c i a l i s o l a t i o n was s t r e s s f u l t o t h e g e r b i l , a s i m i l a r e f f e c t would be o b s e r v e d . I t was n o t , d e s p i t e i n d i c a t i o n s , u s i n g t h e a d r e n a l a s c o r b i c a c i d c o n t e n t t e c h n i q u e , t h a t s o c i a l i s o l a t i o n is. s t r e s s f u l t o t h e g e r b i l (Hughes & N i c h o l a s , 1971). P e r h a p s a d r e n a l p r o g e s t e r o n e i s n o t t h e s t e r o i d i n v o l v e d , o r a t l e a s t i s n o t t h e o n l y s t e r o i d i n v o l v e d i n t h e e f f e c t o b s e r v e d i n t h e r a t . No major a d r e n a l s t e r o i d s a r e s h a r e d between t h e r a t and t h e g e r b i l . I t seems p o s s i b l e t h a t an e f f e c t o f h o u s i n g i s n o t o b s e r v e d i n t h e g e r b i l b e c a u s e t h e s t e r o i d r e s p o n s i b l e f o r t h e e f f e c t i n t h e r a t i s n o t s e c r e t e d by t h e g e r b i l a d r e n a l . M o r e o v e r , even i f i d e n t i c a l q u a n t i t i e s o f i d e n t i c a l s t e r o i d s were s e c r e t e d , r a t and g e r b i l b r a i n s c o u l d s t i l l d i f f e r i n r e l a t i v e s e n s i t i v i t i e s t o t h e r e l e v a n t s t e r o i d s . F o r example, w h i l e DHP m i m i c s p r o g e s t e r o n e i n t h e a b i l i t y t o f a c i l i t a t e EB a c t i o n i n t h e r a t ( G o r z a l k a & Whalen, 1977), i t was c o m p l e t e l y i n e f f e c t i v e i n a s i m i l a r g e r b i l p a r a d i g m ( E x p e r i m e n t 6 ) . T hus, i n t e r s p e c i f i c d i f f e r e n c e s i n e i t h e r t h e a d r e n a l s t e r o i d s s e c r e t e d , s e n s i t i v i t y t o t h e r e l e v a n t s t e r o i d s , o r b o t h , c o u l d a c c o u n t f o r t h e f a i l u r e of h o u s i n g m a n i p u l a t i o n s t o a l t e r r e c e p t i v i t y i n t h e g e r b i l . E x p e r i m e n t 6 i n d i c a t e d t h a t , i n 63 c o n t r a s t t o r e s u l t s o b t a i n e d f o r t h e r a t ( G o r z a l k a & Whalen, 1977), g u i n e a p i g (Wade & F e d e r , 1972) and some mouse s t r a i n s ( G o r z a l k a & Whalen, 1974), DHP does n o t f a c i l i t a t e r e c e p t i v i t y i n t h e E B - p r i m e d g e r b i l . T hus, 5c*.-reduction, t h e p r o c e s s by w h i c h p r o g e s t e r o n e i s n o r m a l l y c o n v e r t e d t o d i h y d r o p r o g e s t e r o n e , i n a c t i v a t e s p r o g e s t e r o n e i n t h e g e r b i l but n o t i n o t h e r s p e c i e s . E x p e r i m e n t s 5-8 i n d i c a t e d t h a t a d r e n a l e c t o m i z e d a n i m a l s r e c e i v i n g o n l y HCA were l e s s r e s p o n s i v e t o EB w h i l e t h o s e r e c e i v i n g c o m b i n a t i o n s o f a d r e n a l s t e r o i d s were o n l y l e s s r e s p o n s i v e t o t h e s y n e r g i s t i c e f f e c t s of P. E x p e r i m e n t s 7 and 8 i n d i c a t e d t h a t DOCA and DOCA + HCA may f a c i l i t a t e s e x u a l b e h a v i o u r i n t h e EB and P t r e a t e d g e r b i l . T h i s r e s u l t i s somewhat s i m i l a r t o t h a t o b t a i n e d f o r t h e r a t ( G o r z a l k a & Whalen, 1977) a l t h o u g h i t i s u n c l e a r whether o r n o t DOCA would f a c i l i t a t e r e c e p t i v i t y i n EB p l u s P t r e a t e d r a t s . However, DOCA i s s t r u c t u r a l l y s i m i l a r t o P and i s t h o u g h t t o a c t v i a P r e c e p t o r s ( G o r z a l k a & Whalen, 1977). I f s o , one would e x p e c t t h a t t h e f a c i l i t a t o r y a c t i o n of DOCA would d e c r e a s e a s t h e dose of P i n c r e a s e s s i n c e t h e two would be c o m p e t i n g f o r r e c e p t o r s i t e s . To t h e b e s t of my knowledge, t h i s s t u d y has not y e t been done. F u r t h e r i n v e s t i g a t i o n i n t o t h e a p p a r e n t l y u n i q u e r o l e o f a d r e n a l s t e r o i d s i n t h e i n d u c t i o n o f maximal r e c e p t i v i t y i n t h e f e m a l e g e r b i l w ould g r e a t l y i n c r e a s e o u r u n d e r s t a n d i n g o f t h e r o l e o f a d r e n a l s t e r o i d s i n t h e d i s p l a y of s e x u a l b e h a v i o u r . F o r many y e a r s i t was b e l i e v e d t h a t o v a r i a n s t e r o i d s were t h e s o l e r e g u l a t o r s of s e x u a l r e c e p t i v i t y i n t h e f e m a l e r o d e n t . More r e c e n t e v i d e n c e i n t h e r a t has s u g g e s t e d t h a t a d r e n a l 64 s t e r o i d s a l s o a l t e r r e c e p t i v i t y a l t h o u g h r e c e p t i v i t y i s n o t d e p e n d e n t upon t h e i r p r e s e n s e . O v a r i a n s t e r o i d s t h e n became t h e p r i m a r y r e g u l a t o r s o f s e x u a l r e c e p t i v i t y i n f e m a l e r o d e n t s and a d r e n a l s t e r o i d s became s e c o n d a r y i n f l u e n c e s . The p r e s e n t r e s u l t s s u g g e s t t h a t , i n t h e g e r b i l , o v a r i a n s t e r o i d s and a d r e n a l s t e r o i d s r e g u l a t e s e x u a l r e s p o n d i n g . T h u s , a l t h o u g h o v a r i a n s t e r o i d s a r e t h e p r i m a r y r e g u l a t o r s o f s e x u a l b e h a v i o u r , t h e r e i s r e a s o n t o doubt t h a t t h i s g e n e r a l i z a t i o n h o l d s f o r a l l r o d e n t s . R e l a t i v e l y l i t t l e work ha s been done on t h e e f f e c t s o f a d r e n a l s t e r o i d s on r e c e p t i v i t y i n r o d e n t s . Y e t r e s e a r c h on t h e e f f e c t s o f a d r e n a l s t e r o i d s on r e c e p t i v i t y does seem t o be on t h e i n c r e a s e . The a u t h o r f e e l s t h i s i s a p o s i t i v e s t e p t o w a r d s d e v e l o p i n g a more g l o b a l model o f t h e h o r m o n a l r e g u l a t i o n o f s e x u a l r e c e p t i v i t y i n r o d e n t s . 65 SECTION II Hormonal R e g u l a t i o n and S e x u a l D i f f e r e n t i a t i o n of Food I n t a k e Mechanisms and M a t i n g A c t i v i t y The r e s e a r c h o f Maass & Wade (1977) and Roy e t a l . (1977) i n d i c a t e s t h a t f e m a l e g e r b i l s may be u n l i k e o t h e r f e m a l e r o d e n t s i n t e r m s o f t h e ho r m o n a l r e g u l a t i o n o f f o o d i n t a k e and body w e i g h t . Whereas r a t s ( T a r t t e l i n & G o r s k i , 1973; Wade, 1975; Wade & Z u c k e r , 1970), mice ( W r i g h t & T u r n e r , 1973), and, t o a much l e s s e r d e g r e e , h a m s t e r s ( G e r a l l & T h i e l , 1975; M o r i n & Flemming, 1978), e x h i b i t a d e c r e a s e i n body w e i g h t and f o o d i n t a k e when EB i s a d m i n i s t e r e d , f e m a l e g e r b i l s a p p e a r t o i n c r e a s e f o o d i n t a k e and body w e i g h t i n r e s p o n c e t o EB a d m i n i s t r a t i o n (Maass & Wade, 1977). The r e s u l t s o f Maass & Wade (1977) and Roy e t a l . (1977) a r e d i f f i c u l t t o i n t e r p r e t however s i n c e t h e s e a u t h o r s d i d not i n v e s t i g a t e t h e e f f e c t o f endogenous s t e r o i d r e m o v a l (by o v a r i e c t o m y ) . F u r t h e r m o r e , t h e r e l a t i v e f u n c t i o n s of e s t r o g e n and p r o g e s t e r o n e i n r e s t o r i n g p r e s u r g i c a l l e v e l s of f o o d i n t a k e and body w e i g h t were n o t d e t e r m i n e d . The p o t e n t i a l d i f f e r e n c e i n t h e r e s p o n s e o f t h e f e m a l e g e r b i l t o EB a d m i n i s t r a t i o n i n terms o f f o o d i n t a k e and body w e i g h t i s a l s o of i n t e r e s t i n l i g h t of e v i d e n c e s u g g e s t i n g t h a t i n r o d e n t s p e c i e s where t h e male i s h e a v i e r t h a n t h e f e m a l e ( r a t s , m i c e , and g u i n e a p i g s ) , t h e g r e a t e s t a l t e r a t i o n s i n f o o d i n t a k e and body w e i g h t r e s u l t f r o m t h e a d m i n i s t r a t i o n of o v a r i a n s t e r o i d s . In t h e s p e c i e s where t h e f e m a l e i s h e a v i e r t h a n t h e male ( h a m s t e r s ) , g r e a t e r a l t e r a t i o n s a r e o b s e r v e d a f t e r t h e 66 a d m i n i s t r a t i o n of a n d r o g e n s ( K o w a l e w s k i , 1969; Wade, 1976). A p p a r e n t l y , i n t h e s m a l l e r of t h e two g e n d e r s , t h e endogenous l e v e l o f t h e more e f f e c t i v e sex hormone i s r e s p o n s i b l e f o r t h e l e s s e r w e i g h t o f t h a t g e n d e r . To be c o n s i s t e n t w i t h t h i s p a t t e r n , f o o d i n t a k e i n t h e g e r b i l s h o u l d be r e g u l a t e d by o v a r i a n s t e r o i d s as f e m a l e s a r e l i g h t e r t h a n m a l e s ( M a r s t o n & Chang, 1965) but one w o u l d e x p e c t f o o d i n t a k e and body w e i g h t t o be r e d u c e d by EB as e s t r o g e n i s assumed t o be r e l a t e d t o t h e f e m a l e ' s r e d u c e d w e i g h t . Maass & Wade's (1977) s t u d y s u g g e s t s t h a t t h e f e m a l e g e r b i l may not f i t t h e p a t t e r n e x h i b i t e d by o t h e r r o d e n t s . I f so, t h i s i n f o r m a t i o n may a s s i s t i n r e f i n i n g h o r m o n a l models of f o o d i n t a k e and body w e i g h t r e g u l a t i o n i n r o d e n t s . In a d d i t i o n t o t h e d i r e c t i o n o f t h e d i f f e r e n c e i n male and f e m a l e body w e i g h t s i n h a m s t e r s , t h e y d i f f e r from o t h e r l a b o r a t o r y r o d e n t s i n a n o t h e r r e s p e c t . U n l i k e male r a t s ( D u n l o p , G e r a l l , & H e n d r i c k s , 1972; Goldman, B a k e r , Chen, & W i e l a n d , 1972), mice (Edwards & B u r g e , 1971), and g u i n e a p i g s (Brown-Grant & Sherwood, 1971; P h e o n i x , Goy, G e r a l l , & Young, 1959), i n w h i c h b e h a v i o u r i s n a t u r a l l y d e f e m i n i z e d a t b i r t h , male h a m s t e r s a r e n o t n a t u r a l l y d e f e m i n i z e d a t b i r t h and may e x h i b i t male and f e m a l e s e x u a l b e h a v i o u r i n a d u l t h o o d ( J o h n s o n , 1975; T i e f e r & J o h n s o n , 1971, 1975; W h i t s e t t & V a n d e n b e r g h , 1975). The a d m i n i s t r a t i o n o f a n d r o g e n s t o n e o n a t a l f e m a l e r o d e n t s may a l s o i n d u c e male p a t t e r n s of s e x u a l b e h a v i o u r i n a d u l t h o o d . P r e - a n d / o r n e o n a t a l l y a d m i n i s t e r e d TP m a s c u l i n i z e s and d e f e m i n i z e s f e m a l e r a t s ( G o r s k i , 1980; Ward, 1969), mice (Edwards & Burge, 1971), and g u i n e a p i g s (Brown-Grant & 67 Sherwood, 1971; P h e o n i x e t a l . , 1959; S l o b e t a l . , 1973), and m a s c u l i n i z e s b u t o n l y p a r t i a l l y d e f e m i n i z e s f e m a l e h a m s t e r s ( J o h n s o n , 1975; T i e f e r & J o h n s o n , 1975). S t u d i e s i n t h e r a t , g u i n e a p i g , and ham s t e r i n d i c a t e t h a t t h e sex d i f f e r e n c e i n f o o d i n t a k e and body w e i g h t i n a d u l t h o o d i s r e l a t e d t o t h e p r e s e n c e or a b s e n c e o f sex s t e r o i d s a r o u n d t h e t i m e o f b i r t h ( G e n t r y & Wade, I976a,b; S l o b , Goy, & Van d e r W e r f f t e n B o s c h , 1973; Swanson, 1967; Wade & Z u c k e r , 1970). TP a d m i n i s t r a t i o n d u r i n g s e x u a l d i f f e r e n t i a t i o n p r o d u c e s m a s c u l i n e f o o d i n t a k e and body w e i g h t p a t t e r n s w h i l e n e o n a t a l c a s t r a t i o n p r o d u c e s f o o d i n t a k e and body w e i g h t p a t t e r n s s i m i l a r t o t h o s e o b s e r v e d i n t h e f e m a l e . S i n c e h a m s t e r s d i f f e r f r o m r a t s i n t h e d e g r e e o f a n d r o g e n - i n d u c e d d e f e m i n i z a t i o n and i n t h e sex s t e r o i d p r o d u c i n g t h e g r e a t e s t a l t e r a t i o n s i n f o o d i n t a k e and body w e i g h t , i t i s p o s s i b l e t h a t t h e d i f f e r e n c e s i n t h e h o r m o n a l r e g u l a t i o n of a d u l t f o o d i n t a k e and body w e i g h t s e e n between h a m s t e r s and o t h e r l a b o r a t o r y r o d e n t s a r e r e l a t e d t o t h e d e g r e e o f p e r i n a t a l a n d r o g e n i n d u c e d s e x u a l d i f f e r e n t i a t i o n o c c u r i n g i n t h e s p e c i e s . A l t h o u g h , t o t h e b e s t of my knowledge, t h e r e a r e no s t u d i e s i n d i c a t i n g t h a t d i f f e r e n t i a l e f f e c t s o f p e r i n a t a l a n d r o g e n s a r e r e s p o n s i b l e f o r between s p e c i e s d i f f e r e n c e s i n t h e h o r m o n a l r e g u l a t i o n o f b e h a v i o u r , t h e r e a r e s t u d i e s i n d i c a t i n g t h e y a r e r e s p o n s i b l e f o r w i t h i n s p e c i e s d i f f e r e n c e s . In f a c t , a g r e a t d e a l of e v i d e n c e e x i s t s i n d i c a t i n g t h a t a n d r o g e n s m o d i f y b r a i n m o r p h o l o g y ( G o r s k i , G o r d o n , S h r y n e , and Southam, 1978; R o s s , G l i c k , and M e i b a c h , 1982), n e u r a l s t r u c t u r e and d e n d r i t i c s y n a p s e s ( D d r n e r and S t a u d t , 1968, 1969; F i e l d and Raisman, 1971; G r e e n o u g h , C a r t e r , S t eerman, and De Voogd, 1977; Loy and 68 M i l n e r , 1980; N i s h i z u k a and A r a i , 1981; T o r a n - A l l e r a n d , 1976), and s t e r o i d b i n d i n g and r e t e n t i o n c a p a c i t i e s (De B o l d , 1978; G r e e n , L u t t g e , and Whalen, 1969; Maurer and Woolkey, 1971; Tuohimaa and J o h a n s s o n , 1971; Whalen & M a s s i c c i , 1975) i n v a r i o u s a r e a s o f t h e b r a i n i n r a t s , m i c e , and h a m s t e r s . S i n c e a n d r o g e n s a r e n o r m a l l y p r e s e n t i n f e t a l and n e o n a t a l m a l e s and a b s e n t i n f e m a l e s , t h i s r e s u l t s i n a s e x u a l d i m o r p h i s m of t h e b r a i n and p r e s u m a b l y i s r e s p o n s i b l e f o r s e x u a l d i m o r p h i s m s i n h o r m o n a l l y m e d i a t e d b e h a v i o u r s s u c h as f o o d i n t a k e . I n v e s t i g a t i o n i n t o t h e d e g r e e of d e f e m i n i z a t i o n a t b i r t h and t h e l a t e r h o r m o n a l c o n t r o l o f f o o d i n t a k e and body w e i g h t i n t h e g e r b i l s h o u l d p r o v i d e some i n t e r e s t i n g i n f o r m a t i o n . T h i s i n f o r m a t i o n c o m b i n e d w i t h t h a t o b t a i n e d i n o t h e r s p e c i e s w i l l i m prove t h e p r e s e n t u n d e r s t a n d i n g o f t h e i n t e r r e l a t i o n of e a r l y h o r m o n a l e n v i r o n m e n t and a d u l t f o o d i n t a k e and body w e i g h t p a t t e r n s . I f o v a r i a n s t e r o i d s do a p p e a r t o be more e f f e c t i v e t h a n a n d r o g e n s i n a l t e r i n g f o o d i n t a k e and body w e i g h t i n t h e g e r b i l , and i f t h e a d m i n i s t r a t i o n o f a n d r o g e n a r o u n d t h e t i m e of b i r t h does d e f e m i n i z e t h e g e r b i l , i t w o u l d f u r t h e r s u p p o r t t h e p r e s e n t h y p o t h e s i s t h a t e a r l y h o r m o n a l e n v i r o n m e n t may d e t e r m i n e w h i c h sex s t e r o i d w i l l l a t e r r e g u l a t e f o o d i n t a k e and body w e i g h t i n r o d e n t s . A f a i l u r e t o o b s e r v e d e f e m i n i z a t i o n a f t e r a n d r o g e n t r e a t m e n t i n t h e f e m a l e g e r b i l w o u l d s u g g e s t t h a t t h e e x t e n t o f s e x u a l d i f f e r e n t i a t i o n a t b i r t h may not be c l o s e l y r e l a t e d t o w h i c h sex s t e r o i d w i l l m e d i a t e a d u l t f o o d i n t a k e and body w e i g h t . To t h e b e s t o f my knowledge, t h i s i s t h e f i r s t t i m e t h a t t h e p o s s i b l e r e l a t i o n s h i p between e a r l y h o r m o n a l e n v i r o n m e n t and i n t e r s p e c i f i c d i f f e r e n c e s i n t h e h o r m o n a l 69 r e g u l a t i o n of a d u l t f o o d i n t a k e and body w e i g h t has been i n v e s t i g a t e d . Thus, t h e p u r p o s e o f t h e p r e s e n t s e r i e s o f e x p e r i m e n t s i s t o (1) d e t e r m i n e t h e e f f e c t s o f o v a r i a n s t e r o i d s on a d u l t f o o d i n t a k e and body w e i g h t p a t t e r n s i n male and f e m a l e g e r b i l s and (2) t e s t t h e h y p o t h e s i s t h a t t h e e x t e n t o f a n d r o g e n i n d u c e d d e f e m i n i z a t i o n d u r i n g t h e p e r i o d o f s e x u a l d i f f e r e n t i a t i o n d e t e r m i n e s w h i c h sex s t e r o i d has t h e g r e a t e s t i n f l u e n c e on f o o d i n t a k e and body w e i g h t r e g u l a t i o n i n a d u l t h o o d . I l a - Food I n t a k e , Body W e i g h t , and L o r d o s i s O v a r i a n s t e r o i d s have been r e p o r t e d t o i n f l u e n c e f o o d i n t a k e and body w e i g h t i n a v a r i e t y o f s p e c i e s ( s e e Wade, 1976, f o r a r e v i e w ) . F o r example, o v a r i e c t o m y r e s u l t s i n a w e i g h t g a i n w h i l e e s t r o g e n t r e a t m e n t r e d u c e s body w e i g h t i n f e m a l e r a t s ( T a r t t e l i n & G o r s k i , 1973; Wade, 1975; Wade & Z u c k e r , 1970), mice ( W r i g h t & T u r n e r , 1973), and g u i n e a p i g s ( S l o b e t a l . , 1973). In male r a t s , c a s t r a t i o n l e a d s t o s l i g h t r e d u c t i o n s i n body w e i g h t and f o o d i n t a k e ( G e n t r y & Wade, 1976b; K a k o l e w s k i , Cox, & V a l e n s t e i n , 1968; Wade, 1976). A d d i t i o n a l s t u d i e s have i n d i c a t e d t h a t P not o n l y a t t e n u a t e s t h e e f f e c t s o f EB oh f o o d i n t a k e and body w e i g h t i n o v a r i e c t o m i z e d r a t s ( R o b e r t s , Kenny, & Mook, 1972; Ross & Z u c k e r , 1974; Wade, 1975) but a l s o a t t e n u a t e s t h e e f f e c t s o f h i g h d o s e s o f TP on f o o d i n t a k e and body w e i g h t i n c a s t r a t e d male r a t s ( G e n t r y & Wade, 1976b). F o l l o w i n g a r e v i e w of t h e l i t e r a t u r e , Wade (1976) s u g g e s t e d t h a t , b e c a u s e o v a r i a n hormones a r e c o n s i d e r a b l y more e f f e c t i v e t h a n a n d r o g e n s i n a l t e r i n g f o o d i n t a k e and body w e i g h t i n t h e r a t , t h e y a r e t h e 70 p r i m a r y h o r m o n a l r e g u l a t o r s of f o o d i n t a k e and body w e i g h t i n t h a t s p e c i e s . O v a r i e c t o m y and EB t r e a t m e n t have a l s o been f o u n d t o l e a d t o w e i g h t g a i n and l o s s , r e s p e c t i v e l y , i n t h e f e m a l e h a m s t e r ( G e r a l l & T h i e l , 1975; M o r i n & F l e m i n g , 1978). The e f f e c t s a r e l e s s p r o n o u n c e d t h a n t h o s e o b s e r v e d i n t h e r a t and may, a c c o r d i n g t o M o r i n & F l e m i n g ( 1 9 7 8 ) , e x p l a i n why some r e s e a r c h e r s ( e . g . , K o w a l e s k i e t a l . , 1969; Swanson, 1967; Z u c k e r , Wade, & Z e i g l e r , 1972) have f a i l e d t o o b s e r v e s i g n i f i c a n t e f f e c t s . U n l i k e male r a t s , male h a m s t e r s e x h i b i t i n c r e a s e s i n f o o d i n t a k e and body w e i g h t a f t e r c a s t r a t i o n (Swanson, 1967; K o w a l e s k i e t a l . , 1969; Z u c k e r , Wade, & Z i e g l e r , 1972). F u r t h e r m o r e , EB a p p e a r s t o have no e f f e c t on body w e i g h t o r f o o d i n t a k e i n t h e c a s t r a t e d male h a m s t e r ( K o w a l e s k i , 1969; Z u c k e r e t a l . , 1972) whereas TP t r e a t m e n t r e d u c e s b o t h f o o d i n t a k e and body w e i g h t i n t h e male h a m s t e r ( Z u c k e r e t a l . , 1972). T h i s l e d Wade (1976) t o s u g g e s t t h a t , i n t h e h a m s t e r , a n d r o g e n s a r e t h e i m p o r t a n t a c t i v a t i n g hormones f o r t h e r e g u l a t i o n o f f o o d i n t a k e and body w e i g h t i n t h a t s p e c i e s . Maass & Wade (1977) examined f o o d i n t a k e and body w e i g h t c h a n g e s i n r e s p o n s e t o c a s t r a t i o n and a n d r o g e n t r e a t m e n t i n male M o n g o l i a n g e r b i l s and i n r e s p o n s e t o t h e a d m i n i s t r a t i o n of o v a r i a n hormones i n o v a r i e c t o m i z e d f e m a l e g e r b i l s . They f o u n d t h a t c a s t r a t i o n l e d t o i n c r e a s e s i n body w e i g h t w i t h o u t a l t e r i n g f o o d i n t a k e . T h i s e f f e c t i s somewhat s i m i l a r t o t h a t o b s e r v e d i n t h e male h a m s t e r , w h i c h a l s o e x h i b i t s a w e i g h t i n c r e a s e a f t e r c a s t r a t i o n (Swanson, 1967; Z u c k e r e t a l . , 1972). U n l i k e t h e male h a m s t e r , t h e male g e r b i l e x h i b i t s no change i n f o o d i n t a k e 71 o r body w e i g h t i n r e s p o n s e t o TP a d m i n i s t r a t i o n (Maass & Wade, 1977). Maass & Wade (1977) a l s o f o u n d t h a t o v a r i e c t o m i z e d , EB-t r e a t e d g e r b i l s g a i n e d s i g n i f i c a n t l y more w e i g h t and a t e more t h a n o v a r i e c t o m i z e d g e r b i l s g i v e n v e h i c l e i n j e c t i o n s . Even more i n t r i g u i n g was t h e f i n d i n g t h a t P, g i v e n i n c o n j u n c t i o n w i t h EB, r e s u l t e d i n a f u r t h e r i n c r e a s e i n f o o d i n t a k e , t o l e v e l s s i g n i f i c a n t l y above t h o s e e x h i b i t e d by a n i m a l s g i v e n EB a l o n e (Maass & Wade, 1977). T h u s , u n l i k e o t h e r f e m a l e r o d e n t s w h i c h d e m o n s t r a t e d e c r e a s e d w e i g h t and i n t a k e i n r e s p o n s e t o EB and an a t t e n u a t i o n o f t h i s e f f e c t when a l s o g i v e n P, f e m a l e g e r b i l s a p p e a r t o e x h i b i t an i n c r e a s e i n w e i g h t and i n t a k e i n r e s p o n s e t o EB, w i t h P e l i c i t i n g a f u r t h e r i n c r e a s e i n f o o d i n t a k e . The r e s u l t s o f Maass & Wade (1977) a r e o f c o n s i d e r a b l e i n t e r e s t a s t h e y s u g g e s t t h a t f e m a l e g e r b i l s a r e u n l i k e o t h e r f e m a l e r o d e n t s s t u d i e d t o d a t e i n t h e i r h o r m o n a l r e g u l a t i o n o f f o o d i n t a k e and body w e i g h t . However, t h e p h y s i o l o g i c a l s i g n i f i c a n c e o f t h e s e r e s u l t s r e m a i n s t o be d e t e r m i n e d . E x p e r i m e n t 9 w i l l examine t h e e f f e c t s o f o v a r i e c t o m y , EB d o s e , and t h e e f f e c t s o f P, a l o n e and i n c o n j u n c t i o n w i t h EB, on f o o d i n t a k e and body w e i g h t . M o r e o v e r , l o r d o s i s b e h a v i o u r w i l l a l s o be examined i n o r d e r t h a t t h e r e l a t i v e e f f e c t i v e n e s s o f o v a r i a n hormones i n p r o d u c i n g a l t e r a t i o n s i n f o o d i n t a k e and s e x u a l r e c e p t i v i t y c a n be compared. GENERAL METHODS Male and f e m a l e M o n g o l i a n g e r b i l s were o b t a i n e d f r o m Tumblebrook Farms a t 90 d a y s of age and h o u s e d i n d i v i d u a l l y i n s t a n d a r d l a b o r a t o r y s i n g l e c a g e s w i t h w i r e b o t t o m s . A 12:12 h r 72 l i g h t - d a r k c y c l e was m a i n t a i n e d t h r o u g h o u t t h e e x p e r i m e n t w i t h f o o d and w a t e r a v a i l a b l e ad l i b i t u m . To p r e v e n t f o o d p e l l e t s f r o m d r o p p i n g t h r o u g h t h e c a g e b o t t o m s b e f o r e t h e y were.consumed, o n l y p e l l e t s w e i g h i n g more t h a n 4.5 g were u s e d . Food was p l a c e d i n s i d e t h e c a g e s t o i n s u r e t h a t f o o d w h i c h d i d d r o p t h r o u g h t h e c a g e would f a l l o n t o t h e p a p e r below e a c h c a g e where i t c o u l d be e a s i l y c o l l e c t e d . F o o d i n t a k e was d e t e r m i n e d e v e r y 24 h r by s u b t r a c t i n g t h e w e i g h t of t h e f o o d r e m a i n i n g i n s i d e and below e a c h c a g e from t h e w e i g h t of t h e f o o d s u p p l i e d 24 h r b e f o r e . F o o d was weighed t o t h e n e a r e s t 0.01 g on an a n a l y t i c a l b a l a n c e ( M e t t l e r , model A C 8 8 ) . I m m e d i a t e l y a f t e r c o n s u m p t i o n d a t a were c o l l e c t e d , a n i m a l s were weighed t o t h e n e a r e s t 0.5 g on a t r i p l e beam b a l a n c e (Ohaus, model 700) and, i f a p p r o p r i a t e , r e c e i v e d s u b c u t a n e o u s i n j e c t i o n s . T h r e e d a y s a f t e r t h e a n i m a l s were i n t r o d u c e d t o t h e c o l o n y , d a i l y measurements o f f o o d i n t a k e and body w e i g h t commenced and c o n t i n u e d t h r o u g h o u t t h e e x p e r i m e n t . The f i r s t f o u r d a y s o f measurements p r o v i d e d b a s e l i n e d a t a t h a t were u s e d t o s u b d i v i d e t h e a n i m a l s i n t o f o u r matched g r o u p s . Over t h e n e x t two d a y s , a n i m a l s were e i t h e r g o n a d e c t o m i z e d w h i l e under a n a e s t h e s i a g r a d e e t h e r ( e x p e r i m e n t a l g r o u p s ) o r l e f t i n t a c t ( c o n t r o l g r o u p s ) . D u r i n g t h e p h a s e s o f hormone a d m i n i s t r a t i o n , i n t a c t c o n t r o l a n i m a l s ( I C ) r e c e i v e d d a i l y i n j e c t i o n s o f t h e v e h i c l e , 0.01 c c p e a n u t o i l . The d o s e s o f EB e m p l o y e d were 1 ^ ug ( g r o u p E 1 ) , 10 jug ( g r o u p E 1 0 ) , o r 100 jug ( g r o u p E100) a d m i n i s t e r e d d a i l y . B e c a u s e E x p e r i m e n t 2 i n d i c a t e d t h a t 100 jug P i s t h e m i n i m a l e f f e c t i v e d o s e f o r t h e e l i c i t a t i o n o f h i g h l e v e l s o f r e c e p t i v i t y 73 i n E B - p r i m e d g e r b i l s , t h i s d o se was u s e d t o t e s t t h e p o t e n t i a l of P a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n E B - p r i m e d g e r b i l s . T e s t s of l o r d o s i s o c c u r r e d on Days 3-12 o f EB t r e a t m e n t ( f o r d e t a i l s , see e x p e r i m e n t 4 ) . D u r i n g t h e l a t t e r p o r t i o n o f p h a s e 2 (EB) and t h e s t a r t of p h a s e 3 (EB+P), some a n i m a l s i n g r o u p s E10 and E100 began l o s i n g w e i g h t and e v e n t u a l l y d i e d . A u t o p s y s u g g e s t e d t h a t d e a t h was p r o b a b l y due t o i n t e r n a l hemmorrhage, p r e s u m a b l y r e l a t e d t o t h e c h r o n i c EB t r e a t m e n t . A f t e r two a n i m a l s i n a g i v e n g r o u p had d i e d , t h e i n j e c t i o n s were t e r m i n a t e d i n t h a t g r o u p . E10 m a l e s and E10 and E100 f e m a l e s were t e r m i n a t e d from t h e s t u d y d u r i n g t h e E B + P ph a s e and E100 males were t e r m i n a t e d d u r i n g t h e EB p hase and were e l i m i n a t e d from t h e a n a l y s i s . A 4 ( o r 3 f o r m a l e s ) x2x5 ( g r o u p s , t r e a t m e n t p h a s e , d a t a p o i n t s ) a n a l y s i s o f v a r i a n c e f o r r e p e a t e d m e a s u r e s and n e s t e d f a c t o r s was p e r f o r m e d on t h e d a t a p r o v i d e d by f e m a l e s and m a l e s i n g r o u p s IC, E l , and E10, and, f o r f e m a l e s , g r o u p E100 d u r i n g t h e f i r s t two p h a s e s o f e a c h e x p e r i m e n t (gonadectomy and EB t r e a t m e n t ) . A 2x5x5 a n a l y s i s of v a r i a n c e f o r r e p e a t e d m e asures and n e s t e d f a c t o r s was p e r f o r m e d on d a t a g e n e r a t e d by g r o u p s IC and E1 t h r o u g h o u t e a c h e x p e r i m e n t . A l l s u b s i d i a r y a n a l y s e s u s e d t h e Newman-Keuls's p r o c e d u r e w i t h o- s e t a t 0.05. Due t o t h e n e s t e d f a c t o r s and t h e q u a n t i t y o f i n f o r m a t i o n , t h e i n i t i a l 3 weeks a f t e r s u r g e r y were e l i m i n a t e d . The r e m a i n i n g d a t a were c o n d e n s e d and t h e number o f d a t a p o i n t s p e r t r e a t m e n t p h a s e were e q u a l i z e d . T h u s , e a c h t r e a t m e n t c o n s i s t e d of f i v e p o i n t s w i t h e a c h p o i n t r e p r e s e n t i n g t h e g r o u p s mean of t h e a v e r a g e s of t h e i n d i v i d u a l a n i m a l s o v e r 3 - 6 day p e r i o d s . 74 EXPERIMENT 9 Work i n our l a b o r a t o r y on t h e s e x u a l b e h a v i o u r o f f e m a l e g e r b i l s h as i n d i c a t e d t h a t o v a r i e c t o m i z e d g e r b i l s may be l e s s s e n s i t i v e t o EB a n d / o r more d e p e n d e n t on t h e s y n e r g i s t i c a c t i o n o f P w i t h EB t h a n o v a r i e c t o m i z e d r a t s ( S e c t i o n I ) . I n r a t s , d o s e s o f EB t h a t a l t e r f o o d i n t a k e and body w e i g h t a l s o i n d u c e s e x u a l r e c e p t i v i t y ( D a v i d s o n e t a l . , 1968; Wade, 1976). T h i s s u g g e s t s t h a t i n t h e r a t , t h e s y s t e m r e g u l a t i n g f o o d i n t a k e and body w e i g h t i s ab o u t as s e n s i t i v e t o EB as t h e s y s t e m r e g u l a t i n g r e c e p t i v i t y . The d e c r e a s e d s e n s i t i v i t y t o EB i n t h e f e m a l e g e r b i l may o r may not be r e s t r i c t e d t o s e x u a l b e h a v i o u r . Thus, when d e t e r m i n i n g t h e EB d o s e s t o be u s e d i n t h e p r e s e n t e x p e r i m e n t , an a t t e m p t was made t o a p p r o x i m a t e d o s e s w h i c h would r e p r e s e n t low, mo d e r a t e , and h i g h l e v e l s of EB. In t h i s manner, we a t t e m p t e d t o o b s e r v e any d i f f e r e n t i a l e f f e c t s o f EB dose on s e x u a l b e h a v i o u r , f o o d i n t a k e and body w e i g h t . Methods Once body w e i g h t s had s t a b i l i z e d a f t e r s u r g e r y (Phase 1 ) , EB t r e a t m e n t s (Phase 2) were i n i t i a t e d and c o n t i n u e d u n t i l t h e a v e r a g e body w e i g h t o f E1 a n i m a l s was s i m i l a r t o t h a t o f t h e IC a n i m a l s . T h i s a l l o w e d a more a c c u r a t e c o m p a r i s o n of t h e e f f e c t s o f t h e n e x t t r e a t m e n t p h a s e (EB + P) w i t h c o n t r o l a n i m a l s . D u r i n g t h e EB +P p h a s e , a n i m a l s i n g r o u p s E1, E10, and E100 r e c e i v e d 100 jig P d a i l y i n c o n j u n c t i o n w i t h t h e i r r e s p e c t i v e EB d o s e s w h i l e IC a n i m a l s c o n t i n u e d t o r e c e i v e i n j e c t i o n s ' o f t h e v e h i c l e . When body w e i g h t had a g a i n s t a b i l i z e d , EB was wi t h d r a w n (Phase 4) and E1 a n i m a l s c o n t i n u e d t o r e c e i v e 100 jjq P d a i l y ( g r o u p s E10 and E100 had been t e r m i n a t e d by t h i s p h a s e ) . 75 F i n a l l y , P was w i t h d r a w n (Phase 5) and t h e e f f e c t s o f no hormone t r e a t m e n t o b s e r v e d . A l l E l , E10, and E100 a n i m a l s d y i n g w i t h i n one week o f t h e t e r m i n a t i o n o f any t r e a t m e n t phase were e l i m i n a t e d f r o m t h e a n a l y s i s . The r e s u l t a n t numbers of s u b j e c t s f o r f o o d i n t a k e and body w e i g h t d a t a were 8 f o r g r o u p s IC and E10, and 7 f o r g r o u p s E1 and E100. As no a n i m a l s had d i e d w i t h i n a week of t h e l a s t day o f s e x u a l t e s t i n g , t h e number of a n i m a l s f o r g r o u p s E1, E10, and E100 u s e d i n t h e a n a l y s i s was 9. IC a n i m a l s d i d n o t r e c e i v e EB t r e a t m e n t and were t h u s n o t t e s t e d f o r s e x u a l r e c e p t i v i t y . R e s u l t s and D i s c u s s i o n T h r e e day a v e r a g e s f o r body w e i g h t and f o o d i n t a k e a r e p r e s e n t e d f o r a l l g r o u p s i n F i g u r e 9. An e x a m i n a t i o n of t h e d a t a s u g g e s t e d t h a t E1, E10, and E100 a n i m a l s e x h i b i t e d a d e c r e a s e i n w e i g h t and i n t a k e a f t e r o v a r i e c t o m y . w h i l e EB t r e a t m e n t i n c r e a s e d w e i g h t and i n t a k e . A n a l y s i s of t h e body w e i g h t d a t a i n d i c a t e d a s i g n i f i c a n t g r o u p by p o i n t i n t e r a c t i o n , F ( 2 4 , 2 0 8 ) = 4.01, g < 0.0001. F u r t h e r a n a l y s i s of t h i s i n t e r a c t i o n r e v e a l e d t h a t IC a n i m a l s w eighed s i g n i f i c a n t l y more t h a n E1 a n i m a l s on t h e l a s t t h r e e p o i n t s (14 d a y s ) of Phase 1 ( o v a r i e c t o m y ) and t h e f i r s t two p o i n t s o f Phase 2 (EB t r e a t m e n t ) , g < 0.05. By t h e l a s t two p o i n t s o f Phase 2, E1, E10, and E100 a n i m a l s had body w e i g h t s s i m i l a r t o t h o s e of IC a n i m a l s but E100 a n i m a l s w e i g h e d s i g n i f i c a n t l y more t h a n E1 and E10 a n i m a l s , g < 0.05. Thus, o v a r i e c t o m y d e c r e a s e d body w e i g h t w h i l e EB r e s t o r e d i t t o c o n t r o l l e v e l s i n a manner t h a t v a r i e d s l i g h t l y w i t h d o s e . A s i g n i f i c a n t g r o u p by Phase i n t e r a c t i o n was f o u n d f o r f o o d i n t a k e d a t a , F ( 3 , 2 6 ) = 6.11, g = 0.003, w i t h 76 F i g u r e 9. E f f e c t s o f o v a r i e c t o m y and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n f e m a l e g e r b i l s . F o o d i n t a k e and body w e i g h t were measured d a i l y and t h r e e day a v e r a g e s were r e c o r d e d . D a t a f o r i n t a c t c o n t r o l s ( I C ) and a n i m a l s r e c e i v i n g 1 j j g e s t r a d i o l b e n z o a t e (E1) d u r i n g e s t r a d i o l b e n z o a t e (EB) p h a s e s a r e p r e s e n t e d f o r a l l p h a s e s o f t h e e x p e r i m e n t . F o r p r o g e s t e r o n e (P) p h a s e s , a dose o f 100 j j g was u s e d . The phase s e q u e n c e i s from t o p t o b o t t o m i n t h e f i g u r e . F o o d i n t a k e and body w e i g h t means f o r g r o u p s E10 (10 j j g EB) and E100 (100 ^ pg EB) a r e p r e s e n t e d f o r t h e f i r s t two p h a s e s o f t h e e x p e r i m e n t . T h e s e g r o u p s were l a t e r d i s c o n t i n u e d when d e t r i m e n t a l e f f e c t s o f h i g h d o s e s o f c h r o n i c EB were o b s e r v e d . Body Weight (grams) LL 78 f u r t h e r a n a l y s i s i n d i c a t i n g t h a t E100 a n i m a l s a t e more t h a n a l l o t h e r g r o u p s d u r i n g t h e EB p h a s e , p_ < 0.05, w h i l e E1 and E10 a n i m a l s were f o u n d t o consume a b o u t as much as c o n t r o l a n i m a l s . F i n a l l y , t h e r e was a s i g n i f i c a n t e f f e c t of Phase f o r body w e i g h t , F ( 1 , 2 6 ) = 170.79, p_ < 0.0001, and f o o d i n t a k e F (1,26) = 42.43, p < 0.0001. The r a t i o of means f o r E1:IC a n i m a l s , e x p r e s s e d as a p e r c e n t a g e , i s p r e s e n t e d i n F i g u r e 10. D a t a o b t a i n e d from g r o u p s IC and E1 t h r o u g h o u t t h e e x p e r i m e n t s u g g e s t t h a t t r e a t m e n t i n Phase 3 (EB + P) i n c r e a s e d f o o d i n t a k e w i t h o u t a l t e r i n g body w e i g h t . W i t h d r a w a l o f EB (Phase 4) d e c r e a s e d body w e i g h t w i t h o u t a l t e r i n g f o o d i n t a k e and w i t h d r a w a l of P (Phase 5) a p p e a r e d t o c a u s e no f u r t h e r w e i g h t l o s s and an e v e n t u a l r e t u r n of n o r m a l f o o d c o n s u m p t i o n . A n a l y s i s o f t h e i n t a k e and w e i g h t d a t a o f g r o u p s IC and E1 f o r a l l p h a s e s o f t h e e x p e r i m e n t i n d i c a t e d a s i g n i f i c a n t g r o u p by Phase i n t e r a c t i o n f o r body w e i g h t , F ( 4 , 5 2 ) = 6.17, p = 0.0004, and f o o d i n t a k e , F (4,52) = 2.96, p = 0.03 ( T a b l e 1 ) . F u r t h e r a n a l y s i s o f t h e s e i n t e r a c t i o n s r e v e a l e d t h a t d u r i n g Phase 1 ( o v a r i e c t o m y ) , IC a n i m a l s w e i g h e d more and consumed more f o o d t h a n E1 a n i m a l s , p < 0.05. However, d u r i n g Phase 2 ( E B ) , t h e r e were no s i g n i f i c a n t d i f f e r e n c e s between t h e two g r o u p s w i t h r e s p e c t t o f o o d i n t a k e and body w e i g h t , s u g g e s t i n g t h a t 1 ug EB was s u f f i c i e n t t o r e s t o r e n o r m a l w e i g h t and i n t a k e i n o v a r i e c t o m i z e d g e r b i l s . IC and E1 a n i m a l s were a l s o f o u n d t o be of s i m i l a r w e i g h t d u r i n g Phase 3 (EB + P) a l t h o u g h E1 a n i m a l s a t e s i g n i f i c a n t l y more f o o d t h a n IC a n i m a l s d u r i n g t h a t p h a s e , p < 0.05. The f i n d i n g t h a t E1 a n i m a l s a l s o a t e more d u r i n g 79 F i g u r e 1 0 . E f f e c t s o f o v a r i e c t o m y and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n f e m a l e g e r b i l s r e l a t i v e t o l e v e l s e x h i b i t e d by i n t a c t c o n t r o l a n i m a l s . D a i l y measures of f o o d i n t a k e and body w e i g h t were a v e r a g e d t o c r e a t e f i v e d a t a p o i n t s p e r t r e a t m e n t p h a s e , p r e s e n t e d on t h e a b s c i s s a . The o r d i n a t e i s t h e r a t i o o f e x p e r i m e n t a l a n i m a l s c o r e s t o i n t a c t c o n t r o l a n i m a l s c o r e s , e x p r e s s e d as a p e r c e n t a g e . E s t r a d i o l b e n z o a t e (EB) and p r o g e s t e r o n e (P) d o s e s were 1 and 100 ;jg, r e s p e c t i v e l y . 120 110-1 c§ 100 o 90 80 Ovex Ml EB I = Weight • = Intake 81 T a b l e 1. Mean f o o d i n t a k e and body w e i g h t i n f e m a l e g e r b i l s a s a f u n c t i o n o f o v a r i e c t o m y and o v a r i a n s t e r o i d t r e a t m e n t . PHASE OVX EB EB+P P NH BODY WEIGHT X ±SE 68.87 74.29 77.89 77.47 75.89 .66 .82 .81 .84 .83 _ E1 X ±SE 65.88 0.93 71.91 1.38 75.51 1.23 69.89 1.18 67.75 0.70 FOOD INTAKE IC X ±SE 8.67 0.23 8.60 0.29 9.23 0.22 7.88 0.17 7.92 0.19 J E1 X ±SE 7.66 0.14 8.69 0.14 8.90 0.28 8.31 0.25 8.29 0.25 IC = i n t a c t c o n t r o l a n i m a l s w h i c h r e c e i v e d no hormone t r e a t m e n t s . E1 = a n i m a l s r e c e i v e d 1 _pg e s t r a d i o l b e n z o a t e (EB) d u r i n g EB p h a s e s and 100 ^ ug p r o g e s t e r o n e (P) d u r i n g P p h a s e s . NH = no hormone t r e a t m e n t . 82 E B + P t r e a t m e n t t h a n t h e y had when g i v e n EB a l o n e , £ < 0.05, s u g g e s t s t h a t P a c t s i n a s y n e r g i s t i c or a d d i t i v e manner w i t h EB i n r e g u l a t i n g f o o d i n t a k e but not body w e i g h t . The a n a l y s i s of t h e g r o u p by Phase i n t e r a c t i o n a l s o r e v e a l e d t h a t E1 a n i m a l s w e i g h e d l e s s t h a n IC a n i m a l s f o r P h a s e s 4 and 5 (P and no hormone t r e a t m e n t , p < 0.05) a l t h o u g h t h e E1 a n i m a l s c o n t i n u e d t o e a t more t h a n t h e IC a n i m a l s d u r i n g t h o s e p h a s e s , p < 0.05. The f i n d i n g t h a t t h e body w e i g h t of E1 a n i m a l s f o r P h a s e s 4 and 5 d i d n o t d i f f e r s u g g e s t s t h a t t h e w e i g h t d e c r e a s e o b s e r v e d i n Phase 4 was, i n p a r t , due t o t h e w i t h d r a w a l o f EB t r e a t m e n t r a t h e r t h a n an e f f e c t o f P. However, i t i s a l s o p o s s i b l e t h a t P was e x e r t i n g a m e t a b o l i c e f f e c t w h i c h r e q u i r e d e l e v a t e d f o o d i n t a k e t o c o u n t e r a c t an i n c r e a s e i n m e t a b o l i c r a t e . The p r e s e n t e x p e r i m e n t does n o t a l l o w t h e d i f f e r e n t i a t i o n of t h e s e p o s s i b i l i t i e s . O t h e r e f f e c t s f o u n d t o be s i g n i f i c a n t f o r body w e i g h t d a t a were Phase, F ( 4 , 5 2 ) = 33.73, p < 0.0001, p o i n t s , F (20,260) = 15.91, p < 0.0001, and g r o u p by p o i n t s , F ( 2 0 , 260) = 4.77, p < 0.0001. F o r f o o d i n t a k e , s i g n i f i c a n t e f f e c t s were f o u n d f o r Phase, F ( 4 , 5 2 ) = 10.56, p < 0.0001, and p o i n t s , F (20,260) = 1.83, p = 0.02. O v e r a l l , t h e s e r e s u l t s s u g g e s t t h a t o v a r i e c t o m y d e c r e a s e s body w e i g h t and f o o d i n t a k e whereas e s t r o g e n s e r v e s t o i n c r e a s e body w e i g h t and f o o d i n t a k e , e f f e c t s o p p o s i t e t o t h o s e f o u n d i n o t h e r l a b o r a t o r y r o d e n t s . F u r t h e r m o r e , r a t h e r t h a n a t t e n u a t i n g t h e e f f e c t s of EB on f o o d i n t a k e , P a p p e a r s t o a c t i n an a d d i t i v e a n d / o r s y n e r g i s t i c manner w i t h EB t o i n c r e a s e f o o d i n t a k e w i t h o u t a l t e r i n g body w e i g h t . B e c a u s e P may e x e r t 83 e f f e c t s t h a t a r e i n d e p e n d e n t of i t s a c t i o n w i t h EB, one c a n n o t d e t e r m i n e whether i t s e f f e c t w i t h EB i s a d d i t i v e or s y n e r g i s t i c . Mean l o r d o s i s q u o t i e n t s f o r t h e c h r o n i c e s t r o g e n t r e a t m e n t were p r e s e n t e d i n F i g u r e 4. The a n a l y s i s p e r f o r m e d ( s e e E x p e r i m e n t 4 f o r d e t a i l s ) i n d i c a t e d t h a t n e i t h e r t h e 1 ^ ug nor t h e 10 _pg dose l e d t o l e v e l s of r e c e p t i v i t y o b s e r v e d i n a n i m a l s g i v e n 100 jag EB. The 1 jjg and 10 j j g EB d o s e s d i d not d i f f e r s i g n i f i c a n t l y from e a c h o t h e r . F u r t h e r m o r e , o n l y t h e 100 ^ jg EB do s e was s u f f i c i e n t t o i n d u c e h i g h l e v e l s of r e c e p t i v i t y . T h i s c o n t r a s t s w i t h t h e a b i l i t y of 1 and 10 j j g EB t o r e s t o r e f o o d i n t a k e and body w e i g h t i n o v a r i e c t o m i z e d a n i m a l s t o l e v e l s e x h i b i t e d by i n t a c t c o n t r o l s . T h u s , t h e d o s e o f EB w h i c h a d e q u a t e l y r e s t o r e s f o o d i n t a k e and body w e i g h t a f t e r o v a r i e c t o m y (1 j j g ) does n o t f u l l y r e s t o r e s e x u a l r e c e p t i v i t y . T h i s s u g g e s t s t h a t t h e s y s t e m r e g u l a t i n g s e x u a l b e h a v i o u r i n t h e g e r b i l i s l e s s s e n s i t i v e t o EB t h a n t h e s y s t e m r e g u l a t i n g f e e d i n g b e h a v i o u r . EXPERIMENT 10 Be c a u s e o v a r i a n hormones d i d e x e r t an e f f e c t on f o o d i n t a k e and body w e i g h t i n t h e f e m a l e g e r b i l ( E x p e r i m e n t 9 ) , i t i s p o s s i b l e t h a t t h e y may a l s o e x e r t e f f e c t s on consummatory b e h a v i o u r and body w e i g h t i n t h e male g e r b i l . E v i d e n c e i n d i c a t e s t h a t , w h i l e c a s t r a t i o n i n c r e a s e s body w e i g h t i n t h e male g e r b i l , a n d r o g e n r e p l a c e m e n t has l i t t l e i n f l u e n c e on f o o d i n t a k e and body w e i g h t i n male c a s t r a t e s (Maass & Wade, 1977). However, i t may be t h a t b o t h male and f e m a l e g e r b i l s a r e more s e n s i t i v e t o o v a r i a n s t e r o i d s w i t h r e s p e c t t o f o o d i n t a k e and 84 body w e i g h t r e g u l a t i o n , a s a p p e a r s t o be t h e c a s e i n t h e r a t ( R o b e r t s e t a l . , 1972; Ross & Z u c k e r , 1974; Wade, 1975, 1976). T h u s , t h e p r e s e n t e x p e r i m e n t was c a r r i e d o u t i n o r d e r t o i n v e s t i g a t e t h e p o s s i b l e e f f e c t s of o v a r i a n s t e r o i d s on t h e s e r e s p o n s e s i n t h e male g e r b i l . In a d d i t i o n , t h e e f f e c t s o f c a s t r a t i o n were examined i n an a t t e m p t t o r e p l i c a t e t h e f i n d i n g o f Maass & Wade (1977) t h a t c a s t r a t i o n i n c r e a s e s body w e i g h t , a r e s u l t s e e m i n g l y i n c o n s i s t e n t w i t h t h e f a i l u r e of a n d r o g e n t r e a t m e n t t o i n f l u e n c e f o o d i n t a k e and body w e i g h t . F i n a l l y , i n an a t t e m p t t o g a i n some i n d i c a t i o n o f t h e e x t e n t of n a t u r a l d e f e m i n i z a t i o n o c c u r r i n g i n t h e male g e r b i l , t e s t s of l o r d o s i s b e h a v i o u r i n t h e male were c a r r i e d o u t a s w e l l . Method In o r d e r t h a t any e f f e c t s o b s e r v e d i n t h e male c o u l d be compared t o e f f e c t s seen i n t h e f e m a l e , i n i t i a t i o n of t h e f i v e t r e a t m e n t p h a s e s f o l l o w e d t h e t i m e c o u r s e o r i g i n a l l y s e t d u r i n g E x p e r i m e n t 9. F o r example, EB was a d m i n i s t e r e d t h e same number o f d a y s a f t e r s u r g e r y i n males as f o r f e m a l e s and c o n t i n u e d t h e same l e n g t h of t i m e b e f o r e Phase 3 s t a r t e d . However, i n m a l e s , t h e d e t r i m e n t a l e f f e c t s o f t h e 100 ^ ug EB d o s e were o b s e r v e d s o o n e r t h a n i n t h e f e m a l e s and t h u s , g r o u p E100 was t e r m i n a t e d b e f o r e t h e c o m p l e t i o n o f t h e EB ph a s e and was e l i m i n a t e d from a l l e x p e r i m e n t a l a n a l y s e s . A l l a n a l y s e s p e r f o r m e d were o t h e r w i s e i d e n t i c a l t o t h o s e done f o r E x p e r i m e n t 9. The r e s u l t i n g numbers o f a n i m a l s p e r g r o u p were 10 f o r g r o u p IC and E10 and 7 f o r g r o u p E1. Due t o e x c e e d i n g l y low l e v e l s o f r e c e p t i v i t y e x h i b i t e d by t h e male g e r b i l s g i v e n 1 o r 10 pq EB, no a n a l y s i s was p e r f o r m e d on t h e s e d a t a . 85 R e s u l t s and D i s c u s s i o n T h r e e day a v e r a g e s f o r f o o d i n a k e and body w e i g h t a r e p r e s e n t e d i n F i g u r e 11. An e x a m i n a t i o n of t h e d a t a f o r g r o u p s IC, E1, and E10 s u g g e s t s t h a t c a s t r a t i o n had a t r a n s i e n t f a c i l i t a t o r y e f f e c t on body w e i g h t and t h a t EB a d m i n i s t r a t i o n a p p e a r e d t o i n c r e a s e f o o d i n t a k e o n l y s l i g h t l y . A l t h o u g h c a s t r a t e s and c a s t r a t e s g i v e n EB t r e a t m e n t a p p e a r e d t o e a t more t h a n i n t a c t a n i m a l s , an a n a l y s i s o f v a r i a n c e i n d i c a t e d no s i g n i f i c a n t e f f e c t o f c a s t r a t i o n on f o o d i n t a k e . T h i s may have been due, i n p a r t , t o t h e w i t h i n s u b j e c t s n a t u r e of t h e d e s i g n . T h i s d e s i g n c o u l d have g r e a t l y i n c r e a s e d t h e v a r i a n c e when d i f f e r e n t t r e a t m e n t p h a s e s were c o l l a p s e d t o d e t e r m i n e an o v e r a l l c a s t r a t i o n e f f e c t . I n d e e d , a K r u s k a l - W a l l i s t e s t p e r f o r m e d on IC, E l , and E10 d a t a f o r P h a s e s 1 and 2 i n d i c a t e d a s i g n i f i c a n t o v e r a l l e f f e c t o f c a s t r a t i o n on f o o d i n t a k e Z = 4.68, g < 0.05. The a n a l y s i s of v a r i a n c e p e r f o r m e d on IC, E l , and E10 d a t a f o r P h a s e s 1 and 2 i n d i c a t e d a s i g n i f i c a n t e f f e c t o f p o i n t s , F ( 8 , 1 9 2 ) = 7.79, 2 < 0.0001. The g r o u p by p o i n t s i n t e r a c t i o n a p p r o a c h e d s i g n i f i c a n c e , F ( 1 6 , 1 9 2 ) = 1.66, 2 < 0.06. A n a l y s i s of body w e i g h t d a t a r e v e a l e d a s i g n i f i c a n t e f f e c t o f Phase, F ( 1 , 2 4 ) = 19.65, 2 = 0.0002, and a s i g n i f i c a n t e f f e c t of p o i n t s , F ( 8 , 1 9 2 ) = 2.98, 2 * 0.0004. F i g u r e 12 shows t h e r a t i o o f f o o d i n t a k e and body w e i g h t means f o r g r o u p E1 r e l a t i v e t o g r o u p IC e x p r e s s e d as a p e r c e n t a g e . E x a m i n a t i o n o f t h e d a t a f o r g r o u p s IC and E1 i n a l l p h a s e s o f t h e e x p e r i m e n t i n d i c a t e t h a t c a s t r a t i o n had o n l y a t r a n s i e n t e f f e c t on body w e i g h t and t h a t EB, EB + P, and p e r h a p s P t r e a t m e n t had no e f f e c t on body w e i g h t . F o o d i n t a k e l e v e l s > 86 F i g u r e 11. E f f e c t s o f c a s t r a t i o n and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n male g e r b i l s . Food i n t a k e and body w e i g h t were measured d a i l y and t h r e e day a v e r a g e s were r e c o r d e d . D a t a f o r i n t a c t c o n t r o l s (IC) and a n i m a l s r e c e i v i n g 1 j j g e s t r a d i o l b e n z o a t e (E1) d u r i n g e s t r a d i o l b e n z o a t e (EB) p h a s e s a r e p r e s e n t e d f o r a l l p h a s e s of t h e e x p e r i m e n t . F o r p r o g e s t e r o n e (P) p h a s e s , a do s e of 100 jug was u s e d . The ph a s e s e q u e n c e i s from t o p t o bo t t o m i n t h e f i g u r e . Food i n t a k e and body w e i g h t means f o r g r o u p E10 (10 jig EB) i s p r e s e n t e d f o r t h e f i r s t two p h a s e s of t h e e x p e r i m e n t . T h i s g r o u p was l a t e r d i s c o n t i n u e d when d e t r i m e n t a l e f f e c t s o f h i g h d o s e s of c h r o n i c EB were o b s e r v e d . Castration B S 3 82-I I I I I I I I I I I I I 12 15 18 21 24 27 30 33 36 39 42 45 48 I I I I I I I I 12 15 18 21 24 27 30 33 12 I I I I I I 15 18 21 24 27 30 Days co E TJ 71 £ 3 6 9 12 15 18 21 24 27 3C 10 9 a i i i i i i i i i i i 18 21 24 27 30 33 36 39 42 45 48 EB I 12 15 I I I I I I 18 21 24 27 30 33 EB + P 0 T 6 i — r 12 15 18 21 No Hormone T 6 12 15 18 21 Days 00 88 F i g u r e 12. E f f e c t s o f c a s t r a t i o n and o v a r i a n s t e r o i d a d m i n i s t r a t i o n on f o o d i n t a k e and body w e i g h t i n male g e r b i l s r e l a t i v e t o l e v e l s e x h i b i t e d by i n t a c t c o n t r o l a n i m a l s . D a i l y m e a sures of f o o d i n t a k e and body w e i g h t were a v e r a g e d t o c r e a t e f i v e d a t a p o i n t s p e r t r e a t m e n t p h a s e , p r e s e n t e d on t h e a b s c i s s a . The o r d i n a t e i s t h e r a t i o o f e x p e r i m e n t a l a n i m a l s c o r e s t o i n t a c t c o n t r o l a n i m a l s c o r e s , e x p r e s s e d as a p e r c e n t a g e . E s t r a d i o l b e n z o a t e (EB) and p r o g e s t e r o n e (P) d o s e s were 1 and 100 ^ug, r e s p e c t i v e l y . Castration 130 H 120 H 5 110-1 o 100 90 H 80 •= Weight 0= Intake 90 f o r E1 a n i m a l s were e l e v a t e d t h r o u g h o u t t h e e x p e r i m e n t . An a n a l y s i s o f v a r i a n c e r e v e a l e d a s i g n i f i c a n t g r o u p by p o i n t i n t e r a c t i o n f o r w e i g h t , F ( 2 0 , 3 0 0 ) = 3.37, p_ < 0.0001, and a s i g n i f i c a n t Phase by g r o u p i n t e r a c t i o n f o r f o o d i n t a k e , F (4,60) = 2.77, £ = 0.04, ( T a b l e 2 ) . F u r t h e r a n a l y s i s i n d i c a t e d t h a t E1 a n i m a l s w e ighed more t h a n IC a n i m a l s d u r i n g t h e f i r s t p o i n t of t h e c a s t r a t i o n p h a s e , p_ < 0.05. W e i g h t s o f IC and E1 a n i m a l s d i d not d i f f e r d u r i n g t h e EB and EB + P p h a s e s . However, b e g i n n i n g w i t h t h e f o u r t h p o i n t i n t h e P o n l y phase and c o n t i n u i n g t h r o u g h t h e s e c o n d p o i n t o f t h e P w i t h d r a w a l (no hormone) p h a s e , IC a n i m a l s w e i g h e d s i g n i f i c a n t l y more t h a n E1 a n i m a l s , £ < 0.05. By t h e f i n a l p o i n t i n t h e P w i t h d r a w a l p h a s e , t h i s had r e v e r s e d , w i t h IC a n i m a l s now w e i g h i n g l e s s t h a n E1 a n i m a l s , £ < 0.05. I t was f u r t h e r f o u n d t h a t f o o d i n t a k e f o r E1 a n i m a l s was s i g n i f i c a n t l y g r e a t e r t h a n t h a t o f c o n t r o l s d u r i n g t h e f i n a l phase of t h e e x p e r i m e n t , £ < 0.05, whereas t h e a n a l y s i s o f v a r i a n c e r e v e a l e d no s i g n i f i c a n t d i f f e r e n c e s i n f o o d i n t a k e d u r i n g t h e o t h e r f o u r p h a s e s . F i n a l l y , t h e r e were s i g n i f i c a n t e f f e c t s o f Phase f o r body w e i g h t , F ( 4 , 6 0 ) = 28.03, £ < 0.0001, and f o o d i n t a k e , F ( 4 , 6 0 ) = 6.05, £ = 0.0004, and o f p o i n t s f o r f o o d i n t a k e , F ( 2 0 , 3 0 0 ) = 4.69, £ < 0.0001. O v e r a l l , t h e s e r e s u l t s s u g g e s t t h a t c a s t r a t i o n may have o n l y a t e m p o r a r y e f f e c t on body w e i g h t . O v a r i a n s t e r o i d s a p p e a r e d t o e x e r t l i t t l e e f f e c t on f o o d i n t a k e and body w e i g h t w h i l e w i t h d r a w a l o f P may have s e r v e d t o i n c r e a s e f o o d i n t a k e above p o s t c a s t r a t i o n l e v e l s . 91 T a b l e 2. Mean f o o d i n t a k e and body w e i g h t i n male g e r b i l s as a f u n c t i o n of c a s t r a t i o n and o v a r i a n s t e r o i d t r e a t m e n t . PHASE CAST EB EB+P P NH BODY WEIGHT X ±SE 78.34 1.63 80.55 1.83 76.33 1.81 74.74 1.82 73.46 1.65 _ E1 X ±SE 79.78 0.95 81.62 1.01 77.20 0.95 72.60 1.14 72.82 0.98 FOOD INTAKE _ IC X ±SE 8.28 0.21 7.73 0.21 8.01 0.23 8.13 0.21 8.37 0.21 _ E1 X ±SE 8.82 0.24 8.57 0.27 8.99 0.26 9.03 0.39 10.37 0.29 IC = i n t a c t c o n t r o l a n i m a l s , r e c e i v e d no hormone t r e a t m e n t s . E1 = r e c e i v e d 1 jjq e s t r a d i o l b e n z o a t e (EB) d u r i n g EB p h a s e s and 100 jjq p r o g e s t e r o n e (P) d u r i n g P p h a s e s . NH = no hormone t r e a t m e n t . 92 GENERAL DISCUSSION The r e s u l t s of t h e p r e s e n t e x p e r i m e n t s i n d i c a t e t h a t f e m a l e g e r b i l s e x h i b i t a s i g n i f i c a n t d e c r e a s e i n f o o d i n t a k e and body w e i g h t a f t e r o v a r i e c t o m y w h i l e male g e r b i l s e x h i b i t a t r a n s i e n t i n c r e a s e i n body w e i g h t a f t e r c a s t r a t i o n . Maass & Wade (1977) o b s e r v e d a l o n g e r l a s t i n g i n c r e a s e i n body w e i g h t a f t e r c a s t r a t i o n . In a d d i t i o n , Maass & Wade (1977) o b s e r v e d no s i g n i f i c a n t e f f e c t o f c a s t r a t i o n on f o o d i n t a k e w h i l e t h e p r e s e n t r e s u l t s i n d i c a t e t h a t c a s t r a t i o n may have a d e l a y e d e f f e c t on f o o d i n t a k e . A d e l a y e d e f f e c t o f c a s t r a t i o n on b e h a v i o u r i s not u n u s u a l and has been r e p o r t e d f o r a l t e r a t i o n s i n f o o d i n t a k e and body w e i g h t i n male r a t s ( G e n t r y & Wade, 1976b) and f o r s e x u a l b e h a v i o u r i n male r a t s and g e r b i l s ( Y a h r , 1981). M o r e o v e r , t h e r e s t o r a t i v e e f f e c t s of TP t r e a t m e n t on b e h a v i o u r i n c a s t r a t e s a r e a l s o o f t e n d e l a y e d . I t i s p o s s i b l e t h a t t h e s e d e l a y s i n t h e b e h a v i o u r a l e f f e c t s o f c a s t r a t i o n and TP t r e a t m e n t a r e due t o a slow d e c l i n e and i n c r e a s e , r e s p e c t i v e l y , i n r e c e p t o r a c t i v i t y ( G o r z a l k a , p e r s o n a l c o m m u n i c a t i o n ) . O v a r i e c t o m i z e d f e m a l e g e r b i l s g i v e n c h r o n i c EB t r e a t m e n t e x h i b i t e d a d o s e - d e p e n d e n t i n c r e a s e i n f o o d i n t a k e and body w e i g h t , w i t h body w e i g h t e v e n t u a l l y r e a c h i n g t h a t o f i n t a c t c o n t r o l s . The E B - i n d u c e d i n c r e a s e i n f o o d i n t a k e and body w e i g h t i s c o n s i s t e n t w i t h t h e r e s u l t s o b t a i n e d by Maass & Wade (1977) f o r o v a r i e c t o m i z e d g e r b i l s . In a d d i t i o n , t h e p r e s e n t r e s u l t s a l s o i n d i c a t e t h a t t h e d e c r e a s e s i n f o o d i n t a k e and body w e i g h t o b s e r v e d a f t e r o v a r i e c t o m y a r e due t o t h e r e m o v a l o f endogenous e s t r o g e n s and t h a t EB t r e a t m e n t s e r v e s a r e s t o r a t i v e 93 f u n c t i o n . C a s t r a t e d male g e r b i l s , on t h e o t h e r hand, e x h i b i t e d no s i g n i f i c a n t a l t e r a t i o n s i n f o o d i n t a k e o r body w e i g h t i n r e s p o n s e t o EB t r e a t m e n t . A l t h o u g h a d m i n i s t r a t i o n of P i n c o n j u n c t i o n w i t h EB p r o d u c e d no s i g n i f i c a n t a l t e r a t i o n s i n f e m a l e body w e i g h t , i t d i d p r o d u c e a s i g n i f i c a n t d e c r e a s e i n f o o d i n t a k e , a r e s u l t c o n s i s t e n t w i t h t h a t of Maass & Wade ( 1 9 7 7 ) . T h i s s u g g e s t s t h a t p r o g e s t e r o n e , g i v e n i n c o n j u n c t i o n w i t h EB, may a l t e r m e t a b o l i c a c t i v i t y , t h u s n e c e s s i t a t i n g g r e a t e r f o o d i n t a k e f o r t h e m a i n t e n a n c e of body w e i g h t . The p r e s e n t r e s u l t s f u r t h e r e x t e n d t h e f i n d i n g s o f Maass & Wade (1977) by i n d i c a t i n g t h a t t h e a d m i n i s t r a t i o n o f EB a l o n e i s s u f f i c i e n t t o r e s t o r e b o t h f o o d i n t a k e and body w e i g h t of o v a r i e c t o m i z e d a n i m a l s t o l e v e l s e x h i b i t e d by i n t a c t c o n t r o l s . I n d e e d , t h e f u r t h e r i n c r e a s e i n f o o d i n t a k e o b s e r v e d i n a n i m a l s a l s o r e c e i v i n g p r o g e s t e r o n e i s not n e c e s s a r y f o r t h e r e s t o r a t i o n of body w e i g h t t o c o n t r o l l e v e l s . I n t h e male g e r b i l , a d m i n i s t r a t i o n o f P i n c o n j u n c t i o n w i t h EB had no s i g n i f i c a n t e f f e c t on f o o d i n t a k e and body w e i g h t . T r e a t m e n t o f o v a r i e c t o m i z e d f e m a l e s w i t h P a l o n e r e s u l t e d i n d e c r e a s e d body w e i g h t w h i l e f o o d i n t a k e r e m a i n e d above l e v e l s e x h i b i t e d by c o n t r o l a n i m a l s . F u r t h e r a n a l y s i s s u g g e s t e d t h a t t h e d e c r e a s e i n body w e i g h t m i g h t be due, i n p a r t , t o t h e p r i o r r e m o v a l o f EB. T h i s p o s s i b i l i t y was s t r e n g t h e n e d by t h e f i n d i n g t h a t t h e w i t h d r a w a l of P d i d n o t l e a d t o a s i g n i f i c a n t i n c r e a s e i n body w e i g h t , w h i c h one would e x p e c t i f P a d m i n i s t r a t i o n was r e s p o n s i b l e f o r t h e d e c r e a s e i n body w e i g h t . F e m a l e s d i d , however, e x h i b i t a r e t u r n t o no r m a l l e v e l s o f f o o d i n t a k e a f t e r 94 P w i t h d r a w a l , i n d i c a t i n g t h a t p r o g e s t e r o n e may have been p a r t i a l l y r e s p o n s i b l e f o r t h e e l e v a t e d f o o d i n t a k e l e v e l s d u r i n g t h e P o n l y p h a s e . U n l i k e t h e e f f e c t o b s e r v e d i n t h e f e m a l e g e r b i l , d e c r e a s e d body w e i g h t i n t h e male g e r b i l d u r i n g t h e P o n l y phase d i d not a p p e a r t o be due t o t h e r e m o v a l of EB. R a t h e r , t h e d e c r e a s e i n body w e i g h t a p p e a r e d t o be due s o l e l y t o an e f f e c t o f P t r e a t m e n t . T h i s i s s u p p o r t e d by t h e f i n d i n g t h a t , i n m a l e s , w i t h d r a w a l o f P l e d t o a g r a d u a l i n c r e a s e i n body w e i g h t , e v e n t u a l l y t o l e v e l s above t h o s e o f c o n t r o l s . An a n a l y s i s o f v a r i a n c e i n d i c a t e d t h a t t h e w i t h d r a w a l o f p r o g e s t e r o n e a l s o l e d t o s i g n i f i c a n t l y g r e a t e r f o o d i n t a k e i n male g e r b i l s , a r e s u l t o p p o s i t e o f t h a t o b s e r v e d i n f e m a l e s . However, t h e g e n e r a l e l e v a t i o n of f o o d i n t a k e i n male c a s t r a t e s t h r o u g h o u t t h e e x p e r i m e n t makes t h i s r e s u l t d i f f i c u l t t o i n t e r p r e t . T h e r e i s no i n d i c a t i o n t h a t P a d m i n i s t r a t i o n was h a v i n g any more e f f e c t on f o o d i n t a k e and body w e i g h t t h a n EB o r EB + P, t r e a t m e n t s w h i c h t h e m s e l v e s a p p e a r e d t o have l i t t l e e f f e c t . Y e t , t h e w i t h d r a w a l o f P a p p a r e n t l y l e d t o f u r t h e r i n c r e a s e s i n f o o d i n t a k e even t h o u g h i t s a d m i n i s t r a t i o n d i d n o t a p p e a r t o d e c r e a s e f o o d i n t a k e . I t i s p o s s i b l e t h a t o v a r i a n s t e r o i d s were e x e r t i n g a s l i g h t i n h i b i t o r y e f f e c t t h a t was masked by ( o r was m a s k i n g ) a d e l a y e d e f f e c t o f c a s t r a t i o n . I f s o , i t would n o t be t h e w i t h d r a w a l o f P p e r se t h a t l e d t o a l t e r a t i o n s i n f o o d i n t a k e and body w e i g h t . R a t h e r , i t would be t h e c o m p l e t e w i t h d r a w a l o f a l l o v a r i a n s t e r o i d s t h a t p r o d u c e d t h e e f f e c t s . T h i s t y p e o f i n h i b i t i o n m i g h t a l s o h e l p e x p l a i n t h e r a t h e r u n u s u a l r e s u l t o b t a i n e d by Maass & Wade ( 1 9 7 7 ) . They f o u n d t h a t t h e 95 a d m i n i s t r a t i o n of TP t o c a s t r a t e d male g e r b i l s p r o d u c e d no o b s e r v a b l e a l t e r a t i o n i n f o o d i n t a k e o r body w e i g h t . However, when Maass & Wade (1977) c e a s e d TP t r e a t m e n t , body w e i g h t i n c r e a s e d . P r e s u m a b l y , t h e d e l a y e d e f f e c t s o f c a s t r a t i o n i n e i t h e r e x p e r i m e n t would have been an i n c r e a s e i n f o o d i n t a k e a n d / o r body w e i g h t i f s t e r o i d t r e a t m e n t s had n o t been i n i t i a t e d . The f i n d i n g t h a t o v a r i e c t o m y d e c r e a s e d and EB t r e a t m e n t i n c r e a s e d f o o d i n t a k e and body w e i g h t i n t h e f e m a l e g e r b i l i s o f g r e a t i n t e r e s t i n r e l a t i o n t o r e s u l t s o b t a i n e d f o r o t h e r r o d e n t s p e c i e s . In o t h e r f e m a l e r o d e n t s , o v a r i e c t o m y has been f o u n d t o i n c r e a s e f o o d i n t a k e and body w e i g h t ( G e r a l l & T h i e l , 1975; M o r i n & Flemming, 1978; S l o b e t a l . , 1973; T a r t t e l i n & G o r s k i , 1973; Wade, 1975; Wade & Z u c k e r , 1970; W r i g h t & T u r n e r , 1973). In a d d i t i o n , p r o g e s t e r o n e has been f o u n d t o a t t e n u a t e r a t h e r t h a n f a c i l i t a t e t h e e f f e c t s of EB on f o o d i n t a k e and body w e i g h t ( s e e Wade, 1976, f o r a r e v i e w ) . Thus, t h e f e m a l e g e r b i l i s q u i t e d i f f e r e n t f r o m o t h e r f e m a l e r o d e n t s s t u d i e d t o d a t e w i t h r e s p e c t t o t h e h o r m o n a l m e d i a t i o n of f o o d i n t a k e and body w e i g h t . The s t u d y of t h e s e d i f f e r e n c e s may a i d i n r e f i n i n g p r e s e n t m o d e l s o f t h e h o r m o n a l m e d i a t i o n o f f o o d i n t a k e and body w e i g h t i n r o d e n t s . M a l e g e r b i l s e x h i b i t e d a t e m p o r a r y i n c r e a s e i n body w e i g h t a f t e r c a s t r a t i o n . T h i s i s somewhat s i m i l a r t o t h e e f f e c t o b s e r v e d i n t h e male h a m s t e r , w h i c h a l s o e x h i b i t s a w e i g h t i n c r e a s e a f t e r c a s t r a t i o n ( K o w a l e w s k i , 1969). However, i n t h e c a s t r a t e d male h a m s t e r , TP t r e a t m e n t r e d u c e s b o t h f o o d i n t a k e and body w e i g h t ( Z u c k e r e t a l . , 1972) w h i l e i n t h e c a s t r a t e d male g e r b i l , i t does not (Maass & Wade, 1977). Thus, a l t h o u g h 96 a n d r o g e n s may be t h e p r i m a r y a c t i v a t i n g hormones f o r t h e r e g u l a t i o n o f f o o d i n t a k e and body w e i g h t i n t h e h a m s t e r (as s u g g e s t e d by Wade, 1976), t h i s i s not t h e c a s e i n t h e male g e r b i l . The f i n d i n g s of Maass & Wade (1977) r e s u l t e d i n t h e p r e s e n t s u g g e s t i o n t h a t p e r h a p s t h e h o r m o n a l m e d i a t i o n o f f o o d i n t a k e and body w e i g h t i n t h e g e r b i l i s s i m i l a r t o t h a t o b s e r v e d i n t h e r a t , where o v a r i a n s t e r o i d s , r a t h e r t h a n a n d r o g e n s , a r e t h e p r i m a r y h o r m o n a l r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t (Wade, 1976). R e c a l l t h a t , i n t h e r a t , t h e f o l l o w i n g e v i d e n c e s u p p o r t s t h e c o n c l u s i o n t h a t o v a r i a n s t e r o i d s a r e t h e p r i m a r y h o r m o n a l r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t . F i r s t , low d o s e s o f TP i n c r e a s e , w h i l e h i g h d o s e s o f TP d e c r e a s e f o o d i n t a k e and body w e i g h t i n male c a s t r a t e s . T h i s i s c o n s i s t e n t w i t h t h e s u g g e s t i o n t h a t h i g h e r d o s e s o f TP would r e s u l t i n more a r o m a t i z a t i o n t o e s t r o g e n , a s s u m i n g a r o m a t i z i n g enzyme s u f f i c i e n c y . S e cond, P a t t e n u a t e s t h e e f f e c t s o f h i g h TP d o s e s i n male c a s t r a t e s , s u g g e s t i n g t h a t P may be a t t e n u a t i n g t h e e f f e c t of e s t r o g e n d e r i v e d from TP. F i n a l l y , EB p r o d u c e s d e c r e a s e s i n f o o d i n t a k e and body w e i g h t i n o v a r i e c t o m i z e d f e m a l e s w h i l e P a t t e n u a t e s t h i s e f f e c t . The p r e s e n t r e s u l t s i n d i c a t e t h a t o v a r i a n s t e r o i d s may have some e f f e c t i n t h e male g e r b i l b u t i t i s u n c e r t a i n a s t o w h i c h sex s t e r o i d s a r e t h e p r i m a r y r e g u l a t o r s of f o o d i n t a k e and body w e i g h t i n t h e male g e r b i l . I n t h e f e m a l e g e r b i l , o v a r i a n s t e r o i d s do e x e r t a c l e a r and s i g n i f i c a n t e f f e c t and i t seems l i k e l y t h a t t h e y p l a y a major r o l e i n t h e hor m o n a l m e d i a t i o n o f f o o d i n t a k e and body w e i g h t . R e s e a r c h on t h e h o r m o n a l m e d i a t i o n of f o o d i n t a k e i n t h e 97 r a t i n d i c a t e s t h a t t h e e f f e c t s o f o v a r i e c t o m y and EB t r e a t m e n t on f o o d i n t a k e and body w e i g h t may be due, i n p a r t , t o e s t r o g e n -i n d u c e d a l t e r a t i o n s i n b r a i n c a t e c h o l a m i n e l e v e l s (Bapna, N e f f , & C o s t a , 1971; C r o w l e y , O'Donohue, W a s c h s l i c h t & J a c o b o w i t s , 1978; H o e b e l , 1971; Simpson & D i c a r a , 1973; van d e r Gugten & S l a n g e n , 1975). In g e n e r a l , i t has been f o u n d t h a t t h e a d m i n i s t r a t i o n o f dopamine (DA) o r low d o s e s o f n o r e p i n e p h r i n e (NE) p r o d u c e i n c r e a s e s i n f o o d i n t a k e w h i l e DA and NE a n t a g o n i s t s b l o c k o r r e v e r s e t h i s e f f e c t ( C l i n e s c h m i d t , M c G u f f i n , & Werner, 1974; H o e b e l , 1971, 1977). O v a r i e c t o m y has been f o u n d t o i n c r e a s e s y n t h e s i s o f NE i n t h e h y p o t h a l a m u s ( A n t o n - T a y & Wurtman, 1968; Bapna e t a l . , 1971) w h i l e EB a d m i n i s t r a t i o n has been f o u n d t o d e c r e a s e h y p o t h a l a m i c NE s y n t h e s i s (Bapna e t a l . , 1971). Simpson & D i c a r a (1973) f o u n d t h a t DA i n c r e a s e d f o o d i n t a k e o n l y when EB l e v e l s were low w h i l e NE i n c r e a s e d f o o d i n t a k e l e v e l s i n d e p e n d e n t of EB l e v e l s . T h i s l e d them t o s u g g e s t t h a t EB m i g h t i n t e r f e r e w i t h dopamine-yS-h y d r o x y l a s e , t h e enzyme w h i c h c o n v e r t s DA t o NE. T h i s would l e a d t o d e c r e a s e d b r a i n NE and a c o r r e s p o n d i n g d e c r e a s e i n f o o d i n t a k e (Simpson & D i c a r a , 1973). In t h e f e m a l e g e r b i l , t h e i n c r e a s e i n f o o d i n t a k e and body w e i g h t i n r e s p o n s e t o EB a d m i n i s t r a t i o n i s t h e o p p o s i t e o f t h e e f f e c t o b s e r v e d i n t h e f e m a l e r a t . I f , i n t h e f e m a l e r a t , EB d e c r e a s e s f o o d i n t a k e by i n t e r f e r i n g w i t h t h e c o n v e r s i o n o f DA t o NE, i t would s u g g e s t t h a t t h e o p p o s i t e e f f e c t i n t h e f e m a l e g e r b i l c o u l d be due t o a t l e a s t one o f t h r e e mechanisms. F i r s t , EB may f a c i l i t a t e r a t h e r t h a n i n h i b i t DA t o NE c o n v e r s i o n , r e s u l t i n g i n h i g h e r NE l e v e l s t h a t would l e a d t o i n c r e a s e d 98 l e v e l s of f o o d i n t a k e . S e c o n d , NE may e x e r t an i n h i b i t o r y r a t h e r t h a n f a c i l i t a t o r y e f f e c t on f o o d i n t a k e i n t h e g e r b i l . T h u s , i f EB i n h i b i t e d DA t o NE c o n v e r s i o n , NE l e v e l s w ould d e c r e a s e and f o o d i n t a k e would i n c r e a s e . T h i r d , EB may be e x e r t i n g i t s e f f e c t s on o t h e r n e u r o t r a n s m i t t e r s . To t h e b e s t of my knowledge, r e l e v a n t d a t a t o s e p a r a t e t h e s e p o t e n t i a l mechanisms i s n o t a v a i l a b l e . R e l a t i v e l y l i t t l e work has been done on t h e e f f e c t s of c a s t r a t i o n and EB t r e a t m e n t on b r a i n n e u r o t r a n s m i t t e r l e v e l s i n t h e c a s t r a t e d male r a t . Donoso, S t e f a n o , B i s c a r d i , & C u k i e r (1967) f o u n d t h a t c a s t r a t i o n i n male r a t s l e d t o i n c r e a s e d h y p o t h a l a m i c DA c o n c e n t r a t i o n s , p r o d u c i n g a h i g h e r NE:DA r a t i o . T h u s , i n c r e a s e d NE, d e c r e a s e d DA, a n d / o r an a l t e r e d NE:DA r a t i o c o u l d be r e s p o n s i b l e f o r t h e o b s e r v e d d e c r e a s e i n f o o d i n t a k e and body w e i g h t i n t h e c a s t r a t e d male r a t . A l t h o u g h i t i s d i f f i c u l t t o d e t e r m i n e t h e e x a c t n a t u r e of t h e e f f e c t s o f c a s t r a t i o n i n t h e male g e r b i l , i t seems p l a u s i b l e t h a t a t l e a s t some o f t h e e f f e c t s w o u l d be m e d i a t e d by hormone-i n d u c e d a l t e r a t i o n s i n c a t e c h o l a m i n e l e v e l s . S i n c e t h e male g e r b i l a p p e a r s t o e x h i b i t a f o o d i n t a k e and body w e i g h t i n c r e a s e a f t e r c a s t r a t i o n w h i l e t h e male r a t e x h i b i t s a d e c r e a s e , one mig h t a g a i n s u s p e c t t h a t t h e e f f e c t s o f c a s t r a t i o n on n e u r o t r a n s m i t t e r l e v e l s , o r t h e e f f e c t s o f n e u r o t r a n s m i t t e r s , d i f f e r between t h e s e s p e c i e s . C a s t r a t i o n i n t h e male g e r b i l may d e c r e a s e , r a t h e r t h a n i n c r e a s e NE l e v e l s , a n d / o r i n c r e a s e , r a t h e r t h a n d e c r e a s e , DA l e v e l s . E i t h e r would p r o d u c e a l o w e r r a t h e r t h a n h i g h e r NE:DA r a t i o and m i g h t be r e s p o n s i b l e f o r t h e i n c r e a s e s i n f o o d i n t a k e and body w e i g h t seen i n t h e male g e r b i l 99 a f t e r c a s t r a t i o n . A l t e r n a t i v e l y , t h e e f f e c t s of c a s t r a t i o n on NE and DA l e v e l s i n t h e male g e r b i l may be s i m i l a r t o t h o s e o b s e r v e d i n t h e male r a t w h i l e t h e a c t i o n of t h e n e u r o t r a n s m i t t e r s may d i f f e r between t h e s e s p e c i e s . F i n a l l y , c a s t r a t i o n may a l t e r t h e l e v e l o f some o t h e r n e u r o t r a n s m i t t e r . E x p e r i m e n t s 4, 11, and 12 i n d i c a t e d t h a t , w h i l e c a s t r a t e d male g e r b i l s e x h i b i t e d e s s e n t i a l l y no f e m a l e s e x u a l b e h a v i o u r d u r i n g c h r o n i c EB a d m i n i s t r a t i o n , f e m a l e g e r b i l s e x h i b i t e d h i g h l e v e l s o f r e c e p t i v i t y when g i v e n 100 ^ug EB/day. Doses of 1 and 10 j j g EB/day l e d t o m o d e r a t e r e c e p t i v i t y . T h u s , a l t h o u g h b o t h 1 and 10 pq EB/day were s u f f i c i e n t f o r t h e r e s t o r a t i o n of f o o d i n t a k e and body w e i g h t t o c o n t r o l l e v e l s , t h e s e d o s e s were not c a p a b l e o f e l i c i t i n g h i g h l e v e l s o f r e c e p t i v i t y . T h i s i s i n c o n t r a s t t o t h e f e m a l e r a t where c h r o n i c a d m i n i s t r a t i o n o f l e s s t h a n 1 ^ug EB/day ca n e l i c i t h i g h l e v e l s of r e c e p t i v i t y ( D a v i d s o n e t a l . , 1968; G o r z a l k a & R a i b l e , 1981; G r a y & G o r z a l k a , 1980) as w e l l as s i g n i f i c a n t l y a l t e r f o o d i n t a k e and body w e i g h t (Landau & Z u c k e r , 1976; Wade, 1975). I t would a p p e a r t h a t t h e n e u r a l s u b s t r a t e r e g u l a t i n g s e x u a l r e s p o n d i n g i n t h e f e m a l e g e r b i l i s l e s s s e n s i t i v e t o EB t h a n t h a t o f t h e f e m a l e r a t . In a d d i t i o n , t h e marked d i f f e r e n c e s i n s e n s i t i v i t y t o e s t r o g e n seen between t h e s y s t e m r e g u l a t i n g f o o d i n t a k e and body w e i g h t and t h e s y s t e m r e g u l a t i n g s e x u a l r e s p o n d i n g i n t h e g e r b i l i s n o t a p p a r e n t i n t h e f e m a l e r a t . The d i f f e r e n t i a l EB s e n s i t i v i t i e s o f t h e two s y s t e m s i n t h e g e r b i l and r a t may m e r e l y r e f l e c t t h e f a c t t h a t s e x u a l r e c e p t i v i t y i s n o r m a l l y more p r o g e s t e r o n e - d e p e n d e n t i n t h e g e r b i l ( E x p e r i m e n t s 2 - 4 ) . M a l e g e r b i l s d i d n o t e x h i b i t s i g n i f i c a n t f e m a l e s e x u a l 100 b e h a v i o u r when g i v e n c h r o n i c EB t r e a t m e n t . T h i s i s i n c o n t r a s t t o t h e male r a t w h i c h w i l l show low l e v e l s o f f e m a l e s e x u a l b e h a v i o u r when g i v e n c h r o n i c EB t r e a t m e n t i n d o s e s s u c h a s 20 j j g / k g / d a y ( E r i k s s o n & S o d e r s t e n , 1973). The 10 j j g EB dose u s e d i n t h e p r e s e n t e x p e r i m e n t s r e p r e s e n t s a dose of a b o u t 120 j j g / k g / d a y . A l t h o u g h t h i s d o s e i s s u b s t a n t i a l l y l a r g e r t h a n t h a t u s e d by E r i k s s o n & S o d e r s t e n ( 1 9 7 3 ) , i t f a i l e d t o e l i c i t any a p p r e c i a b l e l e v e l o f s e x u a l r e c e p t i v i t y i n male g e r b i l s . T h i s i n d i c a t e s t h a t male g e r b i l s a r e n a t u r a l l y d e f e m i n i z e d d u r i n g t h e p e r i o d o f s e x u a l d i f f e r e n t i a t i o n . F u r t h e r m o r e , endogenous a n d r o g e n s a p p e a r t o d e f e m i n i z e t h e male g e r b i l t o a g r e a t e r e x t e n t t h a n t h e y do t h e male r a t . I t a l s o a p p e a r s t h a t b o t h male and f e m a l e g e r b i l s a r e l e s s s e n s i t i v e t h a n male a n d f e m a l e r a t s t o t h e e f f e c t s o f EB on s e x u a l r e s p o n d i n g . T h i s a g a i n i n d i c a t e s t h a t t h e h o r m o n a l r e g u l a t i o n o f s e x u a l r e c e p t i v i t y i n t h e g e r b i l may be more l i k e t h a t o b s e r v e d i n t h e h a m s t e r , w h i c h a l s o e x h i b i t s l e s s s e n s i t i v i t y t o EB and i s more p r o g e s t e r o n e - d e p e n d e n t t h a n t h e r a t ( F e d e r e t a l . , 1974). In summary, o v a r i a n s t e r o i d s were f o u n d t o e x e r t a majo r e f f e c t on f o o d i n t a k e and body w e i g h t i n t h e f e m a l e g e r b i l whereas t h e e f f e c t s o f o v a r i a n s t e r o i d s on f o o d i n t a k e and body w e i g h t i n t h e male g e r b i l r e m a i n u n c l e a r . In t h e f e m a l e g e r b i l , EB t r e a t m e n t a p p e a r s t o s e r v e a r e s t o r a t i v e f u n c t i o n i n t h e o v a r i e c t o m i z e d a n i m a l , b r i n g i n g f o o d i n t a k e and body w e i g h t back t o p r e s u r g i c a l l e v e l s . I t i s p o s s i b l e t h a t t h e e f f e c t s o f EB on f o o d i n t a k e and body w e i g h t i n t h e g e r b i l a r e p r o d u c e d by h o r m o n e - i n d u c e d a l t e r a t i o n s i n b r a i n c a t e c h o l a m i n e l e v e l s , a s may be t h e c a s e i n t h e r a t . The p r e s e n t r e s u l t s a l s o i n d i c a t e 101 t h a t t h e s y s t e m r e g u l a t i n g f o o d i n t a k e and body w e i g h t i n t h e g e r b i l i s more s e n s i t i v e t o e s t r o g e n than t h e s y s t e m r e g u l a t i n g f e m a l e s e x u a l b e h a v i o u r . F i n a l l y , t h e r e s u l t s s u g g e s t t h a t e xogenous q u a n t i t i e s of e s t r o g e n w h i c h i n d u c e r e c e p t i v i t y i n male and f e m a l e r a t s a r e i n s u f f i c i e n t t o i n d u c e r e c e p t i v i t y i n male and f e m a l e g e r b i l s . I t seems l i k e l y t h a t o v a r i a n s t e r o i d s p l a y a major r o l e i n t h e h o r m o n a l m e d i a t i o n of f o o d i n t a k e and body w e i g h t i n t h e f e m a l e g e r b i l . A l t h o u g h t h e r e s u l t s of E x p e r i m e n t 10 and t h o s e o b t a i n e d by Maass & Wade (1977) s u g g e s t t h a t t h e h o r m o n a l r e g u l a t i o n of f o o d i n t a k e and body w e i g h t i n t h e male g e r b i l may d i f f e r from t h a t o b s e r v e d i n o t h e r male r o d e n t s e xamined so f a r , a g r e a t d e a l of f u r t h e r s t u d y w i l l be r e q u i r e d b e f o r e t h e mechanisms u n d e r l y i n g t h e s e d i f f e r e n c e s can be d e t e r m i n e d . l i b - P r e - and N e o n a t a l T e s t o s t e r o n e P r o p i o n a t e E x p o s u r e ;  E f f e c t s on M a l e and Female S e x u a l B e h a v i o u r i n A d u l t h o o d S i n c e P h o e n i x e t a l . , (1959) f i r s t s u g g e s t e d t h a t sex s t e r o i d s c o u l d e x e r t b o t h an o r g a n i z a t i o n a l as w e l l a s an a c t i v a t i o n a l e f f e c t on t h e b r a i n , a g r e a t w e a l t h of e v i d e n c e has a c c u m u l a t e d i n s u p p o r t o f t h i s h y p o t h e s i s . A c t i v a t i o n a l e f f e c t s a r e s e e n not o n l y i n t h e hormonal r e g u l a t i o n o f s e x u a l b e h a v i o u r but a l s o i n t h e m e d i a t i o n of e a t i n g b e h a v i o u r , a g g r e s s i o n , s c e n t m a r k i n g , and a wide v a r i e t y o f o t h e r b e h a v i o u r s , a l l o f w h i c h a r e a l t e r e d by gonadectomy i n a d u l t h o o d ( G o r s k i , 1979). Much o f t h e s u p p o r t f o r t h e o r g a n i z a t i o n a l e f f e c t s o f sex s t e r o i d s has been more r e c e n t and i t i s now c l e a r t h a t a d u l t s e x u a l b e h a v i o u r , a s w e l l as a v a r i e t y of o t h e r b e h a v i o u r s , i s 1 02 i n f l u e n c e d by t h e h o r m o n a l e n v i r o n m e n t d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n ( f o r r e v i e w s , see F e d e r & Wade, 1974; G o r s k i , 1971, 1979, 1980; Goy, 1970; McEwen, De n e f , G e r l a c h , & P l a p i n g e r , 1974). In t h e g e n e t i c male, a n d r o g e n s e c r e t i o n s ( p r i m a r i l y t e s t o s t e r o n e ) have been f o u n d t o : (1) g u i d e s e x u a l d i f f e r e n t i a t i o n of male r e p r o d u c t i v e o r g a n s and i n c r e a s e t h e s e n s i t i v i t y o f t h e s e t i s s u e s and t h e b r a i n t o a n d r o g e n s i n a d u l t h o o d , (2) a c t on t h e h y p o t h a l a m u s t o p r o d u c e a t o n i c , r a t h e r t h a n c y c l i c , p a t t e r n o f g o n a d o t r o p i n r e l e a s e i n a d u l t h o o d , and (3) d e c r e a s e t h e r e s p o n s i v e n e s s o f t i s s u e s m e d i a t i n g s e x u a l b e h a v i o u r i n a d u l t h o o d t o e s t r a d i o l and p r o g e s t e r o n e ( F e d e r & Wade, 1974; G o r s k i , 1980; Goy, 1970). In g e n e t i c f e m a l e s , t h e a b s e n c e o f a n d r o g e n s p e r m i t s f e m a l e r e p r o d u c t i v e o r g a n s t o d e v e l o p , g o n a d o t r o p i n s t o be r e l e a s e d c y c l i c a l l y ( t h e e s t r o u s c y c l e ) , a nd t h e t i s s u e s m e d i a t i n g s e x u a l b e h a v i o u r t o be h i g h l y s e n s i t i v e t o e s t r o g e n and p r o g e s t e r o n e ( F e d e r & Wade, 1974; F l e r k o , Mess & I l l e i - D o n h o f f e r , 1969; G o r s k i , 1980). The t e r m ' d e f e m i n i z a t i o n 1 was i n i t i a l l y u s e d by Whalen i n r e f e r e n c e t o t h e p r o f o u n d d e c r e a s e i n e s t r o g e n s e n s i t i v i t y t h a t o c c u r s when a n d r o g e n s a r e p r e s e n t d u r i n g t h e p e r i o d o f s e x u a l d i f f e r e n t i a t i o n (Whalen & Edwards, 1967; Whalen, L u t t g e , & G o r z a l k a , 1971). The te r m ' m a s c u l i n i z a t i o n ' i d e a l l y , b u t not a l w a y s , r e f e r s t o t h e p r e s e n c e o f a l l t h r e e components o f male s e x u a l r e s p o n d i n g (mounts w i t h p e l v i c t h r u s t i n g , i n t r o m i s s i o n , and e j a c u l a t i o n s ) . When r e v i e w i n g t h e l i t e r a t u r e on t h e e f f e c t s o f e a r l y 1 03 h o r m o n a l e n v i r o n m e n t on a d u l t s e x u a l b e h a v i o u r , i t became c l e a r t o t h e a u t h o r t h a t t h e t e r m s ' m a s c u l i n i z e d ' and ' d e f e m i n i z e d ' were f r e q u e n t l y c o n f u s e d w i t h e a c h o t h e r and u s e d i n a p p r o p r i a t e l y . An a n i m a l w h i c h e x h i b i t s a d e c l i n e i n s e x u a l r e c e p t i v i t y i s o n l y d e f e m i n i z e d i f t h e r e d u c t i o n i n s e x u a l r e c e p t i v i t y i s p r o n o u n c e d , s u c h t h a t o n l y v e r y low l e v e l s o f r e c e p t i v i t y a r e o b s e r v e d . A l t h o u g h t h e t e r m ' d e f e m i n i z e d ' - i s g e n e r a l l y u s e d a p p r o p r i a t e l y i n t h e r a t , mouse, and g u i n e a p i g l i t e r a t u r e , i t i s f r e q u e n t l y m i s u s e d i n t h e h a m s t e r l i t e r a t u r e . The male h a m s t e r e x h i b i t s f a i r l y h i g h l e v e l s o f f e m a l e s e x u a l b e h a v i o u r i n a d u l t h o o d and i s c o n s i d e r e d , p r o p e r l y , t o be t h e one r o d e n t examined so f a r t h a t i s n o t d e f e m i n i z e d by a n d r o g e n s d u r i n g s e x u a l d i f f e r e n t i a t i o n (Goldman, 1978; T i e f e r & J o h n s o n , 1975). D e s p i t e t h i s , s e v e r a l a u t h o r s ( e . g . Baum, 1979; C a r t e r C l emens, & Hoekema, 1972; T i e f e r & J o h n s o n , 1975), upon f i n d i n g t h a t n e o n a t a l a n d r o g e n t r e a t m e n t r e s u l t s i n a male p a t t e r n o f s e x u a l b e h a v i o u r i n t h e f e m a l e h a m s t e r , c o n c l u d e t h a t t h e f e m a l e h a m s t e r i_s d e f e m i n i z e d by n e o n a t a l a n d r o g e n s . T h i s seems t o be an u n r e a s o n a b l e c o n c l u s i o n s i n c e t h e TP t r e a t e d f e m a l e h a m s t e r e x h i b i t s t h e same d e g r e e o f f e m a l e s e x u a l b e h a v i o u r as does t h e male h a m s t e r , and t h a t l e v e l i s s u f f i c i e n t t o i n d i c a t e t h e h a m s t e r i s n o t d e f e m i n i z e d a l t h o u g h i t is m a s c u l i n i z e d . T h i s a l s o c l e a r l y i n d i c a t e s t h a t m a s c u l i n i z a t i o n and d e f e m i n i z a t i o n need n o t be c o n c u r r e n t . As s t a t e d e a r l i e r , t h e t e r m ' m a s c u l i n i z a t i o n ' i s b e s t u s e d t o r e f e r o n l y t o an a n i m a l w h i c h e x h i b i t s a l l components of male s e x u a l b e h a v i o u r . T h e r e a r e s e v e r a l good r e a s o n s f o r t h i s r e s t r i c t i o n . F o r example, n o r m a l f e m a l e r a t s w i l l e x h i b i t 104 m o u n t i n g b e h a v i o u r i n t h e a b s e n c e of exogenous a n d r o g e n s (Baum, 1979; P l a p i n g e r & McEwen, 1978). F u r t h e r m o r e , n e o n a t a l c a s t r a t i o n o f male r a t s does n o t e l i m i n a t e m o u n t i n g b e h a v i o u r i n a d u l t h o o d (Goldman, 1978). Thus, m o u n t i n g b e h a v i o u r i s not a g e n d e r - s p e c i f i c r e s p o n s e , does n o t seem h i g h l y d e p e n d e n t upon t h e i n f l u e n c e of p e r i n a t a l a n d r o g e n s and t h e r e f o r e i s not an a d e q u a t e i n d i c a t o r of b e h a v i o u r a l m a s c u l i n i z a t i o n . On t h e o t h e r hand, i n t r o m i s s i o n s and e j a c u l a t i o n s a r e r a r e l y e x h i b i t e d by g e n e t i c f e m a l e s and n e o n a t a l c a s t r a t i o n of m a l e s does e l i m i n a t e i n t r o m i t t i n g and e j a c u l a t o r y b e h a v i o u r (Goldman, 1978), s u g g e s t i n g t h a t t h e y a r e g e n d e r - s p e c i f i c r e s p o n s e s t h a t a r e d e p e n d e n t upon e a r l y a n d r o g e n s . F u r t h e r m o r e , a l t h o u g h a TP t r e a t e d g e n e t i c f e m a l e may be p h y s i o l o g i c a l l y i n c a p a b l e of i n t r o m i t t i n g and e j a c u l a t i n g , she i s b e h a v i o u r a l l y c a p a b l e of e x h i b i t i n g t h e s e r e s p o n s e s ( C o n i g l i o & Clemens, 1976; G e r a l l & Ward, 1966; N a d l e r , 1969). Male r a t s e x h i b i t v e r y s t e r e o t y p i c a l r e s p o n s e s when i n t r o m i t t i n g and e j a c u l a t i n g . T h e s e s t e r e o t y p e d r e s p o n s e s a r e a l s o e x h i b i t e d by m a s c u l i n i z e d g e n e t i c f e m a l e s a l t h o u g h t h e r e i s g e n e r a l l y no i n s e r t i o n or e m i s s i o n . Thus, i t d o e s n o t seem u n r e a s o n a b l e t o r e q u i r e a l l components o f male s e x u a l b e h a v i o u r t o be p r e s e n t b e f o r e t h e t e r m ' m a s c u l i n i z a t i o n ' i s u s e d , e s p e c i a l l y s i n c e t h e a b s e n c e o f i n t r o m i t t i n g and e j a c u l a t o r y b e h a v i o u r i n male r a t s i s v i e w e d a s e v i d e n c e f o r a b n o r m a l male s e x u a l b e h a v i o u r (Whalen, 1974). U n f o r t u n a t e l y , a l a r g e number of r e p o r t s on t h e e f f e c t s of n e o n a t a l c a s t r a t i o n and e a r l y a n d r o g e n t r e a t m e n t r e p o r t o n l y r e s u l t s o b t a i n e d f o r m o u n t i n g b e h a v i o u r ( e . g . , Edwards & B u r g e , 1971; Goy, B r i d s o n , & Young, 1964; Paup, C o n i g l i o , & C l emens, 1972; P h o e n i x e t a l . , 105 1959) a l t h o u g h t h e y o f t e n s t a t e t h a t t h e y r e c o r d e d o t h e r components o f male s e x u a l b e h a v i o u r ( e . g . , Edwards & B u r g e , 1971; P h o e n i x e t a l . , 1959). T h i s makes i t v e r y d i f f i c u l t t o draw any f i r m c o n c l u s i o n s on t h e m a s c u l i n i z i n g e f f e c t s of v a r i o u s t r e a t m e n t s and r a i s e s t h e p o s s i b i l i t y t h a t many o f t h e p r o c e d u r e s r e p o r t e d t o i n d u c e m a s c u l i n i z a t i o n do n o t . They may, however, i n d u c e p a r t i a l m a s c u l i n i z a t i o n . T h e r e i s one a d d i t i o n a l p r o b l e m f r e q u e n t l y e n c o u n t e r e d i n t h e l i t e r a t u r e w h i c h a l s o b e a r s d i r e c t l y on t h e p r e s e n t p a p e r . Some r e s e a r c h e r s ( e . g . , Edwards & B u r g e , 1971; N u c c i & B e a c h , 1971) have a p p a r e n t l y f a i l e d t o c o n s i d e r t h e p o s s i b i l i t y t h a t t h e l a c k o f an e f f e c t ( o r t h e n a t u r e of an e f f e c t ) c o u l d be due e n t i r e l y t o t h e f a c t t h a t t h e i r t r e a t m e n t s d i d n o t c o i n c i d e w i t h any o r a l l o f t h e a p p r o p r i a t e s e n s i t i v e p e r i o d . Many e r r o n e o u s c o n c l u s i o n s o c c u r i n t h e l i t e r a t u r e b e c a u s e of an a p p a r e n t f a i l u r e t o c o n s i d e r t h i s p o s s i b i l i t y . F o r example, Edwards & Burge (1971) c o n c l u d e d t h a t t h e r e i s " l i t t l e r e l i a b l e e v i d e n c e i n our d a t a t o i n d i c a t e n e o n a t a l a n d r o g e n i c s t i m u l a t i o n f a c i l i t a t e s a d u l t e x p r e s s i o n o f m a s c u l i n e s e x u a l b e h a v i o r . " . T h i s i s d e s p i t e t h e f a c t t h a t t h e y u s e d o n l y one dose o f TP (100 ^ g j a d m i n i s t e r e d o n l y on Day 1 a f t e r b i r t h . More p r o l o n g e d t r e a t m e n t a n d / o r a l a r g e r d o s e may have p r o d u c e d d i f f e r e n t e f f e c t s . The f i n d i n g s o f N u c c i & Beach (1971) may have had more s i g n i f i c a n t c o n s e q u e n c e s on t h e l i t e r a t u r e . N u c c i & Beach (1971) f o u n d t h a t p r e n a t a l TP t r e a t m e n t i n t h e h a m s t e r had no e f f e c t on any a s p e c t o f s e x u a l b e h a v i o u r o r p h y s i o l o g y i n a d u l t h o o d . S i n c e t h a t t i m e , l i t t l e , i f any, work has been 1 06 p u b l i s h e d on t h e e f f e c t s o f p r e n a t a l TP on s e x u a l d e v e l o p m e n t i n t h e h a m s t e r . T h i s s u g g e s t s t h a t s u b s e q u e n t r e s e a r c h e r s have assumed t h a t N u c c i & B e a c h ' s (1971) r e s u l t s p r e c l u d e t h e p o s s i b i l i t y t h a t p r e n a t a l TP may e x e r t an e f f e c t when f o l l o w e d by p o s t n a t a l t r e a t m e n t . T h i s i s a d a n g e r o u s c o n c l u s i o n f o r s e v e r a l r e a s o n s . F i r s t , N u c c i & Beach (1971) u s e d o n l y one d ose of TP whereas d i f f e r e n t d o s e s might have p r o d u c e d d i f f e r e n t e f f e c t s . S e c o n d , t h e d o s e employed by N u c c i & B e a c h (1971) was q u i t e h i g h (2 mg/day f o r t h r e e d a y s ) . T h a t i t was e i t h e r d e t r i m e n t a l t o t h e p r e g n a n t f e m a l e s , t h e pups, o r b o t h i s i n d i c a t e d by t h e f a c t t h a t a l t h o u g h 18 p r e g n a n t f e m a l e s were g i v e n TP, o n l y 18 pups s u r v i v e d t o t e s t i n g (an a v e r a g e of one p e r l i t t e r ) . I t i s n o t c l e a r whether t h e low number o f s u b j e c t s was a r e s u l t of s p o n t a n e o u s a b o r t i o n o r pup m o r t a l i t y , but e i t h e r i s i n d i c a t i v e o f a d e t r i m e n t a l (and p r o b a b l y s t r e s s f u l ) s i t u a t i o n . T hus, one b e g i n s t o wonder what made t h e s u r v i v i n g pups t h e e x c e p t i o n t o t h e r u l e and whether t h i s may have a f f e c t e d t h e i r b e h a v i o u r . T h i r d , a l t h o u g h N u c c i & Beach (1971) a d m i n i s t e r e d i n j e c t i o n s o v e r e i t h e r Days 11-13, 12-14, o r 13-15 of g e s t a t i o n , t h e y do n o t i n d i c a t e t h e number o f pups s u r v i v i n g under e a c h c o n d i t i o n . A l t h o u g h t h e y do s t a t e t h a t t h e r e were no d i f f e r e n c e s between pups i n d i f f e r e n t c o n d i t i o n s , i t i s p o s s i b l e t h a t t h e m a j o r i t y of s u r v i v o r s were from a g r o u p i n w h i c h p r e n a t a l t r e a t m e n t s d i d n o t e x e r t any e f f e c t . F i n a l l y , t h e f a i l u r e o f p r e n a t a l TP t r e a t m e n t t o e x e r t e f f e c t s on s e x u a l b e h a v i o u r does not p r e c l u d e t h e p o s s i b i l i t y t h a t i t i s a p r e r e q u i s i t e f o r t h e m a s c u l i n i z i n g a c t i o n o f p o s t n a t a l TP. F o r example, p r e n a t a l TP m i g h t e x e r t a p r i m i n g o r o r g a n i z i n g e f f e c t 107 on n e u r a l t i s s u e s t h a t i s e s s e n t i a l i f p o s t n a t a l TP i s t o e x e r t i t s f u l l e f f e c t . P r e n a t a l e x p o s u r e might e x e r t no v i s i b l e b e h a v i o u r a l o r p h y s i o l o g i c a l e f f e c t s , y e t t h e a b s e n c e of p e r i n a t a l a n d r o g e n e x p o s u r e c o u l d p r e c l u d e t h e f u l l d e v e l o p m e n t of o t h e r b e h a v i o u r s i n f l u e n c e d by a n d r o g e n s . Thus, i t would seem unwise t o c o n c l u d e t h a t p r e n a t a l a n d r o g e n t r e a t m e n t s e x e r t no e f f e c t on a d u l t s e x u a l b e h a v i o u r i n t h e h a m s t e r s o l e l y on t h e b a s i s o f t h e r e s u l t s o b t a i n e d by N u c c i & Beach ( 1 9 7 1 ) . F o r t u n a t e l y , t h e r e does seem t o be a t r e n d i n t h e r e c e n t l i t e r a t u r e t o c a r e f u l l y c o n s i d e r t h e p o s s i b i l i t y t h a t t h e e f f e c t s o b s e r v e d may r e f l e c t t h e n a t u r e of t h e t r e a t m e n t a s w e l l a s t h e p r o c e s s o f s e x u a l d i f f e r e n t i a t i o n . The e f f e c t s o f e a r l y h o r m o n a l e n v i r o n m e n t on a d u l t s e x u a l b e h a v i o u r have most f r e q u e n t l y been examined f o l l o w i n g t h e p e r i n a t a l a d m i n i s t r a t i o n of a n d r o g e n s t o f e m a l e s and f o l l o w i n g t h e n e o n a t a l c a s t r a t i o n of m a l e s . E x p e r i m e n t a l m a n i p u l a t i o n s s u c h a s t h e s e have i n d i c a t e d t h a t , i n a l l l a b o r a t o r y r o d e n t s s t u d i e d t o d a t e , t h e p r e s e n c e o f a n d r o g e n s d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n a l t e r s a d u l t s e x u a l b e h a v i o u r i n a manner t h a t v a r i e s w i t h d o s e , i n t e r v a l o f s t e r o i d a d m i n i s t r a t i o n r e l a t i v e t o p a r t u r i t i o n , and d u r a t i o n o f t r e a m e n t ( C a r t e r & L a n d a u e r , 1975; C o n i g l i o & C lemens, 1976; Edwards, 1971; G e r a l l & Ward, 1966; Goy e t a l . , 1964; N a d l e r , 1969; Paup e t a l . , 1972; P h o e n i x e t a l . , 1959). The d o s e , i n t e r v a l and d u r a t i o n d e p e n d e n t e f f e c t s o f p e r i n t a l a n d r o g e n t r e a t m e n t on f e m a l e s e x u a l b e h a v i o u r i n a d u l t h o o d a r e f a i r l y c l e a r and u n c o m p l i c a t e d . In t h e two l a b o r a t o r y r o d e n t s p e c i e s w i t h a l t r i c i a l young (no f u r , e y e s and 108 e a r s c l o s e d a t b i r t h , not v e r y m o t i l e ) and m ales t h a t a r e n a t u r a l l y d e f e m i n i z e d ( r a t and mouse), t h e a d m i n i s t r a t i o n of 100 ;ug t o 500 ^ug TP w i t h i n 48 hr o f b i r t h i s s u f f i c i e n t t o d e f e m i n i z e t h e a n i m a l (Clemens, S h r y n e , & G o r s k i , 1970; Edwards & B u r g e , 1971). T h i s t r e a t m e n t d o e s n o t n e c e s s a r i l y f u l l y m a s c u l i n i z e t h e a n i m a l , i n d i c a t i n g t h a t d e f e m i n i z a t i o n i s n o t d e p e n d e n t upon m a s c u l i n i z a t i o n . I t i s a l s o p o s s i b l e t o p r o d u c e b e h a v i o u r a l m a s c u l i n i z a t i o n w i t h o u t p r o d u c i n g p h y s i o l o g i c a l m a s c u l i n i z a t i o n (as d e t e r m i n e d by a n o g e n i t a l d i s t a n c e ) . F o r example, Ward (1969) f o u n d t h a t f e m a l e r a t s g i v e n TP e v e r y o t h e r day f r o m b i r t h t o Day 40 d i d not d i f f e r from n o r m a l f e m a l e s w i t h r e s p e c t t o a n o g e n i t a l d i s t a n c e a l t h o u g h t h e y d i d e x h i b i t a l l t h r e e components of male s e x u a l b e h a v i o u r a t l e v e l s c o m p a r a b l e t o , n o r m a l m a l e s . Thus, t h e p e r i o d o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n and t h e p e r i o d o f b e h a v i o u r a l m a s c u l i n i z a t i o n do n o t n e c e s s a r i l y c o i n c i d e . The h a m s t e r a l s o g i v e s b i r t h t o a l t r i c i a l young but m a l e s a r e n o t n a t u r a l l y d e f e m i n i z e d (Baum, 1979; Goldman, 1978; T i e f e r & J o h n s o n , 1975). In t h i s s p e c i e s , t h e a d m i n i s t r a t i o n o f a s i n g l e i n j e c t i o n of 100 pq t o 500 pq TP does n o t d e f e m i n i z e t h e f e m a l e h a m s t e r a l t h o u g h i t d o e s p r o d u c e l e v e l s o f s e x u a l r e c e p t i v i t i y s i m i l a r t o t h o s e o b s e r v e d i n t h e male ( A l l e v a , A l l e v a , & Umberger, 1969; J o h n s o n , 1975; Paup e t a l . , 1972). The g u i n e a p i g d i f f e r s f r o m t h e r a t , mouse and h a m s t e r i n t h a t i t g i v e s b i r t h t o more p r e c o c i a l young ( f u r p r e s e n t , e y e s and e a r s open, m o t i l e a t b i r t h ) . F o r TP a d m i n i s t r a t i o n t o e x e r t any major e f f e c t s i n t h i s s p e c i e s , i t must be g i v e n p r e n a t a l l y , v i a m a t e r n a l i n j e c t i o n s , i n d i c a t i n g t h a t f u l l d i f f e r e n t i a t i o n 109 o c c u r s b e f o r e b i r t h (Goy e t a l . , 1964; P h o e n i x e t a l . , 1959). To i n s u r e t h e s e n s i t i v e p e r i o d f o r d e f e m i n i z a t i o n i s n o t m i s s e d , r e s e a r c h e r s ( e . g . , Goy e t a l . , 1964; Goy, P h o e n i x , & M e i d i n g e r , 1967; P h o e n i x e t a l . , 1959) g e n e r a l l y employ a r e p e a t e d i n j e c t i o n p r o c e d u r e o v e r d i f f e r e n t p e r i o d s of g e s t a t i o n . T h i s makes i t d i f f i c u l t t o d e t e r m i n e i f a s i n g l e i n j e c t i o n o f TP a t t h e a p p r o p r i a t e t i m e would d e f e m i n i z e t h e f e m a l e g u i n e a p i g . In a d d i t i o n , t h e a c t u a l amount o f TP r e a c h i n g t h e pups c a n n o t be d e t e r m i n e d . I t i s c l e a r , however, t h a t t h e a d m i n i s t r a t i o n o f TP from Day 30-55 o f g e s t a t i o n ( w h i c h i s a b o u t 68 d a y s i n l e n g t h ) p r o d u c e s a permanent and s e v e r e d e f i c i t i n f e m a l e r e c e p t i v i t y (Goy e t a l . , 1964; Goy e t a l . , 1967). In f e m a l e s w h i c h c a n be d e f e m i n i z e d by a s i n g l e i n j e c t i o n o f TP a r o u n d t h e t i m e of b i r t h ( i . e . , t h e r a t and mouse), t h e e x a c t e f f e c t s o f TP on s e x u a l r e c e p t i v i t y i n a d u l t h o o d depend on t h e d o s e o f TP a d m i n i s t e r e d . The h i g h e r t h e d o s e , t h e l o w e r t h e r e c e p t i v i t y ( G e r a l l & Kenny, 1970; Goy e t a l . , 1964; W h i t s e t t & V a n d e n b e r g h , 1975). B e h a v i o u r a l s t u d i e s i n d i c a t e t h a t t h e d e c r e a s e d r e c e p t i v i t y c a u s e d by p e r i n a t a l TP i s due t o r e d u c e d r e s p o n d i n g t o EB and t o EB g i v e n i n c o n j u n c t i o n w i t h P (Clemens e t a l . , 1970; Edwards & Thompson, 1970; G e r a l l & Kenny, 1970; Goy e t a l . , 1967; Whalen e t a l . , 1971). F u r t h e r m o r e , i t now a p p e a r s t h a t t h e d e c r e a s e d r e s p o n s i v e n e s s t o EB i s due, a t l e a s t i n p a r t , t o a p e r i n a t a l a n d r o g e n - i n d u c e d d e c r e a s e i n t h e r a t e e s t r a d i o l r e c e p t o r s a r e r e p l e n i s h e d ( C i d l o w s k i & Muldoon, 1976). T h u s , t h e d o s e - d e p e n d e n t e f f e c t s of p e r i n a t a l a n d r o g e n s on f e m a l e r e c e p t i v i t y i n a d u l t h o o d may r e f l e c t d o s e - d e p e n d e n t e f f e c t s on t h e r e p l e n i s h m e n t of e s t r o g e n - b i n d i n g p r o t e i n s . 1 10 The d o s e , i n t e r v a l , and d u r a t i o n e f f e c t s o f p e r i n a t a l TP on t h e m a s c u l i n i z a t i o n of b e h a v i o u r a r e more complex t h a n t h e e f f e c t s on d e f e m i n i z a t i o n . B e c a u s e t h e r e a r e s e v e r a l components t o male s e x u a l b e h a v i o u r , i t i s p o s s i b l e t h a t p e r i n a t a l a n d r o g e n t r e a t m e n t c o u l d i n d u c e some o r a l l components o f male s e x u a l b e h a v i o u r . U n f o r t u n a t e l y , few r e s e a r c h e r s have been a m b i t i o u s enough t o c a r e f u l l y i n v e s t i g a t e t h e r e l a t i v e i m p o r t a n c e o f d o s e , d u r a t i o n , and i n t e r v a l of TP a d m i n i s t r a t i o n on t h e m a s c u l i n i z a t i o n o f s e x u a l b e h a v i o u r . Most o f t e n , two f a c t o r s ( i . e . , d o s e , t r e a t m e n t i n t e r v a l ) a r e h e l d c o n s t a n t w h i l e t h e t h i r d ( i . e . , d u r a t i o n ) i s v a r i e d . T h i s c a n make i t d i f f i c u l t , i f n o t i m p o s s i b l e , t o d e t e r m i n e t h e r e l a t i v e i m p o r t a n c e o f a l l f a c t o r s . F o r example, i f v a r y i n g t h e d u r a t i o n o f t r e a t m e n t e x e r t e d o n l y a s l i g h t b e h a v i o u r a l e f f e c t , i t c o u l d be t h a t t h e dose was t o o low, t h e i n t e r v a l was i n c o r r e c t , o r t h e d u r a t i o n t o o s h o r t ( o r some c o m b i n a t i o n ) . A l t h o u g h t h e r e a r e few e x p e r i m e n t s t h a t use s i m i l a r d o s e s , i n t e r v a l s , o r d u r a t i o n s , c o m p a r i s o n s between e x p e r i m e n t s do sh e d some l i g h t on t h e i m p o r t a n c e of v a r i o u s f a c t o r s . I t a p p e a r s t h a t i n t e r v a l and d u r a t i o n a r e more i m p o r t a n t f a c t o r s t h a n dose i n r o d e n t s p e c i e s s t u d i e d so f a r . F o r example, Ward (1969) f o u n d t h a t , i n f e m a l e r a t s , e i t h e r p r e n a t a l p l u s p o s t n a t a l o r p o s t n a t a l TP t r e a t m e n t l e d t o e j a c u l a t o r y r e s p o n s e s w h i l e p r e n a t a l TP t r e a t m e n t d i d n o t , i n d i c a t i n g t h a t p o s t n a t a l TP t r e a t m e n t i s e s s e n t i a l f o r t h e e j a c u l a t o r y r e s p o n s e i n t h e r a t . Goy e t a l . (1964) f o u n d t h a t f e m a l e g u i n e a p i g s r e c e i v i n g a t o t a l o f 50 mg TP o v e r d a y s 15-40 of g e s t a t i o n gave b i r t h t o young w h i c h e x h i b i t e d s i g n i f i c a n t l y l e s s m o u n t i n g b e h a v i o u r t h a n t h e young o f f e m a l e s g i v e n t h e same 111 amount of TP o v e r Days 30-55 o f g e s t a t i o n . In t h e h a m s t e r , t h e r e l a t i v e i m p o r t a n c e of t h e d o s e , i n t e r v a l , and d u r a t i o n of TP a d m i n i s t r a t i o n f o r m a s c u l i n i z a t i o n i s l e s s c l e a r . N u c c i & Beach (1971) f o u n d t h a t p r e n a t a l TP t r e a t m e n t i n t h e hamster d i d not i n c r e a s e any a s p e c t o f male s e x u a l b e h a v i o u r , s u g g e s t i n g t h a t m a s c u l i n i z a t i o n m ight t a k e p l a c e p o s t n a t a l l y o r a t l e a s t r e q u i r e s p o s t n a t a l a n d r o g e n e x p o s u r e . C o n i g l i o & Clemens (1976) f o u n d t h a t t h e a d m i n i s t r a t i o n o f 40 ^ug o r lOO^ug TP t o f e m a l e h a m s t e r s from b i r t h t o Day 5 l e d t o a g r e a t e r d e g r e e of m a s c u l i n i z a t i o n t h a n t r e a t m e n t from Day 6-10. However, no e j a c u l a t i o n s were o b s e r v e d i n any of t h e TP t r e a t e d f e m a l e s . T i e f e r & J o h n s o n (1975) f o u n d t h a t t h e a d m i n i s t r a t i o n o f 10 jug TP from b i r t h t o Day 20 a l s o p r o d u c e d mounts and i n t r o m i s s i o n s a l t h o u g h , a g a i n , no e j a c u l a t o r y b e h a v i o u r was o b s e r v e d . T h i s s u g g e s t s t h a t p e r h a p s p r e - and p o s t n a t a l TP t r e a t m e n t i s r e q u i r e d t o e l i c i t t h e e j a c u l a t o r y r e s p o n s e i n t h e h a m s t e r . To summarize, i n f e m a l e r a t s and mice a s i n g l e n e o n a t a l i n j e c t i o n o f TP w i l l d e c r e a s e l o r d o s i s r e s p o n d i n g i n a d o s e -d e p e n d e n t manner. The e f f e c t of n e o n a t a l TP on r e c e p t i v i t y i n t h e h a m s t e r d i f f e r s f r o m t h a t o b s e r v e d i n t h e r a t and mouse. A l t h o u g h TP d o e s d e c r e a s e f e m a l e s e x u a l r e s p o n d i n g i n t h e h a m s t e r , t h e e f f e c t i s n o t n e a r l y a s p r o n o u n c e d as t h a t o b s e r v e d i n o t h e r s p e c i e s . However, i t seems c l e a r t h a t , i n t h o s e s p e c i e s e xamined, a s i n g l e n e o n a t a l TP i n j e c t i o n c a n r e s u l t i n a l e v e l o f r e c e p t i v i t y s i m i l a r t o t h a t o b s e r v e d i n t h e male o f t h a t s p e c i e s ( A l l e v a e t a l . , 1969; Clemens e t a l . , 1970; Edwards & B u r g e , 1971). Note t h a t t h i s does not n e c e s s a r i l y i n d i c a t e 1 1 2 t h a t t h e f e m a l e i s d e f e m i n i z e d . The s e x u a l b e h a v i o u r o f t h e f e m a l e h a m s t e r i s m a s c u l i n i z e d by a s i n g l e n e o n a t a l TP i n j e c t i o n b u t t h e f e m a l e , l i k e t h e male, r e m a i n s c a p a b l e of d i s p l a y i n g f e m a l e s e x u a l b e h a v i o u r i n a d u l t h o o d ( A l l e v a e t a l . , 1969; J o h n s o n , 1975). In c o n t r a s t , a l l components o f male s e x u a l b e h a v i o u r can not be i n d u c e d by a s i n g l e n e o n a t a l TP i n j e c t i o n s (Edwards & B u r g e , 1971; Paup e t a l . , 1972). R a t h e r , m u l t i p l e i n j e c t i o n s o v e r t h e a p p r o p r i a t e i n t e r v a l a p p e a r t o be r e q u i r e d f o r f u l l b e h a v i o u r a l m a s c u l i n i z a t i o n ( C o n i g l i o & Clemens, 1976; Goy e t a l . , 1964; Ward, 1969). A s i d e from t h e e f f e c t s o f p e r i n a t a l a n d r o g e n on r e p r o d u c t i v e b e h a v i o u r and p h y s i o l o g y , e f f e c t s a r e o b s e r v e d i n o t h e r h o r m o n a l l y m e d i a t e d b e h a v i o u r s as w e l l . TP a d m i n i s t r a t i o n d u r i n g d i f f e r e n t i a t i o n p r o d u c e s m a s c u l i n e f o o d i n t a k e and body w e i g h t p a t t e r n s i n a d u l t f e m a l e r a t s , g u i n e a p i g s , and h a m s t e r s ( s e e Wade, 1976, f o r a r e v i e w ) . In a d d i t i o n , n e o n a t a l c a s t r a t i o n o f male r a t s and h a m s t e r s p r o d u c e s a f o o d i n t a k e and body w e i g h t p a t t e r n i n a d u l t h o o d w h i c h r e s e m b l e s t h a t o b s e r v e d i n t h e f e m a l e of t h e s p e c i e s . P e r i n a t a l TP a l s o a l t e r s a g g r e s s i v e b e h a v i o u r i n m i c e (Goldman, 1978) a n d s c e n t m a r k i n g b e h a v i o u r i n g e r b i l s ( T u r n e r , 1975). B o t h o f t h e s e b e h a v i o u r s a r e i n f l u e n c e d by sex hormones i n a d u l t h o o d , w i t h gonadectomy d e c r e a s i n g b e h a v i o u r and sex s t e r o i d r e p l a c e m e n t t h e r a p y r e s t o r i n g b e h a v i o u r t o p r e s u r g i c a l l e v e l s ( B r a i n , 1977; Y a h r , 1981). T h e r e i s now s u b s t a n t i a l e v i d e n c e t h a t p e r i n a t a l a n d r o g e n s m o d i f y n e u r a l c o n n e c t i o n s i n v a r i o u s a r e a s o f t h e b r a i n i n t h e r a t , mouse, and hamster ( D o r n e r & S t a u d t , 1968, 1969; F i e l d & 1 1 3 Raisman, 1976; G r e e n o u g h e t a l . , 1978; K o l a t a , 1979; Loy & M i l n e r , 1980; Raisman & F i e l d , 1976; T o r a n - A l l e r a n d , 1976). T h i s i n d i c a t e s t h a t t h e e f f e c t s o f p e r i n a t a l a n d r o g e n s go b eyond t h e s i m p l e a l t e r a t i o n of s t e r o i d b i n d i n g c a p a c i t y and r e p l e n i s h m e n t of r e c e p t o r s and i n t o t h e more complex r e a l m o f n e u r o c y t o l o g i c a l m o d i f i c a t i o n s . T h u s , t h e b e h a v i o u r a l a l t e r a t i o n s o b s e r v e d w i t h i n a s p e c i e s a f t e r p e r i n a t a l a n d r o g e n e x p o s u r e p r o b a b l y r e f l e c t b o t h c h a n g e s i n n e u r a l s t r u c t u r e and a l t e r a t i o n s i n r e c e p t o r r e p l e n i s h m e n t and a b i l i t y o f n e u r o n s t o b i n d v a r i o u s hormones. G i v e n t h e c a p a c i t y of p e r i n a t a l a n d r o g e n s t o a l t e r a v a r i e t y o f h o r m o n a l l y m e d i a t e d b e h a v i o u r s w i t h i n a s p e c i e s o f r o d e n t , i t seems p l a u s i b l e t h a t i n t e r s p e c i f i c d i f f e r e n c e s i n t h e o r g a n i z a t i o n a l e f f e c t s of p e r i n a t a l a n d r o g e n s may be r e s p o n s i b l e f o r some o f t h e i n t e r s p e c i f i c d i f f e r e n c e s o b s e r v e d i n h o r m o n a l l y m e d i a t e d b e h a v i o u r s . The o r g a n i z a t i o n a l e f f e c t o f p e r i n a t a l a n d r o g e n s c o u l d d i f f e r between s p e c i e s i n t h e e f f e c t s on n e u r a l s y n a p s e s , s t e r o i d b i n d i n g c a p a c i t y , r e c e p t o r r e p l e n i s h m e n t , o r some c o m b i n a t i o n o f t h e s e f a c t o r s . I f s o , one m i g h t e x p e c t t o f i n d t h i s d i f f e r e n c e t o be r e f l e c t e d by s e v e r a l h o r m o n a l l y m e d i a t e d b e h a v i o u r s s i n c e t h e o r g a n i z i n g e f f e c t s o f p e r i n a t a l a n d r o g e n s a r e not c o n f i n e d t o s e x u a l b e h a v i o u r . We have a l r e a d y seen t h a t r a t s , m i c e and g u i n e a p i g s a r e m a s c u l i n i z e d and d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s (Edwards & B u r g e , 1971; P h o e n i x e t a l . , 1959; S l o b e t a l . , 1973; Ward, 1969) w h i l e t h e h a m s t e r i s m a s c u l i n i z a e d but n o t d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s ( T i e f e r & J o h n s o n , 1971, 1975; Goldman, 1978). I t has a l s o been n o t e d e a r l i e r t h a t t h e h a m s t e r i s t h e o n l y r o d e n t 1 1 4 s t u d i e d so f a r i n w h i c h t h e f e m a l e e a t s and w e i g hs more t h a n t h e male ( K o w a l e w s k i , 1969, Wade, 1976). F u r t h e r m o r e , t h e h a m s t e r i s t h e o n l y known r o d e n t where t h e f e m a l e d i s p l a y s more a g g r e s s i o n t h a n t h e male ( H a r t , 1974; Moyer, 1974). Thus, we f i n d t h a t t h e h o r m o n a l r e g u l a t i o n o f a v a r i e t y o f h o r m o n a l l y m e d i a t e d b e h a v i o u r s i n t h e h a m s t e r d i f f e r s f r o m o t h e r l a b o r a t o r y r o d e n t s . Between s p e c i e s d i f f e r e n c e s i n t h e o r g a n i z i n g e f f e c t s of p e r i n a t a l a n d r o g e n on t h e n e u r a l s u b s t r a t e s r e g u l a t i n g t h e s e b e h a v i o u r s p r o v i d e s one e x p l a n a t i o n o f t h e s e d i f f e r e n c e s ( a l t h o u g h i t i s n o t n e c e s s a r i l y t h e o n l y e x p l a n a t i o n ) . R e g a r d l e s s of t h e r e a s o n f o r t h e d i f f e r e n c e between h a m s t e r s and o t h e r l a b o r a t o r y r o d e n t s , t h e d i f f e r e n c e s i n t h e e f f e c t s of p e r i n a t a l a n d r o g e n on s e x u a l b e h a v i o u r and t h e d i f f e r e n c e i n t h e h o r m o n a l r e g u l a t i o n of f o o d i n t a k e and body w e i g h t i n a d u l t h o o d s u g g e s t t h a t i t i s a t l e a s t p o s s i b l e t h a t t h e e x t e n t o f d e f e m i n i z a t i o n by a n d r o g e n s may d e t e r m i n e w h i c h sex s t e r o i d w i l l p r o d u c e t h e g r e a t e s t a l t e r a t i o n s i n f o o d i n t a k e and body w e i g h t i n a d u l t h o o d . R o d e n t s n o t d e f e m i n i z e d by p h y s i o l o g i c a l l e v e l s of a n d r o g e n s d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n may be most i n f l u e n c e d by a n d r o g e n s w h i l e r o d e n t s t h a t a r e d e f e m i n i z e d by a n d r o g e n s w o u l d r e s p o n d more t o o v a r i a n s t e r o i d s . T hus, t h e g e r b i l , b e i n g most r e s p o n s i v e t o o v a r i a n s t e o i d s i n r e g a r d s t o f o o d i n t a k e and body w e i g h t r e g u l a t i o n s h o u l d , l i k e t h e r a t , mouse, and g u i n e a p i g , be d e f e m i n i z e d by t h e p r e s e n c e o f p e r i n a t a l a n d r o g e n s . The o b j e c t i v e s of t h e r e s e a r c h i n t h i s s e c t i o n a r e t o : (1) d e t e r m i n e t h e e f f e c t s o f p e r i n a t a l a n d r o g e n s on a d u l t s e x u a l b e h a v i o u r and (2) e v a l u a t e t h e p r e s e n t h y p o t h e s i s t h a t knowledge 1 15 of t h e e x t e n t of p e r i n a t a l a n d r o g e n - i n d u c e d d e f e m i n i z a t i o n a l l o w s t h e p r e d i c t i o n o f w h i c h g o n a d a l s t e r o i d s w i l l e x e r t t h e p r i m a r y i n f l u e n c e on f o o d i n t a k e and body w e i g h t i n a d u l t h o o d (and v i c e v e r s a ) . GENERAL METHODS Mated p a i r s of g e r b i l s were o b t a i n e d f r o m Tumblebrook Farms. A l l had g i v e n b i r t h t o a t l e a s t one, but no more t h a n two, l i t t e r s . Upon p a r t u r i t i o n , a n i m a l s were s u p p l i e d w i t h two 27 cm x 23.5 cm p a p e r t o w e l s t o use as n e s t i n g m a t e r i a l . F r e s h b e d d i n g m a t e r i a l l e a d s t o h e i g h t e n e d d i g g i n g a c t i v i t y w h i c h may t e m p o r a r i l y d i s r u p t pup c a r e ( p e r s o n a l o b s e r v a t i o n ) . T h e r e f o r e , no c a g e s were c h a n g e d u n t i l t h e pups were a t l e a s t 20 d a y s o f age, when t h e i r e y e s open and m o t i l i t y i s g r e a t l y i n c r e a s e d . E x p e r i m e n t a l a n i m a l s were weaned a t a p p r o x i m a t e l y 30 d a y s of age and h o u s e d w i t h l i t t e r m a t e s u n t i l a b o u t 55 d a y s o f age when t h e y were t h e n s e p a r a t e d i n t o same sex p a i r s . At t h i s t i m e , a l l TP t r e a t e d m a l e s were removed. B e g i n n i n g a t a p p r o x i m a t e l y 90 d a y s o f age, a n i m a l s r e c e i v e d f i v e t e s t s f o r male s e x u a l b e h a v i o u r , w i t h t e s t s o c c u r r i n g e v e r y o t h e r day. S t i m u l u s f e m a l e s were b r o u g h t i n t o maximal r e c e p t i v i t y by t h e a d m i n i s t r a t i o n o f 10 j j g EB 48 and 24 h r b e f o r e t e s t i n g p l u s an i n j e c t i o n o f 500 jag P 3-5 h r p r i o r t o t e s t i n g . Mounts w i t h p e l v i c t h r u s t i n g , i n t r o m i s s i o n s (mounts w i t h t h r u s t i n g and p e n e t r a t i o n ) , and e j a c u l a t i o n s were r e c o r d e d u s i n g an E s t e r l i n e -Angus e v e n t r e c o r d e r . T h i s method o f r e c o r d i n g a l s o a l l o w s t h e d e t e r m i n a t i o n of t e m p o r a l p a r a m e t e r s d u r i n g t e s t i n g . I m m e d i a t e l y a f t e r t h e f i n a l t e s t f o r male s e x u a l b e h a v i o u r i n 1 16 i n t a c t a n i m a l s , a l l s u b j e c t s were g o n a d e c t o m i z e d w h i l e under a n e s t h e s i a g r a d e e t h e r . A f t e r r e c o v e r y , d a i l y i n j e c t i o n s of 10^ug EB were i n i t i a t e d w i t h t e s t s f o r f e m a l e s e x u a l b e h a v i o u r b e g i n n i n g on Day 6 of EB t r e a t m e n t . T e s t i n g c o n t i n u e d d a i l y t h r o u g h Day 13 o f EB t r e a t m e n t w i t h a f i n a l t e s t on t h e f o l l o w i n g day w h i c h o c c u r r e d 3-4 h r a f t e r t h e a d m i n i s t r a t i o n of 500^ug P. A f t e r a p e r i o d of no hormone t r e a t m e n t , a l l o w i n g d i s s i p a t i o n o f r e s i d u a l hormones, d a i l y i n j e c t i o n s of 100 jjq TP were i n i t i a t e d and c o n t i n u e d u n t i l t h e t e r m i n a t i o n of t h e e x p e r i m e n t . T e s t s o f male s e x u a l b e h a v i o u r o c c u r r e d on Days 15, 22, 29, and 36 o f TP t r e a t m e n t . Upon t e r m i n a t i o n of t e s t i n g , a n i m a l s were w e i g h e d , a n o g e n i t a l d i s t a n c e s r e c o r d e d and s c e n t g l a n d s m e asured ( l e n g t h and w i d t h ) . L i g h t i n g c y c l e s , g e n e r a l m a i n t e n a n c e , and f e m a l e s e x u a l t e s t i n g were a s d e s c r i b e d p r e v i o u s l y . EXPERIMENT 11 The e n d o c r i n e g l a n d s a r e n o t f u n c t i o n a l t h r o u g h o u t t h e e n t i r e d e v e l o p m e n t a l p e r i o d . T h u s , t h e p e r i o d i n w h i c h p e r i n a t a l a n d r o g e n s i n f l u e n c e s e x u a l d i f f e r e n t i a t i o n may be m i s s e d i f exogenous s t e r o i d s a r e a d m i n i s t e r e d a t a t i m e d i f f e r e n t f r o m t h e endogenous i n c r e a s e i n s t e r o i d s e c r e t i o n s (Goy, 1970). In a d d i t i o n , t h e i n f l u e n c e o f p e r i n a t a l a n d r o g e n s on s e x u a l d e v e l o p m e n t depends upon t h e l e v e l o f c i r c u l a t i n g a n d r o g e n s d u r i n g d i f f e r e n t i a t i o n ( G o r s k i , 1971, 1979). Thus, e i t h e r a low d o s e of TP o r t h e a d m i n i s t r a t i o n o f TP d u r i n g o n l y a p o r t i o n o f t h e p e r i o d of d i f f e r e n t i a t i o n c a n p r o d u c e d e g r e e s o f b e h a v i o u r a l m a s c u l i n i z a t i o n and b e h a v i o u r a l d e f e m i n i z a t i o n . 1 1 7 F u r t h e r m o r e , t h e s e n s i t i v e p e r i o d s f o r p h y s i o l o g i c a l m a s c u l i n i z a t i o n , b e h a v i o u r a l m a s c u l i n i z a t i o n , and b e h a v i o u r a l d e f e m i n i z a t i o n do not n e c e s s a r i l y c o i n c i d e . However, i t does a p p e a r t o be t h e c a s e t h a t , i n r o d e n t s w i t h a l t r i c i a l young ( h a m s t e r , r a t , and mouse), t h e p e r i o d o f s u s c e p t i b i l i t y t o a n d r o g e n - i n d u c e d d e f e m i n i z a t i o n o c c u r s a r o u n d t h e t i m e of b i r t h ( F e d e r & Wade, 1974; G o r s k i , 1979; Goy, 1970). I t was p r e v i o u s l y h y p o t h e s i z e d t h a t t h e e x t e n t o f a n d r o g e n -i n d u c e d d e f e m i n i z a t i o n c a n be u s e d t o p r e d i c t w h i c h sex s t e r o i d i s t h e p r i m a r y r e g u l a t o r of f o o d i n t a k e and body w e i g h t i n a g i v e n s p e c i e s of r o d e n t (and v i c e v e r s a ) . L i t t l e i s known a b o u t t h e e f f e c t s o f p e r i n a t a l a n d r o g e n s on s e x u a l b e h a v i o u r i n t h e g e r b i l . However, t h e f i n d i n g t h a t male g e r b i l s do not e x h i b i t f e m a l e , s e x u a l b e h a v i o u r d u r i n g c h r o n i c EB t r e a t m e n t ( E x p e r i m e n t 10) s u g g e s t s t h a t t h e male g e r b i l i s d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s . T h e r e r e m a i n s t h e p o s s i b i l i t y t h a t t h e f e m a l e g e r b i l i s not f u l l y d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s . F u r t h e r m o r e , a l t h o u g h t h e r a t and mouse c a n be d e f e m i n i z e d by a s i n g l e n e o n a t a l i n j e c t i o n o f 100 t o 500^ug TP, t h i s i s not n e c e s s a r i l y t h e c a s e i n t h e f e m a l e g e r b i l . However, g e r b i l s , l i k e r a t s , m i c e , and h a m s t e r s , have a s h o r t g e s t a t i o n p e r i o d and g i v e b i r t h t o a l t r i c i a l y oung. I t seems r e a s o n a b l e t o assume t h a t , i f t h e d i f f e r e n t i a t i o n p r o c e s s i s s i m i l a r t o t h a t o b s e r v e d i n t h e r a t and mouse, o r i n t h e h a m s t e r , a s i n g l e n e o n a t a l i n j e c t i o n of TP s h o u l d r e s u l t i n some d e g r e e o f d e f e m i n i z a t i o n i n t h e f e m a l e g e r b i l as w e l l . T h u s , a p a r a d i g m w h i c h would a l l o w c o m p a r i s o n s between s p e c i e s o f t h e e f f e c t s of a s i n g l e n e o n a t a l i n j e c t i o n of TP on f e m a l e s e x u a l b e h a v i o u r would be 1 18 b e n e f i c i a l . The p r e s e n t e x p e r i m e n t was d e s i g n e d t o d e t e r m i n e : (1) t h e e x t e n t o f n e o n a t a l T P - i n d u c e d d e f e m i n i z a t i o n i n t h e f e m a l e g e r b i l , (2) between s p e c i e s d i f f e r e n c e s i n t h e e f f e c t s of a s i n g l e n e o n a t a l TP i n j e c t i o n , and (3) i f t h e e f f e c t s o f n e o n a t a l TP a d m i n i s t r a t i o n on t h e e x h i b i t i o n of male and f e m a l e s e x u a l b e h a v i o u r i n a d u l t h o o d c a n be p r e d i c t e d on t h e b a s i s o f w h i c h sex s t e r o i d e x e r t s t h e g r e a t e s t i n f l u e n c e on a d u l t f o o d i n t a k e and body w e i g h t r e g u l a t i o n . B a s e d on t h e r e s u l t s of E x p e r i m e n t s 9 and 10 p l u s t h e r e s u l t s o f Maass & Wade ( 1 9 7 7 ) , t h e p r e s e n t h y p o t h e s i s p r e d i c t s t h a t t h e p r e s e n c e o f a n d r o g e n s d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n w i l l d e f e m i n i z e male and f e m a l e g e r b i l s . Method Pups r e c e i v e d a s i n g l e i n j e c t i o n o f e i t h e r 100 pq TP (low d o s e ) , 1 mg TP ( h i g h d o s e ) , o r t h e v e h i c l e (0.01 c c p e a n u t o i l ) w i t h i n 24 h r of b i r t h . B e c a u s e t h e s k i n of newborn g e r b i l s does no t r e a d i l y c l o s e a f t e r n e e d l e p u n c t u r e , a s m a l l amount of C o l l o d i o n ( F i s h e r S c i e n t i f i c ) was a p p l i e d t o t h e p u n c t u r e t o p r e v e n t l e a k a g e . In a d d i t i o n , s u c c e s s of t h e i n j e c t i o n was v e r i f i e d by e x a m i n a t i o n o f t h e i n j e c t i o n s i t e f o r a s l i g h t but d i s t i n c t b u l g e under t h e s k i n w h i c h i s c r e a t e d by t h e f l u i d . I m m e d i a t e l y a f t e r i n j e c t i o n , pups were r e t u r n e d t o t h e home c a g e . A t o t a l o f f o u r g r o u p s was c r e a t e d , v e h i c l e t r e a t e d f e m a l e s ( V F ) , v e h i c l e t r e a t e d m a l e s (VM), 100 ^ ug TP t r e a t e d f e m a l e s ( L T P ) , and 1 mg TP t r e a t e d f e m a l e s ( H T P ) . The f i n a l n's a t t h e t i m e o f t e s t i n g were 21, 15, 19, and 14 f o r t h e VM, VF, LTP and HTP g r o u p s , r e s p e c t i v e l y . 1 19 R e s u l t s and D i s c u s s i o n An e x a m i n a t i o n o f t h e s e x u a l b e h a v i o u r d a t a i n d i c a t e d t h a t none of t h e g r o u p s d u r i n g i n t a c t t e s t i n g f o r male b e h a v i o u r e x h i b i t e d even m o d e r a t e l e v e l s o f b e h a v i o u r a l m a s c u l i n i z a t i o n ( T a b l e 3 ) . T h i s was e x p e c t e d f o r t h e f e m a l e s u b j e c t s s i n c e t h e y l a c k a s i g n i f i c a n t s o u r c e of endogenous a n d r o g e n s . However, t h e r e l a t i v e l a c k o f male s e x u a l b e h a v i o u r i n male c o n t r o l s i s somewhat p u z z l i n g . The r e l a t i v e l a c k o f male s e x u a l a c t i v i t y was a l s o e v i d e n t d u r i n g t h e gonadectomy p l u s TP t e s t i n g , a l t h o u g h VM a n i m a l s d i d a p p e a r t o e x h i b i t somewhat g r e a t e r s e x u a l a c t i v i t y ( T a b l e 4, 4 a ) . The d a t a f o r t h e f e m a l e s e x u a l b e h a v i o u r t e s t s s u g g e s t e d t h a t o n l y t h e VF a n i m a l s e x h i b i t e d an a p p r e c i a b l e l e v e l of r e c e p t i v i t y ( T a b l e 5 ) . No a n a l y s e s were p e r f o r m e d on t h e male s e x u a l b e h a v i o u r d a t a s i n c e a l l g r o u p s e x h i b i t e d a v e r y low l e v e l of a c t i v i t y . The d a t a do s u g g e s t t h a t n e i t h e r t h e 100 pq nor t h e 1 mg dose o f TP were a d e q u a t e t o p r o d u c e t h e f u l l complement of male s e x u a l b e h a v i o u r , and t h u s were n o t s u f f i c i e n t t o f u l l y b e h a v i o u r a l l y m a s c u l i n i z e t h e a n i m a l s . However, t h e e x a c t n a t u r e o f t h e m a s c u l i n i z i n g a c t i o n o f TP i s d i f f i c u l t t o a s s e s s s i n c e t h e c o n t r o l a n i m a l s a l s o e x h i b i t e d f a i r l y low l e v e l s of male s e x u a l b e h a v i o u r . A 4x8 ( g r o u p by t e s t day) r e p e a t e d measures a n a l y s i s of v a r i a n c e w i t h a n e s t e d f a c t o r was p e r f o r m e d on t h e f e m a l e s e x u a l b e h a v i o u r d a t a and r e v e a l e d a s i g n i f i c a n t e f f e c t o f g r o u p , F (3,66) = 7 . 7 7 , p = 0.0002. A s u b s e q u e n t Newman-Keul's a n a l y s i s on t h i s e f f e c t i n d i c a t e d t h a t , o v e r a l l , VF a n i m a l s were s i g n i f i c a n t l y more r e c e p t i v e t h a n LTP, HTP, and VM a n i m a l s . O t h e r s i g n i f i c a n t e f f e c t s were t e s t , F ( 7 , 4 4 1 ) = 2.86, p = 0.006, T a b l e 3. M a l e s e x u a l b e h a v i o u r i n i n t a c t male g e r b i l s and i n f e m a l e g e r b i l s t r e a t e d n e o n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e . PERCENT RESPONDING SEXUAL RESPONSE VM HTP LTP VF (n=21) (n=14) (n=l9) (n=15) M 4.8 0.0 0.0 0.0 T1 I 4.8 0.0 0.0 0.0 E 0.0 0.0 0.0 0.0 M 4.8 0.0 5.3 0.0 T2 I 4.8 0.0 0.0 0.0 E 4.8 0.0 0.0 0.0 M 9.5 0.0 5.3 0.0 T3 I 0.0 0.0 0.0 0.0 • E 0.0 0.0 0.0 0.0 M 4.8 14.3 5.3 0.0 T4 I 4.8 0.0 5.3 0.0 E 4.8 0.0 0.0 0.0 M 10.0 0.0 5.3 0.0 T5 I 4.8 0.0 0.0 0.0 E 4.8 0.0 0.0 0.0 VF = v e h i c l e i n j e c t e d f e m a l e s , LTP = 100 jiq t e s t o s t e r o n e p r o p i o n a t e (TP) i n j e c t i o n s , HTP = 1 mg TP i n j e c t i o n , VM = v e h i c l e i n j e c t e d m a l e s . M = mounts, I = i n t r o m i s s i o n s , E = e j a c u l a t i o n s . T1-5 = c o n s e c u t i v e t e s t s e v e r y 2 d a y s . T a b l e 4. Ma l e s e x u a l b e h a v i o u r i n c a s t r a t e d male g e r b i l s and i n o v a r i e c t o m i z e d f e m a l e g e r b i l s t r e a t e d n e o n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e . PERCENT RESPONDING SEXUAL RESPONSE VM HTP LTP VF (n=21) (n=14) (n=l9) (n=15) M 0.0 0 .0 0 .0 0 .0 T1 I 0.0 0 .0 0 .0 0 .0 E 0.0 0 .0 0 .0 0 .0 M 4.8 0.0 0 .0 0 .0 T2 I 4.8 0.0 0 .0 0 .0 E 0.0 0 .0 0 .0 0 .0 M 9.5 7. 1 0.0 0 .0 T3 I 4.8 7.1 0.0 0 .0 E 0.0 0 .0 0 .0 0 .0 M 76.2 7.1 15.3 0.0 T4 I 33.3 7.1 0.0 0 .0 E 23.8 0.0 0 .0 0 .0 VF = v e h i c l e i n j e c t e d f e m a l e s , LTP = 100 jug t e s t o s t e r o n e p r o p i o n a t e (TP) i n j e c t i o n , HTP 1 mg TP i n j e c t i o n , VM = v e h i c l e i n j e c t e d m a l e s . M = mounts, I = i n t r o m i s s i o n s , E = e j a c u l a t i o n s . T1-4 = c o n s e c u t i v e w e e k l y t e s t s . 1 22 T a b l e 4a. A d d i t i o n a l measures of s e x u a l b e h a v i o u r f o r T4 d a t a o f T a b l e 4*. MEASURE n _ VM X ±SE _ H T P n X ±SE n LTP X ±SE ML ( s e c ) 1 6 1057.6 210.0 1 1076.0 000.0 3 1028.7 497.7 I L ( s e c ) 8 877.4 144.3 1 1561.0 000.0 - -E L ( s e c ) 5 565.4 1 54.3 - - - -P E I ( s e c ) 4 234.5 30.8 - - - -E J ( f r e q ) 5 1 .4 0.2 - - - -* A n i m a l s t h a t d i d not e x h i b i t male s e x u a l a c t i v i t y were e x c l u d e d f r o m t h e t a b l e . VM = v e h i c l e i n j e c t e d m a l e s , HTP = f e m a l e s i n j e c t e d w i t h 1 mg t e s t o s t e r o n e p r o p i o n a t e (TP) w i t h i n 24 h r o f b i r t h , LTP = f e m a l e s i n j e c t e d w i t h 100 jug TP w i t h i n 24 h r o f b i r t h . ML = mount l a t e n c y , I L = i n t r o m i s s i o n l a t e n c y , EL = e j a c u l a t i o n l a t e n c y , PEI = p o s t - e j a c u l a t o r y i n t e r v a l , t h e t i m e i n t e r v a l between t h e f i r s t i n t r o m i s s s i o n and e j a c u l a t i o n , E J = mean number o f e j a c u l a t i o n s . 123 T a b l e 5. Female s e x u a l b e h a v i o u r i n c a s t r a t e d male g e r b i l s and i n o v a r i e c t o m i z e d f e m a l e g e r b i l s t r e a t e d n e o n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e and a d m i n i s t e r e d o v a r i a n s t e r o i d s i n a d u l t h o o d . TEST (EB) GRC )UP VF X ±SE LTF X ±SE HTF X ±SE VM X ±SE T1 2.7 2.7 0.0 0.0 0.0 0.0 0.0 0.0 T2 4.0 4.0 0.0 0.0 0.0 0.0 0.0 0.0 T3 10.0 6.8 0.0 0.0 0.0 0.0 0.0 0.0 T4 4.7 4.7 0.0 0.0 0.0 0.0 0.0 0.0 T5 11.3 7.2 5.3 5.3 0.0 0.0 0.0 0.0 T6 25.3 11.3 0.0 0.0 0.0 0.0 0.0 0.0 T7 34.0 12.2 0.0 0.0 0.0 0.0 0.0 0.0 T8 26.7 10.7 0.0 0.0 0.0 0.0 0.0 0.0 (EB+P) T9 86.6 7.1 2.1 1 .6 0.0 0.0 2.9 2.9 V F = v e h i c l e i n j e c t e d f e m a l e s , LTP = 100 jug t e s t o s t e r o n e p r o p i o n a t e (TP) i n j e c t i o n ^ HTP = 1 mg TP i n j e c t i o n , VM = v e h i c l e i n j e c t e d male. X = mean s e x u a l r e c e p t i v i t y , number o f l o r d o s i s p o s t u r e s e x h i b i t e d by t h e f e m a l e d i v i d e d by t h e number o f male mounts w i t h p e l v i c t h r u s t i n g and m u l t i p l i e d by 100. A n i m a l s r e c e i v e d 13 c o n s e c u t i v e i n j e c t i o n s o f 10 jag e s t r a d i o l b e n z o a t e (EB) and were t e s t e d on Days 6-13. On Day 14, 100 jag p r o g e s t e r o n e (P) was a d m i n i s t e r e d 3-4 h r p r i o r t o t e s t i n g . 124 and g r o u p by t e s t , F ( 2 1 , 4 4 ) = 3.43, 2 < 0 . 0 0 0 1 . Thus, b o t h t h e 100 ug and t h e 1 mg TP d o s e s d e f e m i n i z e d t h e f e m a l e g e r b i l . In a d d i t i o n , male g e r b i l s a p p e a r e d t o be d e f e m i n i z e d by endogenous a n d r o g e n s d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n . An e x a m i n a t i o n o f t h e d a t a f o r t h e p h y s i o l o g i c a l m easures ( s c e n t g l a n d l e n g t h and w i d t h , body w e i g h t , and a n o g e n i t a l d i s t a n c e ) s u g g e s t e d t h a t some d e g r e e o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n had o c c u r r e d and t h a t , f o r a l l m e a s u r e s , t h e d e g r e e o f m a s c u l i n i z a t i o n was r e l a t e d t o t h e dose o f TP a d m i n i s t e r e d a t b i r t h ( F i g u r e 1 3 a - d ) . S e p a r a t e one-way a n a l y s e s o f v a r i a n c e were p e r f o r m e d on t h e d a t a f o r e a c h of t h e p h y s i o l o g i c a l m e a sures and r e v e a l e d s i g n i f i c a n t g r o u p d i f f e r e n c e s , beyond t h e 0.0001 l e v e l , f o r body w e i g h t , F (3,62) = 9.28, s c e n t g l a n d l e n g t h , F ( 3 , 6 2 ) = 64.80, s c e n t g l a n d w i d t h , F ( 3 , 6 2 ) = 30.38, and a n o g e n i t a l d i s t a n c e F (3,62) = 620.66. Newman-Keul's a n a l y s e s , w i t h c*- s e t a t 0.05 i n d i c a t e d t h a t , f o r body w e i g h t , g r o u p s VF and LTP d i d not d i f f e r and t h a t g r o u p s HTP and VM d i d n o t d i f f e r b u t t h a t a n i m a l s i n g r o u p s VF and LTP w e i g h e d s i g n i f i c a n t l y l e s s t h a n a n i m a l s i n g r o u p s HTP and VM. The s c e n t g l a n d l e n g t h o f VF and LTP a n i m a l s was a l s o f o u n d t o be s i m i l a r w h i l e s c e n t g l a n d l e n g t h o f HTP a n i m a l s was g r e a t e r t h a n f o r VF and LTP a n i m a l s and l e s s t h a n f o r VM a n i m a l s . F o r b o t h s c e n t g l a n d w i d t h and a n o g e n i t a l d i s t a n c e , VF a n i m a l m e asures were s i g n i f i c a n t l y l o w e r t h a n LTP w h i c h were s i g n i f i c a n t l y l o w e r t h a n HTP, w h i c h were s i g n i f i c a n t l y l o w e r t h a n VM m e a s u r e s . Thus, b o t h s c e n t g l a n d w i d t h and a n o g e n i t a l d i s t a n c e a p p e a r t o be q u i t e s e n s i t i v e t o t h e e f f e c t s of e a r l y a n d r o g e n s . 1 25 F i g u r e 13. C o m p a r i s o n of i n d i c e s of p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n male g e r b i l s and i n f e m a l e g e r b i l s r e c e i v i n g a s i n g l e n e o n a t a l i n j e c t i o n of t e s t o s t e r o n e p r o p i o n a t e . M e a s u r e s o f s c e n t g l a n d l e n g t h ( a ) , s c e n t g l a n d w i d t h ( b ) , body w e i g h t ( c ) , and a n o g e n i t a l d i s t a n c e (d) were t a k e n a f t e r 36 days of t r e a t m e n t w i t h 100 pq t e s t o s t e r o n e p r o p i o n a t e ( T P ) . W i t h i n 24 hr of b i r t h , f e m a l e s r e c e i v e d a s i n g l e i n j e c t i o n of t h e o i l v e h i c l e ( V F ) , 100^ug TP ( L T P ) , o r 1 mg TP (HTP) w h i l e m a l e s r e c e i v e d a s i n g l e i n j e c t i o n o f t h e v e h i c l e (VM). < TI I —I TJ < T| X H TJ Body Weight (g) cn Co o~) CD 0 KD ^ o) 00 o 1 • • • ' 1 o Anogenital Distance (mm) [so ^ co co o ro • • • J J < T l H TJ X —I TJ < Scent Gland Length (mm) _». K> N) ro ^ O) co g K> Scent Gland Width (mm) t4V TJ X H TJ < W 4^ Ul 0) ^ op } 1 27 The r e s u l t s of t h e p r e s e n t e x p e r i m e n t i n d i c a t e t h a t a s i n g l e i n j e c t i o n of TP a t b i r t h i s c a p a b l e o f d e f e m i n i z i n g t h e f e m a l e g e r b i l . However, t h e e f f e c t s o f a s i n g l e TP i n j e c t i o n on t h e d e v e l o p m e n t o f male s e x u a l b e h a v i o u r i s d i f f i c u l t t o a s s e s s s i n c e a l l a n i m a l s e x h i b i t e d low l e v e l s o f male s e x u a l a c t i v i t y . I t i s p o s s i b l e t h a t t h e low l e v e l s o f male c o p u l a t o r y b e h a v i o u r e x h i b i t e d by c o n t r o l m a l e s d u r i n g t h e i n t a c t t e s t i n g were due t o an e x t r a n e o u s v a r i a b l e ( i . e . , s t r e s s ) w h i c h i n d i r e c t l y r e s u l t e d i n d e c r e a s e d l e v e l s of endogenous a n d r o g e n s . A l a r g e d e c r e a s e i n endogenous a n d r o g e n s c o u l d r e s u l t i n d e c r e a s e d s e x u a l b e h a v i o u r . I f t h i s i s t h e c a s e , s e x u a l b e h a v i o u r d u r i n g TP a d m i n i s t r a t i o n s h o u l d have been g r e a t e r t h a n d u r i n g i n t a c t t e s t i n g b e c a u s e t h e l e v e l o f c i r c u l a t i n g a n d r o g e n s i s c o n t r o l l e d . . T h i s i s i n d e e d t h e c a s e ( s e e T a b l e s 3, 4 and 4a) a l t h o u g h t h e d i f f e r e n c e i s not as g r e a t as one m i g h t e x p e c t . The r e s u l t s f o r t e s t s of male s e x u a l a c t i v i t y d u r i n g TP a d m i n i s t r a t i o n a l s o s u g g e s t t h a t TP t r e a t e d f e m a l e s were not f u l l y m a s c u l i n i z e d by a s i n g l e n e o n a t a l TP i n j e c t i o n . On t h e f i n a l t e s t o f male s e x u a l a c t i v i t y d u r i n g TP t r e a t m e n t , 76% of VM a n i m a l s , v e r s u s 12% o f T P - t r e a t e d f e m a l e s e x h i b i t e d m o u n t i n g b e h a v i o u r . F u r t h e r m o r e , w h i l e 33% o f VM a n i m a l s e x h i b i t e d b e h a v i o u r a l i n t r o m i s s i o n , o n l y 3% o f T P - t r e a t e d f e m a l e s d i d s o . F i n a l l y , 24% o f VM a n i m a l s e j a c u l a t e d a t l e a s t once d u r i n g t h e f i n a l TP t e s t w h i l e none o f t h e T P - t r e a t e d f e m a l e s e x h i b i t e d t h e b e h a v i o u r a l e q u i v a l e n t of t h i s r e s p o n s e ( s e e T a b l e 4 ) . A l t h o u g h t h e r e s u l t s a r e not d e f i n i t i v e , t h e r e i s a s u g g e s t i o n t h a t t h e f e m a l e g e r b i l , l i k e o t h e r f e m a l e r o d e n t s , r e q u i r e s more t h a n a s i n g l e n e o n a t a l TP i n j e c t i o n f o r f u l l b e h a v i o u r a l 1 28 m a s c u l i n i z a t i o n t o o c c u r . N o t e , however, t h a t t h i s does not a p p e a r t o be t h e c a s e f o r d e f e m i n i z a t i o n , w h i c h does a p p e a r t o be a c h i e v e d by a s i n g l e n e o n a t a l i n j e c t i o n of TP. Thus, t h e e f f e c t s of n e o n a t a l a n d r o g e n t r e a t m e n t i n t h e g e r b i l on t h e d e v e l o p m e n t o f s e x u a l b e h a v i o u r i s , a t l e a s t i n some r e s p e c t s , s i m i l a r t o t h a t o b s e r v e d i n o t h e r r o d e n t s . B a s e d on t h e f o o d i n t a k e d a t a , t h e p r e d i c t i o n was made t h a t a n d r o g e n s d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n would d e f e m i n i z e t h e g e r b i l . The r e s u l t s o f t h e p r e s e n t e x p e r i m e n t s u p p o r t t h e p r e s e n t h y p o t h e s i s t h a t t h e e x t e n t o f d e f e m i n i z a t i o n d u r i n g s e x u a l d i f f e r e n t i a t i o n d e t e r m i n e s w h i c h sex s t e r o i d w i l l e x e r t t h e g r e a t e s t i n f l u e n c e on a d u l t f o o d i n t a k e and body w e i g h t . However, i t r e m a i n s t o be d e t e r m i n e d i f p e r i n a t a l a n d r o g e n s w i l l f u l l y m a s c u l i n i z e s e x u a l b e h a v i o u r i n t h e g e r b i l . EXPERIMENT 12 The r e s u l t s o f E x p e r i m e n t 11 i n d i c a t e t h a t some d e g r e e o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n a s w e l l a s b e h a v i o u r a l d e f e m i n i z a t i o n c a n be a c h i e v e d by a s i n g l e i n j e c t i o n o f 1 mg TP a d m i n i s t e r e d w i t h 24 h r o f b i r t h . F u r t h e r m o r e , i t would a p p e a r t h a t p h y s i o l o g i c a l m a s c u l i n i z a t i o n c a n o c c u r i n t h e a b s e n c e o f b e h a v i o u r a l m a s c u l i n i z a t i o n . However, f u l l b e h a v i o u r a l m a s c u l i n i z a t i o n d o e s n o t a p p e a r t o be a c h i e v e d by s u c h an i n j e c t i o n . In t h e f e m a l e h a m s t e r , p r e n a t a l a n d r o g e n a d m i n i s t r a t i o n a p p e a r s t o e x e r t no m a s c u l i n i z i n g e f f e c t on p h y s i o l o g i c a l m easures o r t h e c a p a c i t y t o d i s p l a y male s e x u a l b e h a v i o u r i n a d u l t h o o d ( N u c c i & Beach, 1971). P o s t n a t a l TP 129 a d m i n i s t r a t i o n does a l t e r t h e c a p a c i t y of t h e f e m a l e hamster t o e x h i b i t male s e x u a l a c t i v i t y i n a d u l t h o o d ( J o h n s o n , 1975; T i e f e r & J o h n s o n , 1975). The r a t , on t h e o t h e r hand, shows t h e g r e a t e s t d e g r e e of b e h a v i o u r a l m a s c u l i n i z a t i o n when g i v e n TP p r e - and p o s t n a t a l l y (Goy, 1970; G e r a l l & Ward, 1966; Ward, 1969). A l t h o u g h t h e m a s c u l i n i z i n g e f f e c t o f p e r i n a t a l a n d r o g e n s i s n o t a major i s s u e i n t h e h y p o t h e s i s b e i n g t e s t e d , i t i s o f i n t e r e s t t h a t n e o n a t a l TP may n o t l e a d t o a s i g n i f i c a n t i n c r e a s e i n m o u n t i n g b e h a v i o u r i n t h e f e m a l e g e r b i l . I t i s p o s s i b l e t h a t p r e n a t a l o r p r e - p l u s p o s t n a t a l TP t r e a t m e n t w i l l i n c r e a s e t h e e x t e n t of b e h a v i o u r a l m a s c u l i n i z a t i o n i n t h e g e r b i l . Thus, t h e p r e s e n t e x p e r i m e n t was d e s i g n e d t o d e t e r m i n e t h e e f f e c t s of p r e -p l u s p o s t n a t a l a n d r o g e n t r e a t m e n t on p h y s i o l o g i c a l and b e h a v i o u r a l m a s c u l i n i z a t i o n i n t h e f e m a l e g e r b i l . Method P r e g n a n t f e m a l e g e r b i l s were g i v e n i n j e c t i o n s of e i t h e r 100 ^ug o r 1 mg o f TP p e r day f o r a p p r o x i m a t e l y 6 d a y s p r i o r t o b i r t h . Pups r e c e i v e d i n j e c t i o n s of e i t h e r 100 jug TP o r o i l w i t h i n 24 h r of b i r t h . Thus, a t o t a l of f o u r g r o u p s was c r e a t e d , 100 jjg + o i l ( G 1 ) , 1 00 j j g + 1 00 ^ug ( G 2 ) , 1 mg + o i l ( G 4 ) , and 1 mg + 100 ^ug ( G 4 ) . A l l weaning, h o u s i n g , s u r g i c a l , i n j e c t i o n , and t e s t i n g p r o c e d u r e s were i d e n t i c a l t o t h o s e u s e d i n E x p e r i m e n t 11 w i t h one e x c e p t i o n . To i n s u r e t h a t l a c k o f male s e x u a l a c t i v i t y was not due t o t h e dose o f TP a d m i n i s t e r e d , lOO^ug TP t e s t s were f o l l o w e d by 4 (one p e r week) t e s t s o f male s e x u a l b e h a v i o u r w i t h a n i m a l s r e c e i v i n g 500 pq TP. P h y s i o l o g i c a l measures were t a k e n a f t e r t h e f i n a l 100 pq TP t e s t t o a l l o w c o m p a r i s o n w i t h t h e r e s u l t s o b t a i n e d i n E x p e r i m e n t 11. 1 30 O r i g i n a l l y , v e h i c l e c o n t r o l a n i m a l s from E x p e r i m e n t 11 were t o be t h e o n l y c o n t r o l a n i m a l s employed. However, t h e o b s e r v a t i o n o f low l e v e l s o f s e x u a l a c t i v i t y i n t h i s s t u d y a s w e l l as i n E x p e r i m e n t 11 s u g g e s t e d t h a t , a l t h o u g h u n l i k e l y , t h e r e may have been an e f f e c t o f i n j e c t i o n s t r e s s w h i c h was s u f f i c i e n t t o a l t e r b e h a v i o u r . Thus, an a d d i t i o n a l s e t of c o n t r o l a n i m a l s was t e s t e d t o d e t e r m i n e i f i n j e c t i o n s p e r se were i n f l u e n c i n g s e x u a l d e v e l o p m e n t . F o r c o n t r o l p u r p o s e s , p r e g n a n t f e m a l e s e i t h e r r e c e i v e d d a i l y i n j e c t i o n s of o i l f o r a p p r o x i m a t e l y t h e f i n a l 6 d a y s o f g e s t a t i o n o r t h e y r e c e i v e d no i n j e c t i o n s . I n a d d i t i o n , h a l f o f t h e pups i n e a c h o f t h e p r e n a t a l c o n d i t i o n s r e c e i v e d a s i n g l e i n j e c t i o n of o i l w i t h i n 24 h r of b i r t h w h i l e t h e r e m a i n d e r d i d n o t , r e s u l t i n g i n a t o t a l o f f o u r g r o u p s ( p r e n a t a l w i t h o r w i t h o u t i n j e c t i o n by p o s t n a t a l w i t h o r w i t h o u t i n j e c t i o n ) . R e s u l t s and D i s c u s s i o n None of t h e TP t r e a t e d a n i m a l s i n t h e p r e s e n t e x p e r i m e n t e x h i b i t e d male o r f e m a l e s e x u a l b e h a v i o u r , i n d i c a t i n g t h a t t h e y were i n d e e d b e h a v i o u r a l l y d e f e m i n i z e d a l t h o u g h t h e y a p p a r e n t l y were n o t b e h a v i o u r a l l y m a s c u l i n i z e d . A d d i t i o n a l c o n t r o l a n i m a l s d i d , however, d i s p l a y male and f e m a l e s e x u a l b e h a v i o u r . R e s u l t s o b t a i n e d f o r t h e a d d i t i o n a l c o n t r o l a n i m a l s i n d i c a t e d t h a t n e i t h e r p r e - , p o s t - , nor p r e - p l u s p o s t n a t a l i n j e c t i o n s p e r se p r o d u c e d a d e c l i n e i n t h e s e x u a l a c t i v i t y of i n t a c t m a l e s . As i n E x p e r i m e n t 11, t h e l e v e l o f male s e x u a l a c t i v i t y was r a t h e r low but i t d i d n o t a p p e a r t o d i f f e r between g r o u p s ( T a b l e 6). However, some d i f f e r e n c e s d i d become a p p a r e n t d u r i n g t h e TP t e s t i n g . D a t a p r e s e n t e d i n T a b l e s 7 and 7a T a b l e 6. Mal e s e x u a l b e h a v i o u r i n i n t a c t male g e r b i l s e x p o s e d t o v e h i c l e i n j e c t i o n s p e r i n a t a l l y . SEXUAL RESPONSE I 3ERCENT RE ZS POND ING G1 (n=12) G2 (n=11 ) G3 (n=12) G4 (n=14) M T1 I E 8.3 8.3 0.0 9.1 9.1 9. 1 0.0 0 .0 0 .0 14.1 7.1 0.0 M T2 I E 8.3 0.0 0 .0 9. 1 9.1 9.1 0.0 0 .0 0 .0 14.3 14.3 0.0 M T3 I E 8.3 8.3 8.3 9.1 0.0 0 .0 8.3 0.0 0 .0 21 .4 14.3 14.3 M T4 I E 25 . 0 8.3 8.3 9.1 9.1 9. 1 0.0 0 .0 0 .0 7.1 7.1 7.1 M T5 I E 25 . 0 16.7 8.3 9.1 9.1 9.1 8.3 8.3 8.3 21.4 14.3 7.1 P r e n a t a l v e h i c l e i n j e c t i o n s were a c h i e v e d by i n j e c t i n g one h a l f of t h e g e r b i l s d u r i n g t h e l a s t 6 d a y s o f p r e g n a n c y w i t h t h e v e h i c l e . P o s t n a t a l a d m i n i s t r a t i o n c o n s i s t e d of i n j e c t i n g one h a l f o f t h e pups i n e a c h p r e n a t a l c o n d i t i o n w i t h i n 24 h r of b i r t h . G1 = no p r e - o r n e o n a t a l t r e a t m e n t , G2 = n e o n a t a l t r e a t m e n t o n l y , G3 = p r e n a t a l t r e a t m e n t o n l y , G4 = p r e - and n e o n a t a l t r e a t m e n t . M = mounts, I = i n t r o m i s s i o n , E = e j a c u l a t i o n s . T1-5 = c o n s e c u t i v e t e s t s e v e r y 2 d a y s . 1 32 i n d i c a t e t h a t m a l e s e x p o s e d t o v e h i c l e i n j e c t i o n s p r e - and p o s t n a t a l l y e x h i b i t e d , more s e x u a l a c t i v i t y w h i l e r e c e i v i n g TP t h a n w h i l e i n t a c t . T h i s s u g g e s t s t h a t p e r i n a t a l i n j e c t i o n s may p r o d u c e a l t e r a t i o n s i n s t e r o i d s e n s i t i v i t i e s . The f i n d i n g t h a t a l l f e m a l e s e x h i b i t e d e q u i v a l e n t and n o r m a l s e x u a l r e c e p t i v i t y when g i v e n c h r o n i c EB and EB p l u s P ( T a b l e 8 ) , suggest.s t h a t any a l t e r a t i o n s i n s t e r o i d s e n s i t i v i t i e s may be r e s t r i c t e d t o a n d r o g e n s . T h e r e i s a p h y s i o l o g i c a l i n d i c a t i o n t h a t p e r i n a t a l i n j e c t i o n s may have been s t r e s s f u l . T e s t i c u l a r w e i g h t s were r e c o r d e d a t t h e t i m e o f gonadectomy and were f o u n d t o be l o w e r , a l t h o u g h n o t s i g n i f i c a n t l y l o w e r , i n a l l a n i m a l s e x p o s e d t o p r e -a n d / o r p o s t n a t a l i n j e c t i o n s . T h i s s u g g e s t s t h a t l e v e l s o f endogenous a n d r o g e n s may have been r e d u c e d i n t h e s e a n i m a l s . The o b s e r v a t i o n t h a t TP a d m i n i s t r a t i o n d i d i n c r e a s e s e x u a l a c t i v i t y i n a n i m a l s g i v e n t h e v e h i c l e p r e - and p o s t n a t a l l y i s c o n s i s t e n t w i t h t h i s i d e a . However, t h e f a i l u r e t o o b s e r v e i n t e r g r o u p d i f f e r e n c e s i n male s e x u a l a c t i v i t y d u r i n g i n t a c t t e s t i n g s u g g e s t s t h a t , u n l e s s t h e r e was a n o t h e r f a c t o r o p e r a t i n g t o r e d u c e s e x u a l a c t i v i t y i n a d u l t h o o d , t h e a l t e r a t i o n i n t e s t e s w e i g h t was not s u f f i c i e n t t o r e s u l t i n b e h a v i o u r a l c h a n g e . T h e r e i s a t l e a s t one e x p l a n a t i o n o f t h e s e a p p a r e n t l y c o n t r a d i c t o r y r e s u l t s . I t i s p o s s i b l e t h a t p e r i n a t a l i n j e c t i o n s a c t u a l l y i n c r e a s e d t h e s e n s i t i v i t y o f t h e a n i m a l s t o a n d r o g e n s . I f an e x t r a n e o u s f a c t o r was o p e r a t i n g i n a d u l t h o o d t o r e d u c e a n d r o g e n l e v e l s and t h u s s e x u a l b e h a v i o u r , t h e e f f e c t m i ght n o t be a p p a r e n t b e c a u s e t h e l e v e l s o f s e x u a l r e s p o n d i n g i n a l l a n i m a l s would be l i m i t e d by t h e low a n d r o g e n l e v e l s . The T a b l e 7. M a l e s e x u a l b e h a v i o u r i n c a s t r a t e d male g e r b i l s e x p o s e d t o p e r i n a t a l v e h i c l e i n j e c t i o n s . PERCENT RESPONDING SEXUAL RESPONSE G1 G2 G3 G4 (n=l2) (n = 9) (n=12) (n=11) M 8.3 11.1 0.0 18.2 T1 I 0.0 11.1 0.0 18.2 E 0.0 11.1 0.0 9.2 M 16.7 22.2 0.0 63.6 T2 I 8.3 11.1 0.0 54.5 E 8.3 0.0 0 .0 45.5 M 16.7 11.1 0.0 45.5 T3 I 8.3 11.1 0.0 45.5 E 0.0 11.1 0.0 45.5 M 8.3 11.1 0.0 54.5 T4 I 8.3 11.1 0.0 54.5 E 8.3 11.1 0.0 54.5 P r e n a t a l a d m i n i s t r a t i o n was a c h i e v e d by i n j e c t i n g one h a l f o f t h e g e r b i l s w i t h t h e v e h i c l e ( o i l ) d u r i n g t h e l a s t 6 d a y s o f p r e g n a n c y . N e o n a t a l a d m i n i s t r a t i o n c o n s i s t e d o f i n j e c t i n g one h a l f o f t h e pups from e a c h o f t h e p r e n a t a l c o n d i t i o n s w i t h i n 24 h r of b i r t h . G1 = no p r e - o r n e o n a t a l i n j e c t i o n , G2 = n e o n a t a l i n j e c t i o n o n l y , G3 = p r e n a t a l i n j e c t i o n o n l y , G4 = p r e - and n e o n a t a l i n j e c t i o n . M = mounts, I = i n t r o m i s s i o n s , E = e j a c u l a t i o n s . T1-4 c o n s e c u t i v e w e e k l y t e s t s . 1 34 T a b l e 7a. A d d i t i o n a l measures o f s e x u a l b e h a v i o u r f o r T4 d a t a o f T a b l e 7*. MEASURE GI n X ±SE n G2 X ±SE n G4 X ±SE ML ( s e c ) 1 460.0 000.0 1 464.0 000.0 6 291 .7 67.3 I L ( s e c ) 1 468.0 000.0 - - - 6 318.2 64.2 E L ( s e c ) 1 577.7 000.0 - - - 6 577.7 79.7 P E I ( s e c ) 1 220.0 000.0 - - - 6 212.5 11.7 E J ( f r e q ) 1 3.0 0.0 - - - 6 3.0 0.7 * A n i m a l s t h a t d i d n o t e x h i b i t male s e x u a l a c t i v i t y were e x c l u d e d f r o m t h e t a b l e . P r e n a t a l a d m i n i s t r a t i o n was a c h i e v e d by i n j e c t i n g one h a l f o f t h e g e r b i l s w i t h t h e v e h i c l e ( o i l ) d u r i n g t h e l a s t 6 d a y s of p r e g n a n c y . N e o n a t a l a d m i n i s t r a t i o n c o n s i s t e d o f i n j e c t i n g one h a l f of t h e pups from e a c h p r e n a t a l c o n d i t i o n w i t h t h e v e h i c l e w i t h i n 24 h r o f b i r t h . G1 = no p r e - o r n e o n a t a l i n j e c t i o n , G2 = n e o n a t a l i n j e c t i o n o n l y , G4 = p r e -and n e o n a t a l i n j e c t i o n . ML = mount l a t e n c y , I L = i n t r o m i s s i o n l a t e n c y , EL = e j a c u l a t i o n l a t e n c y , PEI = p o s t -e j a c u l a t o r y i n t e r v a l , t h e t i m e i n t e r v a l between t h e f i r s t i n t r o m i s s s i o n and e j a c u l a t i o n , E J = mean number o f e j a c u l a t i o n s . 1 35 T a b l e 8. Female s e x u a l b e h a v i o u r i n o v a r i e c t o m i z e d f e m a l e g e r b i l s e x p o s e d t o p e r i n a t a l v e h i c l e i n j e c t i o n s . TEST (EB) GRC )UP G1 X ±SE _ G2 X ±SE _ G3 X ±SE G4 X ±SE T1 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 T2 0.0 0.0 0.0 0.0 5.6 5.6 0.0 0.0 T3 3.6 3.6 0.0 0.0 8.9 8.9 14.0 9.5 T4 23.6 12.6 0.0 0.0 17.8 12.2 0.0 0.0 T5 14.5 10.1 0.0 0.0 15.6 9.1 20.0 13.3 T6 12.7 8.5 0.0 0.0 17.8 9.1 19.0 12.7 T7 15.5 10.6 0.0 0.0 18.9 11.1 19.0 12.7 (EB+P) T9 74.5 11.8 72. 1 7.9 80.0 4.7 79.0 8.5 P r e n a t a l a d m i n i s t r a t i o n was a c h i e v e d by i n j e c t i n g one h a l f o f t h e g e r b i l s w i t h t h e v e h i c l e ( o i l ) d u r i n g t h e l a s t 6 d a y s o f p r e g n a n c y . N e o n a t a l a d m i n i s t r a t i o n c o n s i s t e d o f i n j e c t i n g one h a l f o f t h e pups from e a c h of t h e p r e n a t a l c o n d i t i o n s w i t h i n 24 h r of b i r t h . G1 = no p r e - o r n e o n a t a l i n j e c t i o n , G2 = n e o n a t a l i n j e c t i o n o n l y , G3 = p r e n a t a l i n j e c t i o n o n l y , G4 = p r e - and n e o n a t a l i n j e c t i o n . X = mean s e x u a l r e c e p t i v i t y , number o f l o r d o s i s p o s t u r e s e x h i b i t e d by t h e f e m a l e d i v i d e d by t h e number o f male mounts w i t h p e l v i c t h r u s t i n g and m u l t i p l i e d by 100. A n i m a l s r e c e i v e d 13 c o n s e c u t i v e i n j e c t i o n s o f 10 jjg e s t r a d i o l b e n z o a t e (EB) and were t e s t e d on Days 6-13. On Day 14, 100 j j g p r o g e s t e r o n e (P) was a d m i n i s t e r e d 3-4 h r p r i o r t o t e s t i n g . 136 a d m i n i s t r a t i o n of TP would i n c r e a s e a n d r o g e n l e v e l s and c o u l d remove t h e c e i l i n g e f f e c t due t o low a n d r o g e n l e v e l s . T h i s w ould a l l o w d i f f e r e n c e s t o be o b s e r v e d . I t s h o u l d be n o t e d t h a t , i n a n i m a l s r e c e i v i n g p e r i n a t a l TP, TP i t s e l f may have e x e r t e d e f f e c t s w h i c h c o u l d have been q u i t e d i f f e r e n t f r o m t h o s e o b s e r v e d i n v e h i c l e t r e a t e d a n i m a l s . The r e s u l t s f o r t h e p h y s i o l o g i c a l measures i n d i c a t e t h a t , as i n E x p e r i m e n t 11, some d e g r e e o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n o c c u r r e d i n a l l TP t r e a t e d a n i m a l s f o r a l l m e a s u r e s . In a d d i t i o n , i t a p p e a r e d t h a t p r e n a t a l e x p o s u r e t o 1 mg TP was more e f f e c t i v e i n i t s m a s c u l i n i z i n g e f f e c t s on s c e n t g l a n d l e n g t h and w i d t h and on a n o g e n i t a l d i s t a n c e t h a n was t h e 100 pq p r e n a t a l TP t r e a t m e n t ( F i g u r e 1 4 a - c ) . F u r t h e r m o r e , when c o m p a r i n g t h e means o f t h e s e measures f o r e a c h of t h e f o u r e x p e r i m e n t a l g r o u p s w i t h t h e means f o r t h e a d d i t i o n a l c o n t r o l a n i m a l s , i t a p p e a r s t h a t a n i m a l s i n a l l TP g r o u p s e x h i b i t a m a s c u l i n e t r e n d and, i n a d d i t i o n , G4 a n i m a l s a r e q u i t e s i m i l a r t o male c o n t r o l s on s e v e r a l m e a s u r e s ( T a b l e 9 ) . F i n a l l y , i t a l s o a p p e a r s t h a t p r e n a t a l e x p o s u r e t o v e h i c l e i n j e c t i o n s e x e r t e d some m a s c u l i n i z i n g e f f e c t s w h i l e n e o n a t a l e x p o s u r e d i d n o t . D a t a f o r t h e p h y s i o l o g i c a l measurements o f t h e TP t r e a t e d a n i m a l s were a n a l y z e d s e p a r a t e l y u s i n g a 2x2 a n a l y s i s of v a r i a n c e f o r n e s t e d f a c t o r s . A 2x2x2 ( g e n d e r , p r e n a t a l e x p o s u r e , p o s t n a t a l e x p o s u r e ) , n e s t e d f a c t o r a n a l y s i s of v a r i a n c e was u s e d t o a n a l y z e t h e a d d i t i o n a l c o n t r o l d a t a . A l l s u b s i d i a r y a n a l y s e s u s e d t h e Newman-Keul's p r o c e d u r e w i t h s e t a t 0.05. The a n a l y s e s of v a r i a n c e f o r TP t r e a t e d a n i m a l s 1 37 F i g u r e 14. C o m p a r i s o n o f i n d i c e s of p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n f e m a l e g e r b i l s t r e a t e d p e r i n a t a l l y w i t h t e s t o s t e r o n e p r o p i o n a t e . P r e n a t a l a d m i n i s t r a t i o n was a c h i e v e d by i n j e c t i n g g e r b i l s d u r i n g t h e l a s t 6 d a y s o f p r e g n a n c y w i t h e i t h e r 100 jug o r 1 mg t e s t o s t e r o n e p r o p i o n a t e ( T P ) . P o s t n a t a l a d m i n i s t r a t i o n c o n s i s t e d o f i n j e c t i n g pups w i t h i n 24 h r o f b i r t h w i t h e i t h e r t h e v e h i c l e or 100 jug TP. The e f f e c t s o f p r e n a t a l TP d o s e , i n d e p e n d e n t o f p o s t n a t a l t r e a t m e n t , a r e p r e s e n t e d i n p a n a l s a - c . The e f f e c t s o f p o s t n a t a l t r e a t m e n t , i n d e p e n d e n t o f p r e n a t a l TP d o s e , a r e p r e s e n t e d i n p a n e l d. 138 /g23 £ 22H g21" 0 ^ 2 0 -| 19-0 1 0 o CO 100jjg 1mg Prenatal TP Dose £ E \ ^ •g "D C O 8' 100jjg 1mg Prenatal TP Dose E E 0 O c 03 +-• CO Q "c 0 D) O c < lo-g-s' 7-6-5-1 100±jg 1mg Prenatal TP Dose ^10' E 0 g 8' CO | 7H Q c o c < Ojjg 100jjg Postnatal TP Dose 1 39 T a b l e 9. C o m p a r i s o n o f i n d i c e s o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n u n t r e a t e d male and f e m a l e g e r b i l s , male and f e m a l e g e r b i l s e x p o s e d t o v e h i c l e i n j e c t i o n s p e r i n a t a l l y , and f e m a l e g e r b i l s e x p o s e d t o t e s t o s t e r o n e p r o p i o n a t e p e r i n a t a l l y . TREATMENT GROUP SCENT GLAND LENGTH mm ±SE SCENT GLAND WIDTH mm ±SE BODY WEIGHT g ±SE ANOGENITAL DISTANCE mm ±SE VF 1 14. 45 0. 74 3. 36 0. 20 63. 1 6 2 .06 2. 18 0 . 1 2 VF2 15. 50 0. 52 3. 75 0. 16 59. 50 1 .34 2. 46 0 .17 VF3 16. 33 0. 53 4. 1 1 0. 26 61 . 80 1 .56 2. 33 0 .17 VF4 15. 67 0. 57 3. 80 0. 22 . 60. 49 1 . 1 1 2 40 0 .24 G1 18. 88 1 . 12 5. 1 3 0. 35 64. 38 1 .54 6 25 0 .77 G2 20 09 0 58 5. 46 0. 21 66. 77 0 .62 8 45 0 .36 G3 20 70 1 .27 5. 90 0 31 67. 10 1 .80 8 .50 0 .40 G4 22 40 0 .98 6. 20 0 29 64. 45 1 .60 9 .40 0 .40 VM1 23 .83 0 .49 6. 17 0 17 70 59 1 .44 1 1 .83 0 .27 VM2 24 .67 0 .55 6. 33 0 .17 63 .99 1 .63 1 1 .67 0 .50 VM3 26 .08 0 .48 6. 25 0 .18 70 .39 2 .03 1 2 .82 0 .48 VM4 25 .00 0 .51 6. 45 0 .28 69 .64 1 .64 12 .82 0 .48 P r e n a t a l t e s t o s t e r o n e p r o p i o n a t e (TP) a d m i n i s t r a t i o n was a c h i e v e d by i n j e c t i n g g e r b i l s d u r i n g t h e l a s t 6 days o f p r e g n a n c y w i t h e i t h e r l O O j j g o r 1 mg TP. P o s t n a t a l a d m i n i s t r a t i o n c o n s i s t e d o f i n j e c t i n g pups w i t h i n 24 hr of b i r t h w i t h e i t h e r t h e v e h i c l e o r l O O j a g TP. V e h i c l e a d m i n i s t r a t i o n f o l l o w e d a s i m i l a r p r o c e d u r e w i t h one h a l f o f t h e p r e g n a n t f e m a l e s r e c e i v i n g i n j e c t i o n s and one h a l f o f t h e pups from e a c h c o n d i t i o n r e c e i v i n g an i n j e c t i o n a t b i r t h . VF = v e h i c l e t r e a t e d f e m a l e s , VF1 = no p r e - o r n e o n a t a l v e h i c l e i n j e c t i o n , VF2 = n e o n a t a l v e h i c l e i n j e c t i o n o n l y , VF3 = p r e n a t a l v e h i c l e i n j e c t i o n o n l y , VF4 = p r e - and n e o n a t a l v e h i c l e i n j e c t i o n . G1 = 100 pq TP p r e n a t a l l y and o i l p o s t n a t a l l y , G2 = 100 pq TP p r e n a t a l l y and n e o n a t a l l y , G3 = 1 mg TP p r e n a t a l l y and o i l n e o n a t a l l y , G4 = 1 mg TP p r e n a t a l l y and 100 pq TP n e o n a t a l l y . VM1-4 t r e a t m e n t s were s i m i l a r t o t h e VF1-4 g r o u p s e x c e p t t h a t t h e s u b j e c t s were male. 1 40 i n d i c a t e d a s i g n i f i c a n t e f f e c t o f p r e n a t a l hormone d o s e (100 j j g v s 1 mg) f o r s c e n t g l a n d l e n g t h , F ( 1 , 3 5 ) = 3.92, p_ < 0.05, s c e n t g l a n d w i d t h , F ( 1 , 3 5 ) = 6.54, p_ = 0.01, and a n o g e n i t a l d i s t a n c e , F ( 1 , 3 5 ) = 8.74, 2 = 0.006. The s u b s i d i a r y a n a l y s e s i n d i c a t e d t h a t , f o r e a c h measure, t h e 1 mg dose o f TP l e d t o s i g n i f i c a n t l y h i g h e r s c o r e s t h a n t h e 100 ijg d o s e . P o s t n a t a l hormone e x p o s u r e ( o i l v s 100 ug) had a s i g n i f i c a n t e f f e c t on a n o g e n i t a l d i s t a n c e , F ( 1 , 3 5 ) = 8.46, 2 = 0.006, a l t h o u g h i t d i d n o t e x e r t a s i g n i f i c a n t e f f e c t on o t h e r m e a s u r e s . No e f f e c t s o f TP were f o u n d t o be s i g n i f i c a n t f o r body w e i g h t m e a s u r e s , p o s s i b l y b e c a u s e a l l f o u r g r o u p s e x h i b i t e d body w e i g h t s s i m i l a r t o t h o s e o b s e r v e d i n g r o u p VM a n i m a l s i n E x p e r i m e n t 11. The a n a l y s i s of v a r i a n c e p e r f o r m e d on t h e d a t a f r o m t h e a d d i t i o n a l c o n t r o l a n i m a l s i n d i c a t e d a s i g n i f i c a n t e f f e c t of p r e n a t a l t r e a t m e n t f o r s c e n t g l a n d l e n g t h , F ( 1 , 7 9 ) = 29.73, 2 < 0.0001, s c e n t g l a n d w i d t h , F ( 1 , 7 9 ) = 9.71, 2 = 0.0003, and a n o g e n i t a l d i s t a n c e , F ( 1 , 7 9 ) = 48.77, 2 < 0.0001. F u r t h e r a n a l y s i s of t h e s e e f f e c t s i n d i c a t e d t h a t , i n a l l c a s e s , a n i m a l s e x p o s e d t o p r e n a t a l v e h i c l e i n j e c t i o n s e x h i b i t e d g r e a t e r p h y s i o l o g i c a l measurements t h a n a n i m a l s not e x p o s e d t o p r e n a t a l i n j e c t i o n s , r e g a r d l e s s o f p o s t n a t a l t r e a t m e n t . In a d d i t i o n , a s i g n i f i c a n t g e n d e r by p r e n a t a l t r e a t m e n t by p o s t n a t a l t r e a t m e n t i n t e r a c t i o n was f o u n d f o r s c e n t g l a n d l e n g t h , F ( 1 , 7 9 ) = 4.46, 2 = 0.04, and s c e n t g l a n d w i d t h , F ( 1 , 7 9 ) = 4.42, 2 = 0.04. F u r t h e r a n a l y s i s o f t h e s e e f f e c t s i n d i c a t e d t h a t m a l e s r e c e i v i n g o n l y p r e n a t a l v e h i c l e i n j e c t i o n s had s i g n i f i c a n t l y g r e a t e r s c e n t g l a n d l e n g t h s t h a n o t h e r m a l e s . A l l males had s i g n i f i c a n t l y g r e a t e r s c e n t g l a n d l e n g t h s t h a n f e m a l e s . On t h e o t h e r hand, 141 s c e n t g l a n d w i d t h d i d n o t d i f f e r between males but f e m a l e s r e c e i v i n g any i n j e c t i o n e x p o s u r e had s i g n i f i c a n t l y g r e a t e r s c e n t g l a n d w i d t h s t h a n n o n - i n j e c t e d f e m a l e s . A l t h o u g h t h e s e r e s u l t s i n d i c a t e t h a t i n j e c t i o n s p e r se c a n e x e r t a m a s c u l i n i z i n g e f f e c t , an e x a m i n a t i o n of T a b l e 9 r e v e a l s t h a t a l l v e h i c l e i n j e c t e d f e a m l e s e x h i b i t e d p h y s i o l o g i c a l m easures below t h o s e o b s e r v e d i n TP t r e a t e d f e m a l e s . T h i s i n d i c a t e s t h a t a p e r i n a t a l i n j e c t i o n e f f e c t d i d n o t , i n i t s e l f , p r o d u c e t h e m a s c u l i n i z i n g e f f e c t o b s e r v e d i n TP t r e a t e d a n i m a l s , a l t h o u g h i t may have c o n t r i b u t e d t o i t . The r e s u l t s o f t h e p r e s e n t e x p e r i m e n t i n d i c a t e t h a t p r e -p l u s p o s t n a t a l TP t r e a t m e n t (G4) c a n l e a d t o h i g h l e v e l s o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n w i t h o u t n e c e s s a r i l y p r o d u c i n g b e h a v i o u r a l m a s c u l i n i z a t i o n . I t s h o u l d be n o t e d , however, t h a t t h e l a c k of male s e x u a l a c t i v i t y may be due t o a f a c t o r ( i . e . , s t r e s s ) t h a t i s n o t d i r e c t l y r e l a t e d t o t h e o r g a n i z i n g a c t i o n o f p e r i n a t a l a n d r o g e n s . P h y s i o l o g i c a l m a s c u l i n i z a t i o n a p p e a r s most i n f l u e n c e d by p r e n a t a l hormone e x p o s u r e , as i n d i c a t e d by g r e a t e r s c e n t g l a n d w i d t h , l e n g t h , and g r e a t e r a n o g e n i t a l d i s t a n c e s t h a n o b s e r v e d i n E x p e r i m e n t 11. F u r t h e r m o r e , as i n E x p e r i m e n t 11, d ose d e p e n d e n t e f f e c t s o f TP were o b s e r v e d on p h y s i o l o g i c a l m e a s u r e s . The p r e s e n t e x p e r i m e n t i n d i c a t e s t h e p r e s e n c e of p r e n a t a l TP i s g e n e r a l l y more i m p o r t a n t t h a n t h e p r e s e n c e o r a b s e n c e of TP on t h e day of b i r t h . However, i t i s not p o s s i b l e t o d e t e r m i n e whether t h i s e f f e c t i s due t o t h e t o t a l amount o f TP a d m i n i s t e r e d , t h e d u r a t i o n of hormone t r e a t m e n t , an i n c r e a s e d s e n s i t i v i t y t o TP d u r i n g p a r t o r a l l o f p r e n a t a l t r e a t m e n t , o r t o some c o m b i n a t i o n o f t h e s e f a c t o r s . 142 GENERAL DISCUSSION I t was o r i g i n a l l y p r e d i c t e d t h a t , b e c a u s e o v a r i a n s t e r o i d s a p p e a r t o be t h e p r i m a r y h o r m o n a l r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t i n t h e g e r b i l , t h e p r e s e n c e of a n d r o g e n s d u r i n g t h e p e r i o d o f s e x u a l d i f f e r e n t i a t i o n w ould d e f e m i n i z e t h e g e r b i l . The r e s u l t s o f E x p e r i m e n t 11 and 12 i n d i c a t e t h a t b o t h p r e - p l u s p o s t n a t a l and n e o n a t a l TP t r e a t m e n t do d e f e m i n i z e t h e g e r b i l , a r e s u l t c o n s i s t e n t w i t h t h e h y p o t h e s i s . T h e s e r e s u l t s a r e s i m i l a r t o t h o s e o b t a i n e d f o r t h e f e m a l e r a t and mouse w h i c h a r e a l s o d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s (Clemens e t a l . , 1970; Edwards & B u r g e , 1971; Edwards & Thompson, 1970; Whalen e t a l . , 1971) and a r e i n c o n t r a s t w i t h t h o s e o b t a i n e d f o r t h e f e m a l e h a m s t e r w h i c h i s not f u l l y d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s ( A l l e v a e t a l . , 1969; Paup e t a l . , 1972; T i e f e r & J o h n s o n , 1971, 1975). E x p e r i m e n t 11 f u r t h e r i n d i c a t e d t h a t 100 ^ g and 1 mg TP were e s s e n t i a l l y e q u a l i n t h e i r a b i l i t y t o d e f e m i n i z e t h e f e m a l e g e r b i l , s u g g e s t i n g t h a t i f d o s e - d e p e n d e n t e f f e c t s on l o r d o s i s b e h a v i o u r a r e t o be o b s e r v e d , l o w e r n e o n a t a l d o s e s o f TP must be e m p l o y e d . T h i s c o n t r a s t s w i t h r e s u l t s o b t a i n e d i n t h e r a t where 100 j j g o n l y p a r t i a l l y d e f e m i n i z e s b e h a v i o u r (mean LQ = 40, Clemens e t a l . , 1970). I t i s p o s s i b l e t h a t t h i s d i f f e r e n c e i s due t o t h e l e s s e r body w e i g h t and b l o o d volume o f t h e g e r b i l w h i c h c o u l d r e s u l t i n a h i g h e r c o n c e n t r a t i o n o f t e s t o s t e r o n e r e a c h i n g t h e b r a i n i n t h e g e r b i l . However, m i c e , w h i c h a r e s m a l l e r t h a n g e r b i l s , a l s o e x h i b i t some r e c e p t i v i t y a f t e r a s i n g l e n e o n a t a l i n j e c t i o n of 100 jag TP (mean LQ = 20, Edwards & B u r g e , 1971). T h i s s u g g e s t s t h a t t h e g e r b i l may be more 143 s e n s i t i v e t o t h e d e f e m i n i z i n g a c t i o n of exogenous TP t h a n a r e t h e r a t and mouse. I t seems u n l i k e l y t h a t t h e f a i l u r e t o o b s e r v e s i g n i f i c a n t l e v e l s o f r e c e p t i v i t y i n T P - t r e a t e d f e m a l e s was due s o l e l y t o t h e dose of e s t r o g e n a d m i n i s t e r e d s i n c e even t h e a d m i n i s t r a t i o n o f P a f t e r p r o l o n g e d EB t r e a t m e n t d i d n o t g r e a t l y enhance s e x u a l r e s p o n d i n g i n t h e s e a n i m a l s . T h i s would s u g g e s t t h a t t h e a n i m a l s ' a b i l i t y t o r e s p o n d t o e s t r o g e n was r e d u c e d . T h u s , i t seems l i k e l y t h a t i n t h e g e r b i l , a s i n t h e r a t ( G r e e n e t a l . , 1969; Maurer & W o o l l e y , 1971; Tuohimaa & J o h n s o n , 1971), TP d e c r e a s e s e s t r o g e n b i n d i n g c a p a c i t y a n d / o r a l t e r s n e u r o n a l s t r u c t u r e s i n t h e b r a i n and t h i s r e s u l t s i n d e c r e a s e d l o r d o s i s r e s p o n d i n g . U n l i k e t h e r a t ( S o d e r s t e n , 1973), mouse (Edwards & B u r g e , 1971), and h a m s t e r ( J o h n s o n , 1975) w h i c h e x h i b i t s i g n i f i c a n t i n c r e a s e s i n m o u n t i n g b e h a v i o u r a f t e r a s i n g l e i n j e c t i o n o f TP w i t h i n 48 h r o f b i r t h , t h e f e m a l e g e r b i l f a i l e d t o e x h i b i t any m a j o r i n c r e a s e i n m o u n t i n g b e h a v i o u r , r e g a r d l e s s of t h e TP dose a d m i n i s t e r e d . However, b e c a u s e c o n t r o l m a l e s d i d n o t e x h i b i t h i g h l e v e l s o f male s e x u a l b e h a v i o u r , t h e s e r e s u l t s a r e d i f f i c u l t t o i n t e r p r e t . I t i s c o n c e i v a b l e t h a t n e o n a t a l TP t r e a t m e n t was p r o v i d e d o u t s i d e t h e s e n s i t i v e p e r i o d f o r b e h a v i o u r a l m a s c u l i n i z a t i o n . A n o t h e r p o s s i b i l i t y i s t h a t more p r o l o n g e d TP t r e a t m e n t i s n e c e s s a r y f o r t h e e l i c i t a t i o n o f male s e x u a l b e h a v i o u r i n T P - t r e a t e d g e r b i l s . E x p e r i m e n t 12 i n d i c a t e d t h a t p r e - p l u s p o s t n a t a l TP t r e a t m e n t a l s o f a i l e d t o e l i c i t male s e x u a l a c t i v i t y . The p o s s i b i l i t y t h a t t h e t r e a t m e n t d u r a t i o n i n E x p e r i m e n t 12 was a l s o t o o s h o r t o r t h a t t h e s e n s i t i v e p e r i o d was a g a i n m i s s e d can n o t be e l i m i n a t e d . However, a l l o t h e r 1 44 r o d e n t s examined t o d a t e e x h i b i t a t l e a s t an i n c r e a s e i n m o u n t i n g b e h v i o u r a f t e r s i m i l a r p e r i n a t a l TP t r e a t m e n t . T h i s p l u s t h e low l e v e l s of male s e x u a l b e h a v i o u r e x h i b i t e d by a l l a n i m a l s , i n c l u d i n g i n t a c t m a l e s , d u r i n g most t e s t s o f male s e x u a l b e h a v i o u r s u g g e s t e d t h a t some o t h e r f a c t o r ( e . g . , t h e n e o n a t a l i n j e c t i o n p r o c e d u r e o r t h e c o n s e q u e n c e s of i n j e c t i o n s t r e s s i n p r e g n a n t a n i m a l s ) m i g h t have been i n f l u e n c i n g b e h a i v o u r . In an a t t e m p t t o d e t e r m i n e i f i n j e c t i o n s p e r se were r e s p o n s i b l e f o r t h e a b s e n c e of male s e x u a l b e h a v i o u r , a d d i t i o n a l c o n t r o l g r o u p s were t e s t e d . T h e s e r e s u l t s i n d i c a t e d t h a t i n j e c t i o n s p e r se d i d n o t d e c r e a s e male s e x u a l b e h a v i o u r i n a d u l t h o o d . F u r t h e r m o r e , even n o n - i n j e c t e d m ales e x h i b i t e d f a i r l y low l e v e l s o f s e x u a l a c t i v i t y , s u g g e s t i n g t h a t some o t h e r f a c t o r m i ght be r e s p o n s i b l e . One f a c t o r w h i c h has not r e c e i v e d a g r e a t d e a l of a t t e n t i o n f r o m i n v e s t i g a t o r s c o n c e r n s t h e e f f e c t s of h o u s i n g d i f f e r e n t s p e c i e s w i t h i n one c o l o n y room. I t has been f o u n d t h a t t h e r e p r o d u c t i v e c y c l e of t h e r a t i s a l t e r e d by t h e p r e s e n c e o f h a m s t e r s i n t h e same c o l o n y (Weizenbaum, M c C l i n t o c k , & A d l e r , 1977). To t h e b e s t o f my knowledge, t h e r e i s no p u b l i s h e d s t u d y r e l a t e d t o t h e e f f e c t s o f mixed h o u s i n g on g e r b i l r e p r o d u c t i o n . However, i t i s p o s s i b l e t h a t t h e p r e s e n c e of r a t s i n t h e same c o l o n y room i s s t r e s s f u l t o t h e g e r b i l . In t h e p r e s e n t e x p e r i m e n t s , t h e p r e s e n c e o f r a t odour c o u l d have t h e o r e t i c a l l y e x e r t e d an e f f e c t p r e n a t a l l y , p r e p u b e r t a l l y , o r b o t h . However, i t i s u n l i k e l y t h a t e f f e c t s a r e e x e r t e d p o s t p u b e r t a l l y b e c a u s e n o r m a l c o p u l a t o r y b e h a v i o u r i s o b s e r v e d i n g e r b i l s b r o u g h t i n t o t h e p r e s e n t c o l o n y a f t e r m a t u r i t y . P r e n a t a l a n d / o r p r e p u b e r t a l 145 e f f e c t s m i g h t o c c u r i f r a t o d o u r s were s t r e s s f u l t o t h e g e r b i l . L o n g - t e r m s t r e s s i n c r e a s e s a d r e n a l s e c r e t i o n s ( H a t c h e t a l . , 1963), some of w h i c h c o u l d a c t upon t h e d e v e l o p i n g f e t u s ( v i a m a t e r n a l c i r c u l a t i o n ) o r on t h e p r e p u b e r t a l a n i m a l . A l t h o u g h t h e e x a c t mechanism o f a c t i o n and t h e a c c o m p a n y i n g p h y s i o l o g i c a l a n d / o r n e u r o l o g i c a l a l t e r a t i o n s r e m a i n t o be d e t e r m i n e d , t h e f i n d i n g t h a t o n l y male s e x u a l b e h a v i o u r a p p e a r s t o be a f f e c t e d s u g g e s t s a t l e a s t two p o s s i b i l i t i e s . F i r s t , f e m a l e s e x u a l b e h a v i o u r i s more r e f l e x i v e t h a n male s e x u a l b e h a v i o u r . F o r example, d e c o r t i c a t i o n d e c r e a s e s male r a t s e x u a l r e s p o n s e s but has no e f f e c t on f e m a l e r a t s e x u a l r e s p o n s e s ( G o r z a l k a & Mogenson, 1977, pp. 179). I t i s p o s s i b l e t h a t , b e c a u s e f e m a l e s e x u a l b e h a v i o u r i s more r e f l e x i v e t h a t male s e x u a l b e h a v i o u r , i t i s l e s s l i k e l y t o be i n f l u e n c e d by v a r i o u s f a c t o r s . Thus, i n t h e p r e s e n t e x p e r i m e n t s , t h e d e c r e a s e i n male s e x u a l a c t i v i t y w i t h o u t a d e c r e a s e i n f e m a l e s e x u a l a c t i v i t y may r e f l e c t a g r e a t e r s u s c e p t i b i l i t y o f t h e mechanisms r e g u l a t i n g male s e x u a l b e h a v i o u r t o e x t r a n e o u s i n f l u e n c e s r a t h e r t h a n any change i n t h e hormones r e g u l a t i n g t h e b e h a v i o u r . S econd, t h e b e h a v i o u r a l c h a n g e s may be r e l a t e d t o a l t e r a t i o n s i n a n d r o g e n l e v e l s a n d / o r t h e a b i l i t y t o r e s p o n d t o a n d r o g e n s . M i l d l y s u p p o r t i v e of t h i s i s t h e f i n d i n g t h a t a g r e a t e r number of v e h i c l e c o n t r o l m a l e s i n E x p e r i m e n t 11 and v e h i c l e m a l e s t r e a t e d p r e - and p o s t n a t a l l y i n E x p e r i m e n t 12 e x h i b i t e d some component of male s e x u a l b e h a v i o u r d u r i n g TP a d m i n i s t r a t i o n t h a n when t e s t e d w h i l e i n t a c t . However, i t i s a l s o p o s s i b l e t h a t t h e i n c r e a s e was a f u n c t i o n of r e p e a t e d t e s t i n g . A t p r e s e n t , t h e r e i s no way t o d i f f e r e n t i a t e between t h e s e p o s s i b i l i t i e s . 1 46 The a b s e n c e o f m o u n t i n g b e h a v i o u r , f o r w h a t e v e r r e a s o n , i n t h e p r e s e n c e o f p a r t i a l and f u l l p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n T P - t r e a t e d f e m a l e s i s i n t r i g u i n g . As f a r as I have been a b l e t o d e t e r m i n e , p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n o t h e r r o d e n t s has a l w a y s been a c c o m p a n i e d by a t l e a s t an i n c r e a s e i n m o u n t i n g b e h a v i o u r . The o p p o s i t e e f f e c t , b e h a v i o u r a l m a s c u l i n i z a t i o n i n t h e a b s e n c e o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n , has been o b s e r v e d i n T P - t r e a t e d f e m a l e r a t s (Ward, 1969). The r e s u l t s o f Ward (1969) and o t h e r s ( e . g . , A l l e v a e t a l . , 1969; C o n i g l i o & C lemens, 1970) s u g g e s t t h a t , i n t h e r a t and h a m s t e r , t h e p e r i o d o f p h y s i o l o g i c a l m a s c u l i n i z a t i o n i s c o n t a i n e d w i t h i n or o v e r l a p s w i t h t h e s e n s i t i v e p e r i o d f o r b e h a v i o u r a l m a s c u l i n i z a t i o n . The r e s u l t s o f t h e p r e s e n t e x p e r i m e n t s s u g g e s t t h a t t h e g e r b i l may d i f f e r f r o m o t h e r r o d e n t s i n t h a t t h e s e n s i t i v e p e r i o d s f o r b e h a v i o u r a l and f o r p h y s i o l o g i c a l m a s c u l i n i z a t i o n m ight be non-o v e r l a p p i n g . However, u n t i l t h e p e r i o d f o r b e h a v i o u r a l m a s c u l i n i z a t i o n i n t h e g e r b i l i s c l e a r l y d e t e r m i n e d , t h i s r e m a i n s s p e c u l a t i o n . The p r e s e n c e o f p a r t i a l and f u l l p h y s i o l o g i c a l m a s c u l i n i z a t i o n i n t h e a b s e n c e o f male s e x u a l b e h a v i o u r s u g g e s t s t h a t , i f some e x t r a n e o u s f a c t o r i s r e s p o n s i b l e f o r t h e low l e v e l s o f male s e x u a l b e h a v i o u r o b s e r v e d , i t does not a p p e a r t o be a f f e c t i n g t h e a b i l i t y o f p e r i p h e r a l t i s s u e s t o r e s p o n d t o TP p r e - or p o s t p u b e r t a l l y . E x p e r i m e n t s 11 and 12 i n d i c a t e d t h a t s c e n t g l a n d s i z e and a n o g e n i t a l d i s t a n c e were a f f e c t e d by TP d o s e and t h e t i m e of TP a d m i n i s t r a t i o n . Thus, p r e p u b e r t a l TP was c a p a b l e o f e x e r t i n g e f f e c t s on p e r i p h e r a l t i s s u e s . F u r t h e r m o r e , t h e a b i l i t y of p e r i p h e r a l t i s s u e s t o r e s p o n d t o 1 47 a n d r o g e n s i n a d u l t h o o d i s a p p a r e n t l y n ot a l t e r e d i n t h e s e a n i m a l s . S c e n t g l a n d s i z e i n a d u l t h o o d i s d e t e r m i n e d t o a v e r y l a r g e e x t e n t by c i r c u l a t i n g g o n a d a l s t e r o i d s . C a s t r a t i o n l e a d s t o e v e n t u a l d i s s a p p e a r a n c e o f t h e s c e n t g l a n d and TP t r e a t m e n t r e v e r s e s t h i s e f f e c t (Blum & T h i e s s e n , 1971; Owen & T h i e s s e n , 1973; Y a h r , 1981; Y a h r , Newman & S t e p h e n s , 1979; Yahr & T h i e s s e n , 1972). A l l a n i m a l s i n E x p e r i m e n t s 11 and 12 e x h i b i t e d s c e n t g l a n d s t h a t were n o r m a l i n a p p e a r a n c e and a c t i v e l y s e c r e t i n g sebum a t t h e end o f TP a d m i n i s t r a t i o n , i n d i c a t i n g t h a t e xogenous TP was c a p a b l e o f e x e r t i n g e f f e c t s on p e r i p h e r a l t i s s u e s i n a d u l t h o o d . T h e r e f o r e , i f t h e d e c r e a s e i n male s e x u a l b e h a v i o u r was due t o d e c r e a s e d r e s p o n s i v e n e s s t o a n d r o g e n s , t h e d e c r e a s e d r e s p o n s i v e n e s s i s p r o b a b l y l i m i t e d t o t h e CNS. T h i s does n o t , however, p r e c l u d e t h e p o s s i b i l i t y t h a t t h e p r o d u c t i o n o f t e s t i c u l a r a n d r o g e n s was a l s o r e d u c e d s i n c e t h e amount of TP r e q u i r e d t o r e s t o r e s c e n t g l a n d a p p e a r a n c e i s l e s s t h a n t h a t r e q u i r e d f o r t h e r e s t o r a t i o n of male s e x u a l a c t i v i t y ( Y a h r , 1981). T h u s , i f some e x t r a n e o u s f a c t o r was r e s p o n s i b l e f o r t h e low l e v e l of male s e x u a l b e h a v i o u r o b s e r v e d i n t h e p r e s e n t e x p e r i m e n t s , i t may e x e r t i t s a c t i o n by d e c r e a s i n g t e s t i c u l a r a n d r o g e n l e v e l s as w e l l a s by a l t e r i n g t h e c a p a c i t y o f t h e CNS t o r e s p o n d t o a n d r o g e n s . The e f f e c t s o f o v a r i a n s t e r o i d s on f o o d i n t a k e and body w e i g h t i n t h e male g e r b i l were d i f f i c u l t t o a s s e s s b e c a u s e c a s t r a t i o n may have been e x e r t i n g d e l a y e d e f f e c t s . However, t h e f i n d i n g t h a t a n d r o g e n s (Maass & Wade, 1977) a r e no more e f f e c t i v e t h a n o v a r i a n s t e r o i d s i n a l t e r i n g f o o d i n t a k e and body w e i g h t i n t h e male g e r b i l w h i l e o v a r i a n s t e r o i d s c l e a r l y a l t e r 1 48 f o o d i n t a k e and body w e i g h t i n t h e f e m a l e g e r b i l s u g g e s t s t h a t o v a r i a n s t e r o i d s may be t h e p r i m a r y h o r m o n a l r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t i n t h i s s p e c i e s . I t was h y p o t h e s i z e d t h a t , i n s p e c i e s where o v a r i a n s t e r o i d s a r e t h e p r i m a r y r e g u l a t o r s of f o o d i n t a k e and body w e i g h t , t h e p r e s e n c e of a n d r o g e n s d u r i n g t h e p e r i o d o f s e x u a l d i f f e r e n t i a t i o n would have a d e f e m i n i z i n g e f f e c t . The p r e s e n t e x p e r i m e n t s i n d i c a t e t h a t o v a r i a n s t e r o i d s a r e p r o b a b l y t h e p r i m a r y h o r m o n a l r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t i n t h e g e r b i l . F u r t h e r m o r e , b o t h male and f e m a l e g e r b i l s a r e c l e a r l y d e f e m i n i z e d by t h e p r e s e n c e of a n d r o g e n s d u r i n g t h e p e r i o d o f s e x u a l d i f f e r e n t i a t i o n . T h e s e r e s u l t s s u p p o r t t h e h y p o t h e s i s t h a t t h e e x t e n t o f p e r i n a t a l a n d r o g e n - i n d u c e d d e f e m i n i z a t i o n can be u s e d t o p r e d i c t w h i c h sex s t e r o i d w i l l e x e r t t h e m a j o r i n f l u e n c e on a d u l t f o o d i n t a k e and body w e i g h t (and v i c e v e r s a ) . A l t h o u g h t h e e v i d e n c e i n s u p p o r t of a c o n n e c t i o n between s p e c i e s d i f f e r e n c e s i n t h e e x t e n t o f a n d r o g e n - i n d u c e d d e f e m i n i z a t i o n and i n w h i c h g o n a d a l s t e r o i d i s t h e p r i m a r y h o r m o n a l r e g u l a t o r o f i n t a k e and w e i g h t i n a d u l t h o o d i s i n d i r e c t , t h e r e i s a t l e a s t one p l a u s i b l e e x p l a n a t i o n f o r a c o n n e c t i o n . T h e r e i s now s u f f i c i e n t e v i d e n c e t o c o n c l u d e t h a t t h e p r e s e n c e o f a n d r o g e n s d u r i n g d i f f e r e n t i a t i o n p r o d u c e s d e f i n i t e a l t e r a t i o n s i n n e u r o n a l s t r u c t u r e and s t e r o i d b i n d i n g c a p a c i t y o f t h e b r a i n ( d e B o l d , 1978; D o r n e r & S t a u d t , 1968, 1969; F i e l d & Raisman, 1971; G o r s k i e t a l . , 1978; G r e e n e t a l , 1969; G r e e n o u g h e t a l . , 1977; M aurer & W o o l l e y , 1971; N i s h i z u k a & A r a i , 1981; Tuohimaa & J o h a n s s o n , 1971). I t i s p o s s i b l e t h a t 1 49 s p e c i e s d i f f e r e n c e s i n t h e d e f e m i n i z i n g a c t i o n of p e r i n a t a l a n d r o g e n s r e f l e c t more g e n e r a l i n t e r s p e c i f i c d i f f e r e n c e s i n t h e o v e r a l l o r g a n i z a t i o n a l e f f e c t s of p e r i n a t a l a n d r o g e n s . F o r example, p e r i n a t a l a n d r o g e n s may e x e r t somewhat d i f f e r e n t e f f e c t s on s t e r o i d b i n d i n g c a p a c i t y o r s t e r o i d s e n s i t i v i t y i n d i f f e r e n t s p e c i e s . The m a j o r i t y o f a n d r o g e n r e l a t e d n e u r o n a l c h a n g e s r e p o r t e d so f a r o c c u r i n an a r e a i m p l i c a t e d i n t h e h o r m o n a l r e g u l a t i o n of f o o d i n t a k e , s e x u a l b e h a v i o u r , and o t h e r m o t i v a t e d b e h a v i o u r s , t h e h y p o t h a l a m i c a r e a . T h e r e f o r e , i f t h e more g e n e r a l o r g a n i z a t i o n a l e f f e c t s o f p e r i n a t a l a n d r o g e n s do d i f f e r between s p e c i e s , t h i s may w e l l be r e f l e c t e d by between s p e c i e s d i f f e r e n c e s i n b e h a v i o u r s m e d i a t e d by t h e h y p o t h a l a m u s . Thus, t h e r e i s a t l e a s t some i n d i r e c t s u p p o r t f o r t h e s p e c u l a t i o n t h a t t h e d i f f e r e n c e between t h e ha m s t e r and o t h e r r o d e n t s i n t h e ho r m o n a l r e g u l a t i o n of f o o d i n t a k e and body w e i g h t i s r e l a t e d t o s p e c i e s d i f f e r e n c e s i n t h e more g e n e r a l o r g a n i z i n g a c t i o n s o f p e r i n a t a l a n d r o g e n s . U n f o r t u n a t e l y , d a t a w h i c h c o u l d r e v e a l t h e p r e s e n c e or a b s e n c e o f s p e c i e s d i f e r e n c e s i n t h e s e a r e a s a r e r e l a t i v e l y s p a r s e . I t does a p p e a r t h a t t h e sex d i f f e r e n c e s i n t h e d e n d r i t i c b r a n c h i n g of t h e p r e o p t i c a r e a o b s e r v e d by Greenough e t a l . , (1977) i n t h e ha m s t e r a r e s i m i l a r t o t h o s e o b s e r v e d by Raisman & F i e l d (1972) i n t h e r a t . However, i t i s not c l e a r t h a t t h e e x t e n t o f t h e sex d i f f e r e n c e o b s e r v e d i s t h e same between t h e s e two s p e c i e s . F e d e r e t a l . (1974) have o b s e r v e d d i f f e r e n t i a l r a t e s o f e s t r a d i o l u p t a k e i n r a t s , h a m s t e r s , and g u i n e a p i g s . T h i s d i f f e r e n c e a p p e a r s r e l a t e d t o t h e s e n s i t i v i t y of e a c h s p e c i e s t o e s t r a d i o l i n t h e i n d u c t i o n of r e c e p t i v i t y , w i t h t h e more 1 50 s e n s i t i v e r o d e n t s ( r a t s and g u i n e a p i g s ) e x h i b i t i n g t h e g r e a t e s t u p t a k e ( F e d e r e t a l . , 1974). I t i s p o s s i b l e t h a t t h i s d i f f e r e n c e between t h e h a m s t e r , r a t and g u i n e a p i g r e f l e c t s d i f f e r e n t i a l e f f e c t s o f p e r i n a t a l a n d r o g e n s on e s t r a d i o l b i n d i n g c a p a c i t y . However, i t i s c l e a r t h a t a g r e a t d e a l of f u r t h e r r e s e a r c h i s r e q u i r e d b e f o r e i n t e r s p e c i f i c d i f f e r e n c e s i n t h e o r g a n i z a t i o n a l e f f e c t s o f a n d r o g e n s c a n be c l e a r l y d e t e r m i n e d . 1.51 SECTION I I I Summary and. C o n c l u s i o n s E x p e r i m e n t s 1-4 i n d i c a t e d t h a t t h e f e m a l e g e r b i l i s s i m i l a r t o o t h e r f e m a l e r o d e n t s s t u d i e d t o d a t e i n t h a t e s t r o g e n and p r o g e s t e r o n e a r e t h e p r i m a r y r e g u l a t o r s of s e x u a l r e c e p t i v i t y . However, t h e g e r b i l does a p p e a r t o be more d e p e n d e n t t h a n t h e r a t , g u i n e a p i g , and some mouse s t r a i n s ( s e e Uphouse, W i l s o n , & S c h l e s i n g e r , 1970) on t h e s y n e r g i s t i c a c t i o n o f p r o g e s t e r o n e w i t h e s t r o g e n f o r t h e i n d u c t i o n o f h i g h l e v e l s o f r e c e p t i v i t y . In t h i s r e s p e c t , t h e g e r b i l i s s i m i l a r t o t h e h a m s t e r , w h i c h i s a l s o f a i r l y d e p e n d e n t on t h e a c t i o n of P f o r i n d u c t i o n o f maximal r e c e p t i v i t y d u r i n g a c u t e e s t r o g e n a d m i n i s t r a t i o n . F e d e r e t a l . (1974) f o u n d t h a t t h e r a t e o f e s t r o g e n u p t a k e was s l o w e r i n t h e h a m s t e r t h a n i n t h e r a t and g u i n e a p i g and s u g g e s t e d t h a t t h i s was r e f l e c t e d i n t h e l o w e r s e n s i t i v i t y o f t h e ham s t e r t o e s t r o g e n - i n d u c e d r e c e p t i v i t y . I t i s p l a u s i b l e t h a t t h e g e r b i l , l i k e t h e h a m s t e r , may a l s o have a s l o w e r r a t e o f e s t r o g e n u p t a k e t h a n do t h e r a t and g u i n e a p i g and t h a t t h i s i s r e s p o n s i b l e f o r t h e g e r b i l ' s g r e a t e r p r o g e s t e r o n e - d e p e n d e n c e o r l o w e r s e n s i t i v i t y t o e s t r o g e n . H a m s t e r s e x h i b i t g r e a t e r p l a s m a e s t r a d i o l l e v e l s d u r i n g t h e e s t r o u s c y c l e t h a n do r a t s ( B a r a n c z u k & G r e e n w a l d , 1973) and, a p p a r e n t l y , g u i n e a p i g s ( F e d e r e t a l . , 1974). T h i s l e d F e d e r e t a l . (1974) t o c o n c l u d e " i t a p p e a r s t h a t t h e h i g h e r t h e endogenous l e v e l o f a s t e r o i d , t h e l e s s a v i d i s t h e u p t a k e of t h a t s t e r o i d ( r e l a t i v e t o pla s m a ) and t h e l e s s s e n s i t i v e i s t h e a n i m a l t o t h a t s t e r o i d . " . To t h e b e s t o f my knowledge, t h e g e r b i l i s t h e o n l y o t h e r r o d e n t 1 52 examined so f a r w h i c h i s s i m i l a r t o t h e h a m s t e r i n t h e r e q u i r e m e n t o f c o m p a r a t i v e l y h i g h a c u t e e s t r o g e n d o s e s f o r t h e e l i c i t a t i o n of maximal r e c e p t i v i t y . F u r t h e r m o r e , t h e dose o f c h r o n i c e s t r o g e n r e q u i r e d t o e l i c i t h i g h l e v e l s of r e c e p t i v i t y i n t h e g e r b i l i s g r e a t e r t h a n t h a t r e q u i r e d by o t h e r r o d e n t s i n c l u d i n g t h e h a m s t e r ( C a r t e r , M i c h a e l , & M o r r i s , 1973). Thus, i n v e s t i g a t i o n i n t o t h e l e v e l s of e s t r o g e n s e c r e t e d by t h e g e r b i l d u r i n g t h e e s t r o u s c y c l e as w e l l a s e x a m i n a t i o n of t h e r a t e o f e s t r o g e n u p t a k e would p r o v i d e f u r t h e r e v i d e n c e f o r t h e v a l i d i t y o f t h e s p e c u l a t i o n t h a t , a s endogenous s t e r o i d l e v e l s i n c r e a s e , s e n s i t i v i t y a n d / o r u p t a k e d e c r e a s e . F u r t h e r i n f o r m a t i o n on t h i s c o u l d p r o v e v a l u a b l e s i n c e i t i s p o s s i b l e t h a t t h e s l o w e r u p t a k e o f e s t r o g e n o b s e r v e d i n t h e hamster i s r e l a t e d t o t h e o r g a n i z i n g a c t i o n of p e r i n a t a l a n d r o g e n s . I f t h i s i s t h e c a s e , one would e x p e c t t o f i n d t h a t t h e g e r b i l w ould have an u p t a k e p a t t e r n s i m i l a r t o t h e r a t and g u i n e a p i g s i n c e a l l t h r e e s p e c i e s a r e d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s ( w h i c h a l t e r s t e r o i d u p t a k e ) . However, i f t h e d e c r e a s e d r a t e o f u p t a k e i n t h e h a m s t e r r e f l e c t s an a d a p t i v e r e s p o n s e t o r e l a t i v e l y h i g h e s t r o g e n t i t e r s , t h e n one m ight e x p e c t t h e g e r b i l t o be s i m i l a r i n t h a t r e s p e c t t o t h e h a m s t e r s i n c e b o t h s p e c i e s e x h i b i t l o w e r e s t r o g e n s e n s i t i v i t y r e l a t i v e t o r a t s and g u i n e a p i g s . F u r t h e r e x a m i n a t i o n o f t h e s e d i f f e r e n c e s would a i d i n d e t e r m i n i n g t h e r e l a t i v e c o n t r i b u t i o n s o f p e r i n a t a l a n d r o g e n s v e r s u s g e n e t i c f a c t o r s on s t e r o i d s e n s i t i v i t y . E x p e r i m e n t s 5 and 6 i n d i c a t e d t h a t h o u s i n g c o n d i t i o n s d i d n o t a l t e r r e c e p t i v i t y i n t h e f e m a l e g e r b i l . T h i s c o n t r a s t s w i t h r e s u l t s o b t a i n e d i n t h e r a t , where i s o l a t i o n i n c r e a s e s s e x u a l 1 53 r e s p o n d i n g , p r e s u m a b l y v i a a d r e n a l s t e r o i d s . I t was s u g g e s t e d t h a t t h e a b s e n c e of a d i f f e r e n t i a l h o u s i n g e f f e c t i n t h e g e r b i l may r e f l e c t e i t h e r s p e c i e s d i f f e r e n c e s i n a d r e n a l s t e r o i d s or d i f f e r e n c e s i n b r a i n s e n s i t i v i t y t o p a r t i c u l a r s t e r o i d s . Thus, even i f d i f f e r e n t i a l h o u s i n g d i d a l t e r a d r e n a l s t e r o i d s e c r e t i o n , t h e s e c h a n g e s need n o t be r e f l e c t e d i n s e x u a l r e s p o n d i n g . E x p e r i m e n t s 5-8 i n d i c a t e d t h a t a d r e n a l e c t o m y s i g n i f i c a n t l y d e c r e a s e d r e c e p t i v i t y i n t h e g e r b i l . T h i s e f f e c t i s not o b s e r v e d i n t h e r a t , where a d r e n a l e c t o m y f a c i l i t a t e s r a t h e r t h a n i n h i b i t s r e c e p t i v i t y ( G r a y & G o r z a l k a , 1980; G o r z a l k a & R a i b l e , 1981). I t was a l s o f o u n d t h a t p a r t i c u l a r c o m b i n a t i o n s o f a d r e n a l s t e r o i d s e l i m i n a t e d any d i f f e r e n c e i n r e c e p t i v i t y due t o a d r e n a l e c t o m y i n t e s t s where a n i m a l s r e c e i v e d EB a l o n e but n o t i n t e s t s where a n i m a l s r e c e i v e d P i n c o n j u n c t i o n w i t h EB. T h i s s u g g e s t s t h a t some a s p e c t o f a d r e n a l e c t o m y o t h e r t h a n l o s s of a d r e n a l s t e r o i d s may be, i n p a r t , r e s p o n s i b l e f o r a r e d u c e d s e n s i t i v i t y t o t h e s y n e r g i s t i c a c t i o n o f P w i t h EB. F u r t h e r m o r e , i t would a p p e a r t h a t t h e g e r b i l , u n l i k e o t h e r f e m a l e r o d e n t s s t u d i e d t o d a t e , r e q u i r e s a d r e n a l s t e r o i d s i n a d d i t i o n t o EB and P f o r t h e e l i c i t a t i o n of maximal r e c e p t i v i t y . A g r e a t d e a l of f u r t h e r i n v e s t i g a t i o n w i l l be r e q u i r e d b e f o r e t h e p r e c i s e n a t u r e o f t h i s r e l a t i o n s h i p i s d e t e r m i n e d . The r e s u l t s o f E x p e r i m e n t s 5-8 add t o t h e g r o w i n g amount of e v i d e n c e t h a t a d r e n a l s t e r o i d s c a n a l t e r s e x u a l r e c e p t i v i t y i n t h e f e m a l e r o d e n t . F u r t h e r m o r e , a t l e a s t i n t h e r a t , t h e r e a r e i n d i c a t i o n s t h a t s t r e s s a l t e r s c i r c u l a t i n g l e v e l s o f a d r e n a l s t e r o i d s i n an amount s u f f i c i e n t t o a l t e r s e x u a l r e s p o n d i n g . I t 1 54 i s t h u s somewhat s u r p r i s i n g t h a t t h e p o s s i b l e e f f e c t s o f s t r e s s on e x p e r i m e n t a l r e s u l t s a r e o f t e n o v e r l o o k e d . F o r example, a q u i c k g l a n c e t h r o u g h t h e l i t e r a t u r e i n d i c a t e s t h a t t h e m a j o r i t y of r e s e a r c h e r s do not r e p o r t h o u s i n g c o n d i t i o n s . A l t h o u g h t h i s would not seem t o c r e a t e p r o b l e m s a s l o n g as t h e h o u s i n g c o n d i t i o n s were t h e same f o r a l l g r o u p s , i t c o u l d c r e a t e p r o b l e m s f o r t h o s e t r y i n g t o r e p l i c a t e e x p e r i m e n t a l f i n d i n g s . I t i s o f t e n p o s s i b l e t h a t many o f t h e a p p a r e n t c o n t r a d i c t i o n s i n t h e l i t e r a t u r e on f e m a l e r e c e p t i v i t y a c t u a l l y r e f l e c t p r o c e d u r a l d i f f e r e n c e s . F o r example, p r o c e d u r a l d i f f e r e n c e s between e x p e r i m e n t s c o u l d p r o d u c e d i f f e r e n t e f f e c t s on a d r e n a l s t e r o i d s e c r e t i o n . T h i s , i n t u r n , c o u l d r e s u l t i n d i f f e r e n t l e v e l s of r e c e p t i v i t y between e x p e r i m e n t s . The r e s u l t s of E x p e r i m e n t 9 i n d i c a t e d t h a t o v a r i e c t o m y d e c r e a s e d f o o d i n t a k e and body w e i g h t i n t h e f e m a l e g e r b i l , an e f f e c t n o t f o u n d i n t h e r a t , mouse, g u i n e a p i g and h a m s t e r . T r e a t m e n t w i t h e s t r o g e n r e s t o r e d f o o d i n t a k e and body w e i g h t l e v e l s t o t h o s e e x h i b i t e d by c o n t r o l a n i m a l s . I t was s u g g e s t e d t h a t n o r e p i n e p h r i n e may be a l t e r e d by e s t r o g e n , a s i s t h e c a s e f o r t h e r a t . However, i f e s t r o g e n does i n f l u e n c e NE l e v e l s , e i t h e r t h e e f f e c t s of e s t r o g e n on NE o r t h e e f f e c t s o f NE on f o o d i n t a k e d i f f e r from t h e e f f e c t s o b s e r v e d i n t h e r a t . One c o u l d d i f f e r e n t i a t e between t h e s e p o s s i b i l i t i e s by e x a m i n i n g t h e e f f e c t of NE on f o o d i n t a k e and t h e n d e t e r m i n i n g t h e e f f e c t of EB on NE l e v e l s . The h o r m o n a l r e g u l a t i o n o f f o o d i n t a k e and body w e i g h t i n t h e g e r b i l d i f f e r s from o t h e r r o d e n t s e xamined t o d a t e i n a n o t h e r i m p o r t a n t r e s p e c t . In a l l o t h e r r o d e n t s examined so 1 55 f a r , i t a p p e a r s t h a t t h e p r i m a r y g o n a d a l hormone t h a t r e g u l a t e s f o o d i n t a k e and body w e i g h t f o r t h a t s p e c i e s i s , t o a g r e a t e x t e n t , r e s p o n s i b l e f o r t h e sex d i f f e r e n c e i n f o o d i n t a k e and body w e i g h t . F o r example, i n t h e r a t , where f e m a l e s a r e l i g h t e r t h a n males and o v a r i a n s t e r o i d s a r e t h e p r i m a r y r e g u l a t o r s of f o o d i n t a k e and body w e i g h t , o v a r i e c t o m y l e a d s t o i n c r e a s e s i n f o o d i n t a k e and body w e i g h t w h i c h s u b s t a n t i a l l y r e d u c e t h e sex d i f f e r e n c e s . In t h e h a m s t e r , t h e male i s l i g h t e r t h a n t h e f e m a l e , a n d r o g e n s a r e t h e p r i m a r y h o r m o n a l r e g u l a t o r s of f o o d i n t a k e and body w e i g h t and c a s t r a t i o n i n c r e a s e s f o o d i n t a k e and body w e i g h t l e v e l s i n t h e male t o t h o s e o b s e r v e d i n t h e f e m a l e . In t h e g e r b i l , as i n t h e f e m a l e r a t , t h e f e m a l e w e i ghs l e s s t h a n t h e male and o v a r i a n hormones a p p e a r t o be t h e p r i m a r y r e g u l a t o r s of f o o d i n t a k e and body w e i g h t . However, i n t h e f e m a l e g e r b i l , u n l i k e t h e f e m a l e r a t , o v a r i e c t o m y l e a d s t o d e c r e a s e s i n f o o d i n t a k e and body w e i g h t , f u r t h e r i n c r e a s i n g t h e sex d i f f e r e n c e s . To t h e b e s t o f my knowledge, t h i s i s t h e f i r s t known r o d e n t i n w h i c h f a c t o r s o t h e r t h a n c i r c u l a t i n g hormone l e v e l s c l e a r l y c o n t r i b u t e t o t h e s e x u a l d i m o r p h i s m o b s e r v e d i n f o o d i n t a k e and body w e i g h t r e g u l a t i o n . P e r i n a t a l a n d r o g e n s may c o n t r i b u t e t o t h i s s e x u a l d i m o r p h i s m . Body w e i g h t d a t a c o l l e c t e d f r o m E x p e r i m e n t s 11 and 12 i n d i c a t e t h a t n e o n a t a l a n d r o g e n i z a t i o n i n c r e a s e d f e m a l e body w e i g h t t o t h a t o b s e r v e d i n c o n t r o l m a l e s . T h i s s u g g e s t s t h a t p a r t o f t h e d i m o r p h i s m o b s e r v e d i n a d u l t h o o d i s due t o an o r g a n i z a t i o n a l e f f e c t o f p e r i n a t a l a n d r o g e n t h a t i s i n d e p e n d e n t o f any a c t i v a t i o n a l e f f e c t s of sex s t e r o i d s l a t e r i n l i f e . I f t h i s i s t h e c a s e , n e o n a t a l c a s t r a t i o n s h o u l d r e s u l t i n a permanent r e d u c t i o n i n 156 a d u l t body w e i g h t w h i c h would n o t be i n f l u e n c e d by c i r c u l a t i n g hormones i n a d u l t h o o d . P r e v i o u s r e s e a r c h has i n d i c a t e d t h a t t h e o r g a n i z a t i o n a l a c t i o n o f p e r i n a t a l a n d r o g e n s i n f l u e n c e t h e a c t i v a t i o n a l e f f e c t s o f hormones on f o o d i n t a k e and body w e i g h t i n a d u l t h o o d . U n t i l now, t h e r e has been l i t t l e e v i d e n c e t h a t sex s t e r o i d s e x e r t o r g a n i z a t i o n a l e f f e c t s on f o o d i n t a k e and body w e i g h t t h a t a r e i n d e p e n d e n t o f t h e l a t e r a c t i v a t i o n a l e f f e c t s o f sex s t e r o i d s . The f e m a l e g e r b i l c o u l d t h u s p r o v i d e a u s e f u l t o o l f o r t h e e x a m i n i a t i o n o f t h e s e e f f e c t s . The e f f e c t s o f o v a r i a n s t e r o i d s on f o o d i n t a k e and body w e i g h t i n t h e male g e r b i l ( E x p e r i m e n t 10) were l e s s c l e a r t h a n t h o s e o b t a i n e d f o r t h e f e m a l e . C a s t r a t i o n a p p e a r e d t o e x e r t d e l a y e d e f f e c t s on f o o d i n t a k e and, p e r h a p s , body w e i g h t , w h i c h may have masked any e f f e c t s o f o v a r i a n s t e r o i d t r e a t m e n t . A l t h o u g h i t i s p o s s i b l e t h a t n e i t h e r o v a r i a n s t e r o i d s nor a n d r o g e n s i n f l u e n c e f o o d i n t a k e and body w e i g h t i n t h e male g e r b i l , i t seems more l i k e l y t h a t , a s i n t h e f e m a l e h a m s t e r ( M o r i n & Flemming, 1978), t h e e f f e c t s a r e s i m p l y n o t r o b u s t . E x p e r i m e n t s 9 and 10 a l s o i n d i c a t e d t h a t , i n t h e g e r b i l , t h e s y s t e m r e g u l a t i n g f o o d i n t a k e and body w e i g h t was more s e n s i t i v e t o EB t h a n t h e s y s t e m r e g u l a t i n g s e x u a l b e a h v i o u r . T h i s d o e s not a p p e a r t o be t h e c a s e i n t h e r a t . One c o u l d h y p o t h e s i z e t h a t t h e d i f f e r e n t i a l s e n s i t i v i t y t o EB o b s e r v e d i n t h e f o o d i n t a k e and s e x u a l b e h a v i o u r s y s t e m s o f t h e g e r b i l r e f l e c t s a d i f f e r e n c e i n e s t r a d i o l b i n d i n g c a p a c i t y o f t h e two s y s t e m s . I n v e s t i g a t i o n o f t h e d i s t r i b u t i o n o f r a d i o l a b l e d e s t r a d i o l i n s p e c i f i c h y p o t h a l a m i c a r e a s c o u l d p r o v i d e some i n t e r e s t i n g i n f o r m a t i o n . F o r example, t h e l a t e r a l h y p o t h a l a m u s 157 (LH) and v e n t r o m e d i a l h y p o t h a l a m i c n u c l e i (VMH) a r e c o n s i d e r e d q u i t e i m p o r t a n t i n t h e r e g u l a t i o n o f f o o d i n t a k e and body w e i g h t (Wade, 1976). L e s i o n s of t h e VMH l e a d t o h y p e r p h a g i a w h i l e l e s i o n s o f t h e LH p r o d u c e a p h a g i a ( C a r l s o n , 1977,pp. 356; E l l i s o n , S o r e n s o n , & J a c o b s , 1970). E v i d e n c e f r o m l e s i o n and s t i m u l a t i o n s t u d i e s i n d i c a t e s t h a t t h e p r e o p t i c a r e a of t h e h y p o t h a l a m u s (POA), t h e VMH, and t h e a n t e r i o r h y p o t h a l a m u s a r e i m p o r t a n t i n t h e r e g u l a t i o n o f s e x u a l b e h a v i o u r ( G o r s k i , 1976; K e l l y & P f a f f , 1978; P f a f f , 1980). I f , as may be t h e c a s e i n t h e g e r b i l , t h e s y s t e m r e g u l a t i n g f o o d i n t a k e has a g r e a t e r e s t r a d i o l b i n d i n g c a p a c i t y t h a n t h a t r e g u l a t i n g s e x u a l r e c e p t i v i t y , a g r e a t e r c o n c e n t r a t i o n o f e s t r a d i o l s h o u l d o c c u r i n t h e a r e a s m e d i a t i n g t h a t b e h a v i o u r . T h i s t y p e o f i n f o r m a t i o n c o u l d be compared between r o d e n t s i n w h i c h t h e s e n s i t i v i t y „ o f t h e f o o d i n t a k e and t h e s e x u a l b e h a v i o u r s y s t e m s t o EB a r e known. I n f o r m a t i o n on t h e b r a i n p a t t e r n s o f e s t r o g e n u p t a k e d o e s n o t e x i s t f o r t h e g e r b i l a l t h o u g h i t d o e s e x i s t f o r t h e r a t . A u t o r a d i o g r a p h i c s t u d i e s of e s t r a d i o l - c o n c e n t r a t i n g c e l l s i n t h e r a t b r a i n s u g g e s t t h a t t h e POA and a n t e r i o r h y p o t h a l a m u s ( s e x u a l b e h a v i o u r ) may c o n t a i n more e s t r o g e n - c o n c e n t r a t i n g c e l l s t h a n t h e VMH and LH ( f e e d i n g b e h a v i o u r and s e x u a l b e h a v i o u r ) but t h e s e d i f f e r e n c e s a r e v e r y s l i g h t ( P f a f f , 1980). T h e s e f i n d i n g s a r e c o n s i s t e n t w i t h t h e h y p o t h e s i s . However, no c o n c l u s i o n s c a n be drawn u n t i l o t h e r s p e c i e s have been examined and t h e d a t a compared. E x p e r i m e n t s 11 and 12 i n d i c a t e d t h a t n e o n a t a l and p r e - p l u s n e o n a t a l TP t r e a t m e n t d e f e m i n i z e d t h e f e m a l e g e r b i l and p r o d u c e d p a r t i a l t o f u l l p h y s i o l o g i c a l m a s c u l i n i z a t i o n but i t c o u l d n o t 158 be d e t e r m i n e d u n e q u i v o c a l l y whether b e h a v i o u r a l m a s c u l i n i z a t i o n o c c u r r e d . T h e s e r e s u l t s , i n c o n j u n c t i o n w i t h t h o s e f o u n d f o r o t h e r r o d e n t s may shed some l i g h t on a p r e s e n t c o n t r o v e r s y c o n c e r n i n g t h e d i f f e r e n t i a t i o n of s e x u a l b e h a v i o u r . T h r e e m o d els o f t h e d i f f e r e n t i a t i o n of s e x u a l b e h a v i o u r have been p r o p o s e d w i t h i n t h e l a s t two d e c a d e s , t h e l i n e a r o r u n i d i m e n s i o n a l model ( H a r r i s , 1964), t h e o r t h o g o n a l model (Whalen, 1974), and t h e o b l i q u e model ( R e i n i s c h , 1976). The u n i d i m e n s i o n a l model a r g u e s t h a t male and f e m a l e s e x u a l b e h a v i o u r a r e s e p a r a t e ends of a s i n g l e c o n t i n u u m ( F i g u r e 15a). T h u s , t h e d e g r e e o f m a s c u l i n i z a t i o n would be n e g a t i v e l y c o r r e l a t e d w i t h t h e d e g r e e of f e m i n i z a t i o n . However, as p r e v i o u s l y d i s c u s s e d , i t i s p o s s i b l e t o a c h i e v e f u l l b e h a v i o u r a l d e f e m i n i z a t i o n w i t h o u t f u l l b e h a v i o u r a l m a s c u l i n i z a t i o n . In f a c t , a s i n g l e i n j e c t i o n of TP a r o u n d t h e t i m e of b i r t h i s s u f f i c i e n t t o d e f e m i n i z e , but n o t f u l l y m a s c u l i n i z e , t h e f e m a l e r a t , mouse, and g e r b i l . F u r t h e r m o r e , a d u l t male and a n d r o g e n i z e d f e m a l e h a m s t e r s c a n e x h i b i t b o t h male and f e m a l e s e x u a l b e h a v i o u r . Thus, t h e u n i d i m e n s i o n a l model does n o t seem t o a c c o u n t f o r some of t h e b e h a v i o u r a l d a t a now a v a i l a b l e . I t d o e s , however, d e s c r i b e t h e d i f f e r e n t i a t i o n p r o c e s s f o r some of t h e p h y s i o l o g i c a l d a t a . F o r example, a n o g e n i t a l d i s t a n c e i s a u n i d i m e n s i o n a l phenomenon. Female r o d e n t s have t h e s h o r t e s t a n o g e n i t a l d i s t a n c e p o s s i b l e w h i l e males have t h e l o n g e s t , i n t e r m e d i a t e d i s t a n c e s r e p r e s e n t a movement t o w a r d s one end o f t h e c o n t i n u u m and away from t h e o t h e r . The o r t h o g o n a l model v i e w s m a s c u l i n i z a t i o n and f e m i n i z a t i o n as s e p a r a t e c o n t i n u a ( F i g u r e 15b). In t h i s model, 159 F i g u r e 15. M o d e l s of s e x u a l d i f f e r e n t i a t i o n . In t h e l i n e a r o r u n i d i m e n s i o n a l model ( a ) , m a s c u l i n i z a t i o n and f e m i n i z a t i o n a r e v i e w e d a s s e p a r a t e ends o f a s i n g l e c o n t i n u u m . In t h e o r t h o g o n a l model ( b ) , m a s c u l i n i z a t i o n and f e m i n i z a t i o n a r e v i e w e d as s e p a r a t e , o r t h o g o n a l c o n t i n u a t h a t a r e not n e c e s s a r i l y c o r r e l a t e d . In t h e o b l i q u e model ( c ) , m a s c u l i n i z a t i o n and f e m i n i z a t i o n a r e v i e w e d as s e p a r a t e c o n t i n u a b ut t h e a s s u m p t i o n i s made t h a t , i n t h e n a t u r a l c o u r s e o f d e v e l o p m e n t , t h e two a r e , t o some d e g r e e , c o r r e l a t e d . 160 MASCULINIZED FEMINIZED FEMINIZED MASCULINIZED DEMASCULINIZED DEFEMINIZED MASCULINIZED FEMINIZED DEFEMINIZED DEMASCULINIZED 161 m a s c u l i n i z a t i o n - d e m a s c u l i n i z a t i o n c o m p r i s e one c o n t i n u u m t h a t i s o r t h o g o n a l t o a f e m i n i z a t i o n - d e f e m i n i z a t i o n c o n t i n u u m . M a s c u l i n i z a t i o n and f e m i n i z a t i o n a r e n o t n e c e s s a r i l y c o r r e l a t e d . T h i s model c r e a t e s a t o t a l o f f o u r q u a d r a n t s w i t h i n w h i c h s e x u a l l y d i m o r p h i c b e h a v i o u r s may f a l l , m a s c u l i n i z a t i o n -d e f e m i n i z a t i o n , m a s c u l i n i z a t i o n - f e m i n i z a t i o n , d e m a s c u l i n i z a t i o n -d e f e m i n i z a t i o n , and d e m a s c u l i n i z a t i o n - f e m i n i z a t i o n . When s p e a k i n g s t r i c t l y o f s e x u a l b e h a v i o u r , we f i n d e x a m ples o f e a c h o f t h e f o u r c a t e g o r i e s i n t h e a n i m a l d a t a . The male r a t , g e r b i l , and a n d r o g e n i z e d f e m a l e r a t f a l l i n t o t h e m a s c u l i n i z a t i o n - d e f e m i n i z a t i o n q u a d r a n t . The f e m a l e r a t and g e r b i l and t h e n e o n a t a l l y c a s t r a t e d male r a t f a l l i n t o t h e f e m i n i z a t i o n - d e m a s c u l i n i z a t i o n q u a d r a n t . The male and a n d r o g e n i z e d f e m a l e h a m s t e r f a l l i n t o t h e m a s c u l i n i z a t i o n -f e m i n i z a t i o n q u a d r a n t . F i n a l l y , i f one c o n s i d e r s t h a t p e r i n a t a l a n d r o g e n s d i d not f u l l y m a s c u l i n i z e t h e f e m a l e g e r b i l i n E x p e r i m e n t s 11 and 12, one would c o n c l u d e t h a t t h e a n d r o g e n i z e d f e m a l e g e r b i l f a l l s i n t o t h e d e f e m i n i z a t i o n - d e m a s c u l i n i z a t i o n q u a d r a n t . T h u s , t h i s model c o v e r s a l l p o s s i b i l i t i e s s u g g e s t e d by t h e a v a i l a b l e b e h a v i o u r a l d a t a on s e x u a l b e h a v i o u r i n r o d e n t s . The a p p l i c a t i o n o f t h i s model t o some o f t h e b e h a v i o u r a l d a t a and much of t h e p h y s i o l o g i c a l d a t a does n o t , however, seem a p p r o p r i a t e . In f a c t , t h e o r t h o g o n a l model i s c l e a r l y u n n e c e s s a r y i f one i s d i s c u s s i n g q u a n t i t a t i v e d i f f e r e n c e s o f a s i n g l e f a c t o r w h i c h i s q u a l i t a t i v e l y s i m i l a r i n b o t h s e x e s . F o r example, s c e n t m a r k i n g b e h a v i o u r i n male and f e m a l e g e r b i l s i s s i m i l a r i n q u a l i t y between t h e s e x e s a l t h o u g h t h e q u a n t i t y o f s c e n t m a r k i n g b e h a v i o u r d i s p l a y e d d i f f e r s 1 62 between m a l e s and f e m a l e s . B e c a u s e q u a n t i t y i s t h e o n l y d i m e n s i o n i n w h i c h t h e s e x e s c a n d i f f e r , t h e b e h a v i o u r i s n e c e s s a r i l y u n i d i m e n s i o n a l . A g e r b i l can n o t e x h i b i t more t h a n one p a t t e r n o f s c e n t m a r k i n g . T h u s , t h e l e v e l of m a r k i n g b e h a v i o u r e x h i b i t e d by e a c h o f t h e s e x e s r e p r e s e n t o p p o s i t e ends of a s i n g l e c o n t i n u u m . S i m i l a r l y , a n o g e n i t a l d i s t a n c e s c a n n o t be b o t h m a s c u l i n i z e d and f e m i n i z e d or d e f e m i n i z e d and d e m a s c u l i n i z e d . Thus, t h e o r t h o g o n a l model i s u s e f u l i n t h e d e s c r i p t i o n of s e x u a l b e h a v i o u r but s h o u l d n o t be r e a d i l y a p p l i e d t o o t h e r s e x u a l l y d i m o r p h i c f a c t o r s u n l e s s i t i s c l e a r t h a t t h e r e a r e q u a l i t a t i v e sex d i f f e r e n c e s i n t h o s e f a c t o r s ( e . g . , u r i n a t i o n p o s t u r e i n d o g s ) . The o b l i q u e model ( F i g u r e 15c) was p r o p o s e d by R e i n i s c h as a m o d i f i c a t i o n o f t h e o r t h o g o n a l model and s t a t e s t h a t " m a s c u l i n i z a t i o n and d e f e m i n i z a t i o n , as w e l l as f e m i n i z a t i o n and d e m a s c u l i n i z a t i o n , a r e c o r r e l a t e d , but t h a t one i s n o t n e c e s s a r i l y d e t e r m i n e d , under a l l c i r c u m s t a n c e s , by t h e o t h e r . " ( R e i n i s c h , 1976). I t i s d i f f i c u l t t o see how t h i s model d i f f e r s i n any i m p o r t a n t r e s p e c t from t h e o r t h o g o n a l model p r o p o s e d by Whalen ( 1 9 7 4 ) . The r a t i o n a l e p r e s e n t e d by R e i n i s c h (1976) f o r t h e m o d i f i c a t i o n s of t h e o r t h o g o n a l model a p p e a r s t o be t h a t t h e o r t h o g o n a l model i s b a s e d on d a t a f r o m s h o r t - t e r m p e r i n a t a l TP a d m i n i s t r a t i o n s t u d i e s r a t h e r t h a n t h o s e w h i c h u s e d more p r o l o n g e d t r e a t m e n t . She seems t o s u g g e s t t h a t t h e f o r m e r do n o t r e f l e c t t h e n a t u r a l c o u r s e o f e v e n t s d u r i n g d i f f e r e n t i a t i o n . U n f o r t u n a t e l y , i t i s n o t c l e a r why R e i n i s c h f e e l s t h a t t h e o r t h o g o n a l model does n o t encompass b o t h t h e n a t u r a l c o u r s e of e v e n t s and t h e e x p e r i m e n t a l r e s u l t s o b t a i n e d i n t h i s a r e a o f 1 63 r e s e a r c h . F u r t h e r m o r e , i t i s not c l e a r t h a t t h e o b l i q u e model a d e q u a t e l y c o v e r s t h e e x p e r i m e n t a l d a t a . In f a c t , i t i s n o t c l e a r what, e x a c t l y , i s s t a t e d by t h e o b l i q u e m o d e l . F o r R e i n i s c h does n o t d i s c u s s t h e a p p l i c a b i l i t y o f h e r model t o t h e e x p e r i m e n t a l d a t a . In a d d i t i o n , t h e r e a p p e a r s t o be an e r r o r i n t h e g r a p h i c r e p r e s e n t a t i o n o f t h e m o d e l . Thus, we a r e p r e s e n t e d w i t h a model w h i c h u s e s m a s c u l i n i z a t i o n - f e m i n i z a t i o n a s one c o n t i n u u m and d e m a s c u l i n i z a t i o n - d e f e m i n i z a t i o n a s t h e o t h e r c o n t i u n u u m , r e s u l t i n g i n two q u a d r a n t s w h i c h a r e i m p o s s i b i l i t i e s ( m a s c u l i n i z a t i o n - d e m a s c u l i n i z a t i o n , f e m i n i z a t i o n -d e f e m i n i z a t i o n ) . However, i f one assumes t h a t t h i s i s a p r i n t i n g e r r o r and t h a t t h e c o n t i n u a a r e s i m i l a r t o t h o s e i n t h e o r t h o g o n a l model, i s i s s t i l l n o t c l e a r t h a t t h e o b l i q u e model p r o v i d e s t h e ' b e s t f i t ' f o r t h e d a t a . Thus, of t h e t h r e e models p r o p o s e d , t h e u n i d i m e n s i o n a l o r l i n e a r model seems b e s t f o r d e s c r i b i n g q u a n t i t a t i v e d i f f e r e n c e s i n q u a l i t a t i v e l y s i m i l a r s e x u a l l y d i m o r p h i c b e h a v i o u r s . The o r t h o g o n a l model, on t h e o t h e r hand, i s b e s t a p p l i e d t o q u a l i t a t i v e d i f f e r e n c e s i n s e x u a l l y d i m o r p h i c b e h a v i o u r s . W h i l e t h e models d i s c u s s e d above p r o v i d e a good d e s c r i p t i o n o f t h e r e s u l t s o b t a i n e d i n p e r i n a t a l TP s t u d i e s , t h e y do l i t t l e i n r e v e a l i n g why t h e s e t y p e s o f r e s u l t s a r e o b t a i n e d . W i t h t h e w e a l t h o f e v i d e n c e t h a t has a c c u m u l a t e d o v e r r e c e n t y e a r s , d e s c r i p t i v e models no l o n g e r seem s u f f i c i e n t t o d e a l w i t h t h e p r e s e n t knowledge. A l t h o u g h I know o f no model y e t g e n e r a t e d t h a t d e a l s w i t h t h e c o n c e p t o f s e n s i t i v e p e r i o d s , i t i s t h i s c o n c e p t t h a t most r e s e a r c h e r s now r e f e r t o when d i s c u s s i n g t h e i r d a t a . I t a p p e a r s from a v a r i e t y o f s t u d i e s ( e . g . , A l l e v a e t 1 64 a l . , 1969; C o n i g l i o & Clemens, 1970; Ward, 1969) t h a t t h e s e n s i t i v e p e r i o d f o r p h y s i o l o g i c a l m a s c u l i n i z a t i o n of e x t e r n a l g e n i t a l i a o c c u r s d u r i n g t h e e a r l y p o r t i o n o f t h e s e n s i t i v e p e r i o d f o r b e h a v i o u r a l m a s u c l i n i z a t i o n , a t l e a s t i n t h e r a t , h a m s t e r , and g u i n e a p i g . E a c h of t h e s e p e r i o d s a p p e a r s t o r e q u i r e a s p e c i f i c d u r a t i o n o f a n d r o g e n e x p o s u r e as w e l l . Thus, a l t h o u g h s e v e r a l d a y s o f p r e - p l u s n e o n a t a l TP t r e a t m e n t a r e r e q u i r e d t o e l i c i t f u l l b e h a v i o u r a l m a s c u l i n i z a t i o n i n t h e r a t , a s i n g l e e x p o s u r e t o a n d r o g e n s c a n d e f e m i n i z e t h e f e m a l e r a t . I f one now r e t u r n s t o t h e o r t h o g o n a l model, t h e c i r c u m s t a n c e s t h a t would r e s u l t i n e a c h of t h e f o u r q u a d r a n t s become c l e a r . I f an a n i m a l i s b e h a v i o u r a l l y m a s c u l i n i z e d and d e f e m i n i z e d , e i t h e r t h e s e n s i t i v e p e r i o d f o r d e f e m i n i z a t i o n must o c c u r w i t h i n t h e s e n s i t i v e p e r i o d f o r b e h a v i o u r a l m a s c u l i n i z a t i o n o r a n d r o g e n s must be p r e s e n t d u r i n g b o t h t h e s e n s i t i v e p e r i o d f o r f e m i n i z a t i o n and t h a t f o r m a s c u l i n i z a t i o n . In t h e male and a n d r o g e n i z e d f e m a l e r a t , d e f e m i n i z a t i o n can be b r o u g h t a b o u t by a s i n g l e i n j e c t i o n of a n d r o g e n s d u r i n g t h e s e n s i t i v e p e r i o d f o r m a s c u l i n i z a t i o n , s u g g e s t i n g t h a t t h e p e r i o d f o r f e m i n i z a t i o n i s c o n t a i n e d w i t h i n t h e p e r i o d f o r m a s c u l i n i z a t i o n . I f an a n i m a l i s b e h a v i o u r a l l y m a s c u l i n i z e d and f e m i n i z e d , e i t h e r t h e r e i s no s e n s i t i v e p e r i o d f o r d e f e m i n i z a t i o n , t h e s e n s i t i v e p e r i o d s f o r d e f e m i n i z a t i o n and m a s c u l i n i z a t i o n do n o t o v e r l a p s u f f i c i e n t l y f o r one t o g r e a t l y e f f e c t t h e o t h e r , o r a n d r o g e n l e v e l s d u r i n g d i f f e r e n t i a t i o n a r e s u f f i c i e n t t o m a s c u l i n i z e but n o t d e f e m i n i z e t h e a n i m a l . The l a t t e r w ould a p p e a r t o be t h e c a s e f o r t h e male h a m s t e r . F e m i n i z a t i o n i s t h e r e s u l t o f an a b s e n c e o f sex s t e r o i d s d u r i n g 165 t h e s e n s i t i v e p e r i o d f o r d e f e m i n i z a t i o n . S i m i l a r l y , d e m a s c u l i n i z a t i o n i s t h e r e s u l t o f an a b s e n c e o f a p p r o p r i a t e s t e r o i d s d u r i n g t h e s e n s i t i v e p e r i o d f o r m a s c u l i n i z a t i o n . F e m i n i z a t i o n and d e m a s c u l i n i z a t i o n would t h u s o c c u r when sex s t e r o i d s were a b s e n t d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n . Examples o f t h i s a r e t h e f e m a l e and f u n c t i o n a l l y c a s t r a t e d male r a t , mouse, h a m s t e r , and g u i n e a p i g , t h e f e m a l e g e r b i l , and, I s u s p e c t , t h e n e o n a t a l l y c a s t r a t e d male g e r b i l . F i n a l l y , d e m a s c u l i n i z a t i o n and d e f e m i n i z a t i o n c o u l d o c c u r i f (1) t h e s e n s i t i v e p e r i o d s f o r m a s c u l i n i z a t i o n and d e f e m i n i z a t i o n d i d n o t o v e r l a p and (2) t h e a p p r o p r i a t e s t e r o i d s were a b s e n t d u r i n g t h e p e r i o d f o r m a s c u l i n i z a t i o n and p r e s e n t f o r t h e p e r i o d o f f e m i n i z a t i o n . T h i s m i g h t be t h e c a s e f o r t h e a n d r o g e n t r e a t e d f e m a l e g e r b i l s i n E x p e r i m e n t s 11 and 12 a l t h o u g h f u r t h e r s t u d y i s n e c e s s a r y b e f o r e t h i s c a n be d e t e r m i n e d . F i n a l l y , i n e a c h of t h e s e s i t u a t i o n s , t h e p r e s e n c e o f a n d r o g e n s d u r i n g o n l y a p o r t i o n o f one o r more s e n s i t i v e p e r i o d s would r e s u l t i n d e g r e e s of m a s c u l i n i z a t i o n a n d / o r d e f e m i n i z a t i o n . Thus, a l t h o u g h t h e o r t h o g o n a l model p r o v i d e s a good d e s c r i p t i o n of e x p e r i m e n t a l r e s u l t s , t h e c o n c e p t of s e n s i t i v e p e r i o d s w h i c h may o v e r l a p p r o v i d e s an e x p l a n a t i o n o f why v a r y i n g d e g r e e s of s e x u a l b e h a v i o u r may be o b s e r v e d . I t was h y p o t h e s i z e d t h a t o v a r i a n s t e r o i d s would be t h e p r i m a r y r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t i n a n i m a l s w h i c h were d e f e m i n i z e d by t h e p r e s e n c e o f a n d r o g e n s d u r i n g s e x u a l d i f f e r e n t i a t i o n w h i l e a n d r o g e n s would be t h e p r i m a r y h o r m o n a l r e g u l a t o r s of f o o d i n t a k e and body w e i g h t i n a n i m a l s w h i c h were n o t d e f e m i n i z e d by t h e p r e s e n c e of a n d r o g e n s d u r i n g 166 s e x u a l d i f f e r e n t i a t i o n . On t h e b a s i s o f E x p e r i m e n t 9 and 10 p l u s t h e s t u d y by Maass & Wade (1977) w h i c h i n d i c a t e d t h a t o v a r i a n s t e r o i d s were p r o b a b l y t h e p r i m a r y h o r m o n a l r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t i n t h e g e r b i l , i t was p r e d i c t e d t h a t g e r b i l s would be d e f e m i n i z e d by t h e p r e s e n c e o f a n d r o g e n s d u r i n g t h e p e r i o d of s e x u a l d i f f e r e n t i a t i o n . E x p e r i m e n t s 11 and 12 i n d i c a t e d t h a t t h i s was i n d e e d t h e c a s e . Thus, t h e g e r b i l i s s i m i l a r t o t h e r a t , mouse, and g u i n e a p i g w h i c h a r e a l s o d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s and have o v a r i a n s t e r o i d s a s t h e p r i m a r y r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t . T h e s e r o d e n t s d i f f e r from t h e h a m s t e r w h i c h i s n o t d e f e m i n i z e d by p e r i n a t a l a n d r o g e n s and where a n d r o g e n s a r e t h e p r i m a r y r e g u l a t o r s o f f o o d i n t a k e and body w e i g h t . The c o n c e p t of o v e r l a p p i n g s e n s i t i v e p e r i o d s f o r t h e o r g a n i z a t i o n a l a c t i o n s o f p e r i n a t a l a n d r o g e n s on s e x u a l l y d i m o r p h i c b e h a v i o u r s c a n p r o v i d e a t l e a s t one e x p l a n a t i o n o f i n t e r s p e c i f i c d i f f e r e n c e s i n t h e h o r m o n a l r e g u l a t i o n of f o o d i n t a k e , body w e i g h t , and s e x u a l b e h a v i o u r . F o r example, i n t h e r a t , p e r i n a t a l a n d r o g e n s d e c r e a s e e s t r a d i o l - b i n d i n g c a p a c i t y w h i l e i n c r e a s i n g a n d r o g e n s e n s i t i v i t y . In male r a t s , g e r b i l s , g u i n e a p i g s , and m i c e , a n d r o g e n s may be p r e s e n t d u r i n g t h e e n t i r e s e n s i t i v e p e r i o d f o r d i f f e r e n t i a t i o n of s e x u a l b e h a v i o u r but o n l y a p o r t i o n of t h e s e n s i t i v e p e r i o d f o r d i f f e r e n t i a t i o n o f f o o d i n t a k e and body w e i g h t . T h i s would l e a d t o f u l l m a s c u l i n i z a t i o n o f s e x u a l b e h a v i o u r . However, t h e p r e s e n c e o f a n d r o g e n s d u r i n g o n l y a p o r t i o n o f t h e s e n s i t i v e p e r i o d f o r f o o d i n a k e and -body w e i g h t c o u l d d e c r e a s e s e n s i t i v i t y t o EB w i t h o u t s u b s t a n t i a l l y i n c r e a s i n g s e n s i t i v i t y t o a n d r o g e n . The f e m a l e 167 r a t , g e r b i l , mouse, and g u i n e a p i g , l a c k i n g p e r i n a t a l a n d r o g e n s , would be more s e n s i t i v e t h a n t h e male t o t h e e f f e c t s o f EB on f o o d i n t a k e , body w e i g h t , and s e x u a l b e h a v i o u r . The h a m s t e r , on t h e o t h e r hand, i s r e l a t i v e l y i n s e n s i t i v e t o e s t r o g e n , even i n t h e a b s e n c e o f p e r i n a t a l a n d r o g e n s , as i n d i c a t e d by t h e f i n d i n g t h a t u n t r e a t e d f e m a l e h a m s t e r s a r e l e s s s e n s i t i v e t h a n r a t s t o EB i n t h e i n d u c t i o n o f r e c e p t i v i t y . I t i s o f i n t e r e s t t o n o t e t h a t t h e f e m a l e g e r b i l , l i k e t h e f e m a l e h a m s t e r , i s r e l a t i v e l y i n s e n s i t i v e t o e s t r o g e n f o r t h e i n d u c t i o n o f s e x u a l r e c e p t i v i t y . However, t h e f e m a l e g e r b i l i s more s e n s i t i v e t h a n t h e h a m s t e r t o t h e e f f e c t s of e s t r o g e n on f o o d i n t a k e and body w e i g h t r e g u l a t i o n . T h i s , p l u s i n t e r s p e c i f i c d i f f e r e n c e s i n e s t r o g e n s e n s i t i v i t y ( e . g . , r a t v e r s u s h a m s t e r ) s u g g e s t t h a t g e n e t i c f a c t o r s , i n a d d i t i o n t o p e r i n a t a l a n d r o g e n s , p l a y a r o l e i n d e t e r m i n i n g i n t e r s p e c i e s d i f f e r e n c e s i n hormone s e n s i t i v i t i e s . I t i s c l e a r t h a t a g r e a t d e a l of f u r t h e r r e s e a r c h w i l l be r e q u i r e d b e f o r e an u n d e r s t a n d i n g o f t h e a c t i v a t i o n a l e f f e c t s of p e r i n a t a l a n d r o g e n s on n e u r a l mechanisms u n d e r l y i n g s e x u a l l y d i m o r p h i c b e h a v i o u r s w i t h i n a s p e c i e s , and d i f f e r e n c e s i n s e x u a l l y d i m o r p h i c b e h a v i o u r s between s p e c i e s i s r e a c h e d . However, t h e c o n c e p t o f s e n s i t i v e p e r i o d s i n c o n j u n c t i o n w i t h e v i d e n c e f o r a n d r o g e n - i n d u c e d n e u r o n a l a l t e r a t i o n s , p o i n t t o w a r d s a p r o m i s i n g a r e a o f r e s e a r c h . A l t h o u g h much d a t a needs t o be c o l l e c t e d on e x i s t i n g l a b o r a t o r y r o d e n t s , t h e need f o r new s p e c i e s o f r o d e n t s t o examine t h e g e n e r a l i t y o f s u p p o s e d mechanisms o f a c t i o n s h o u l d n o t be o v e r l o o k e d . The g e r b i l , d i f f e r i n g i n so many ways from o t h e r l a b o r a t o r y r o d e n t s , 168 p r o v i d e s one s o u r c e of c o m p a r a t i v e i n f o r m a t i o n and p r o m i s e s t o be an i n t e r e s t i n g new a d d i t i o n t o t h e p r e s e n t l i s t o f l a b o r a t o r y r o d e n t s . 169 REFERENCES Agren, G. S o c i a l and t e r r i t o r i a l b e h a v i o u r i n t h e M o n g o l i a n g e r b i l ( M e r i o n e s u n g u i c u l a t u s ) under s e m i n a t u r a l c o n d i t i o n s . B i o l o g y .and B e h a v i o u r . 1976, 267-285. A g r e n , G. P e r s i s t e n c e o f m a l e / f e m a l e s o c i a l r e l a t i o n s h i p s i n t h e M o n g o l i a n g e r b i l ( M e r i o n e s u n g u i c u l a t u s ) . B e h a v i o u r a l  P r o c e s s e s . 1980, 373-379. A g r e n , G. & M e y e r s o n , B . J . P r e f e r e n c e f o r p a i r - p a r t n e r i n t h e M o n g o l i a n g e r b i l . A c t a P h y s i o l o g i c a S c a n d i n a v i a ( s u p p l ) . 1973, 369, 82. A g r e n , G., & M e y e r s o n , B . J . S o c i o - s e x u a l b e h a v i o r i n t h e M o n g o l i a n g e r b i l . E x p e r i m e n t a l B r a i n R e s e a r c h ( s u p p l ) . 1975, 23, 5. A g r e n , G., & M e y e r s o n , B . J . I n f l u e n c e o f g o n a d a l hormones and s o c i a l h o u s i n g c o n d i t i o n s on a g o n i s t i c , c o p u l a t o r y , and r e l a t e d s o c i o - s e x u a l b e h a v i o u r i n t h e M o n g o l i a n g e r b i l ( M e r i o n e s u n g u i c u l a t u s ) . 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E f f e c t o f a s i n g l e p r e p u b e r t a l i n j e c t i o n of t e s t o s t e r o n e p r o p i o n a t e on l a t e r r e p r o d u c t i v e f u n c t i o n s o f t h e f e m a l e g o l d e n h a m s t e r . E n d o c r i n o l o g y . 1969, 85, 312-318. A n i s k o , J . J . C h r i s t e n s o n , T., & B u e h l e r , M.G. E f f e c t s of a n d r o g e n s on f i g h t i n g b e h a v i o r i n male and f e m a l e M o n g o l i a n g e r b i l s ( M e r i o n e s u n g u i c u l a t u s ) . Hormones and B e h a v i o r . 1973, 4, 199-208. 1 70 A n t o n - T a y , F. & Wurtman, R . J . N o r e p i n e p h r i n e : T u r n o v e r i n r a t b r a i n s a f t e r gonadectomy. S c i e n c e . 1 9 6 8 , 1 5 9 , 1 2 4 5 . Bapna, J . , N e f f , N.H., & C o s t a , E. A method f o r s t u d y i n g n o r e p i n e p h r i n e and s e r o t o n i n m e t a b o l i s m i n a n t e r i o r and p o s t e r i o r h y p o t h a l a m u s . 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