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The effect of oral arginine hydrochloride on growth hormone levels, body composition, performance… Macintyre, James Gillis 1986

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THE EFFECT OF ORAL ARGININE HYDROCHLORIDE ON GROWTH HORMONE L E V E L S , BODY COMPOSITION, PERFORMANCE AND BIOCHEMICAL PARAMETERS I N MALE RECREATIONAL RUNNERS By JAMES G I L L I S MACINTYRE B.Sc. U n i v e r s i t y o f T o r o n t o , 1974 M.D. The U n i v e r s i t y o f W e s t e r n O n t a r i o , 1978 A THESIS SUBMITTED I N PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTERS OF PHYSICAL EDUCATION in THE FACULTY OF GRADUATE STUDIES (PHYSICAL EDUCATION)  We a c c e p t t h i s  t h e s i s as conforming  to t h e r e q u i r e d  standard  THE UNIVERSITY OF B R I T I S H COLUMBIA A p r i l , 1986 ©James G i l l i s  M a c i n t y r e , 1986  ? 8  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 o f 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  it  and study.  f r e e l y a v a i l a b l e f o r reference  I further  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 o r by h i s o r her r e p r e s e n t a t i v e s .  Iti s  understood t h a t c o p y i n g o r 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 gain  s h a l l n o t be allowed without my  permission.  Department o f The U n i v e r s i t y o f B r i t i s h 2075 Wesbrook P l a c e Vancouver, Canada V6T 1W5 Date  1Q\  1/l(Lr  3o ,  Columbia  fife  written  ABSTRACT  Many  athletes  supplements levels,  w i l l  with  athletic  runners  an  f i t  daily  over  repeated  age  two  7  ANOVAs  were  increased  greater  than  that  related  to  maximal  oxygen  not  the  (p=0.13).  The  uptake  oxygen  in  or  subjects  reported the  AA.  with  significant  a  the  drugs.  biochemical GH  increases  did  not  response  significant  change  endurance,  i i  on  cross  GH  data.  and  to  AA  GH was  s t a t i s t i c a l  was  negatively related  to  administration  body  composition,  anaerobic  ingestion  response,  Although  reach  in  over,  MANOVA,  parameters.  improvements  plasma  the  AA  placebo cross-over  positively  in  training  physiological  by  AA  Oral  changes  hydrochloride in  of  response  to  and  hematological  subjective  Arginine  Data  the  aerobic  recreational  blind  at  in  twelve  lactose  analyzed  p<0.05).  or  or  and  GH  male  state  (AA)  (GH)  hypotheses  before,  was  AA,  hormone  anthropometric,  (r=0.69,  any  these  these  improvements  double  p<0.05)  biochemical  taking  in  the  and  steady  (r=-0.60,  uptake,  strength,  no  for  the  fat  a  that  growth  ml/kg/min)  in  composition  P,  result  maximal  to  % body  test  performed of  belief  serum  effect  51.2  periods  were  by  the  hydrochloride  used  were  significance  to  years)  administration  levels  did  anabolic  Comprehensive  body  in  increased  V02max  week  tests  and  acids  order  30.3  design.  the  performance  In  gm a r g i n i n e  biochemical after  in  attendant  (average  6.0  experimental  and  result  (average  ingested  and  amino  performance.  moderately  (P)  ingest  capacity, Five  training was  immunoreactive  or  of  the while  associated bioactive  growth  hormone  tested.  No  levels  significant  hematological, were  i n t h e 12 negative  male or  s t r e n g t h , body c o m p o s i t i o n  recreational positive  athletes  biochemical,  or performance  documented.  KEY WORDS: ARGININE, GROWTH HORMONE, ATHLETIC BODY COMPOSITION, OXYGEN UPTAKE  iii  PERFORMANCE,  changes  TABLE OF CONTENTS  ABSTRACT  i  L I S T OF TABLES  i  vi  L I S T OF FIGURES  v i i  ACKNOWLEDGEMENT  viii  INTRODUCTION  1  METHODS  3  Subjects  3  Study Design  3  Testing  4  Protocol  Statistical  Analysis  8  RESULTS  10  Subjects  10  Hormonal Response  10  Body  11  Composition  Aerobic  and A n a e r o b i c  Fitness  11  Strength Biochemical  12 and H e m a t o l o g i c a l  S u b j e c t i v e Changes  Parameters  12 12  DISCUSSION  18  CONCLUSIONS  24  REFERENCES  26  i v  APPENDIX: REVIEW OF LITERATURE  29  1- GROWTH HORMONE  30  1-1 STRUCTURE AND PRODUCTION  30  1-2 CONTROL OF SECRETION  30  1- 3 GH RELEASE  31  2- EFFECTS  37  2- 1 FUNCTION  37  2-2 METABOLIC  37  2-3 GROWTH  39  2-4 MUSCLE  40  2- 5 DISORDERS  46  3- GH AND ATHLETES  47  3- 1 INTRODUCTION  47  3-2 ADMINISTRATION  48  3-3 POTENTIAL USES  49  3-4 POTENTIAL PROBLEMS  51  v  L I S T OF TABLES  TABLE 1: HORMONAL RESPONSES  13  TABLE 2: ANTHROPOMETRIC DATA  14  TABLE 3: PERFORMANCE DATA  15  TABLE 4:  16.  STRENGTH  TABLE 5: HEMATOLOGY / BIOCHEMICAL  vi  17  LIST  FIGURE  1:  EXPERIMENTAL  FIGURE  2:  DATA  DESIGN  OF  /  FIGURES  TESTING  ANALYSIS..  PROTOCOL..  4 9  vii  ACKNOWLEDGEMENT  The  a u t h o r would  like  of Canada f o r f u n d i n g co-operation efforts Dr.  t o thank t h e S p o r t s this  Council  s t u d y . The p a r t i c i p a t i o n  of the subjects  are grat.efully  Medicine  was e s s e n t i a l ,  and  and t h e i r  t i m e and  a c k n o w l e d g e d . T h a n k s a r e a l s o due t o  D.B. C l e m e n t , t h e t h e s i s c o m m i t t e e c h a i r m a n , as w e l l as  c o m m i t t e e members D r . J . E . T a u n t o n and D r . D.C. M c K e n z i e f o r providing Drs.  invaluable assistance.  Prior,  assistance.  A d d i t i o n a l t h a n k s a r e due t o  G o r d o n , L i , and S c h u t z f o r t h e i r  e x p e r t i s e and  A s t u d y o f t h i s m a g n i t u d e w o u l d be i m p o s s i b l e t o  perform without considerable  hands on h e l p ,  and e t e r n a l  i s due t o D r . W. P a r k h o u s e , D r . G. M a t h e s o n , Ms. L y n d a Ms.  L y n n e Sawchuk, Ms. Y v e t t e  staff  of the l a b o r a t o r y ,  the  U.B.C. H e a l t h  due  t o my w i f e  V i g n a , Mr. B i l l  departments of  Sciences Centre H o s p i t a l . F i n a l l y ,  viii  Filsinger,  H e a r s t and t h e  pharmacy and r a d i o l o g y  Ginny, f o r her t o l e r a n c e ,  gratitude  patience  thanks i s  and a s s i s t a n c e .  INTRODUCTION The has  desire  led  aids  to  in  in  is  is  mass There  pure  GH,  cause  a  in  are  two  the  GH  is  a v a i l a b i l i t y . and  are  thus  It  has  acids no  w i l l  the  control  with  anabolic  of  various  been  endogenous  by  reported  that  documentation,  however,  performance.  In  in  GH  w i l l  result  not  to  increased  induced  muscle  atrophy  in  rats  no  prolonged appear  in  was  in  the  improvements  in  performance  with  periods  of  hypertrophied  acromegaly time but  and  develop are  in  -1-  a  fact  (GH), Growth  increase  in  lean  injection acids  p i t u i t a r y . i t s  cost  The  and  which use  and  easily  of  of  limited  accessible,  e l i t e  athletes.  administration  of  levels  There  is  have  an  (2,3).  increases no  w i l l  evidence  amino  that  improvements  in  GH  increases  has  reversed  same  has  administration  amino  led  performance  muscles  Patients  and  and  is  rats  but  and  an  to  GH  there  mass,  size  due  these  muscle  control  and  the  oral  that  hypophysectomized  however,  i t s  recreational  Furthermore, of  hormone  technology.  and  drugs  serum  use  (1).  from  the  ergogenic  steroid  growth  inexpensive  both  increases  effects  GH  performance  other  supplementation:  uncommom  to  anabolic  balance  ingestion  used  and  hormone,  animals  are  drugs  laboratory  nitrogen  acids  physical  endogenous  GH  of  their  anabolic  of  widely  effect.  of  current  r e l a t i v e l y  anabolic  of  methods  Amino  lead  use  elevate  positive  release  purified  improve  hypophysectomized  or  the  in  to  powerful  to  to  S t r i c t e r  attempts  a  lead  body  increase  undetectable  hormone w i l l  an  athletes  sport.  resulted which  of  animals  by  to  (4). GH  had  the  athletic in  Surgically-  administration, less  increase  in  (5).  excessive myopathy  in  GH which  functionally  levels the  weaker  over muscles  (6,7,8).  It  is  difficult  effects  of  amino a c i d i n g e s t i o n on h e a l t h y  studies  of  untrained,  acromegalic answer acids levels  three  affect  hypopituitary  This  questions.  cause s i g n i f i c a n t  detrimental amino  humans.  t o make a s s u m p t i o n s  s t u d y was  the  athletes  r a t s or performed  GH  release?  changes  acids?  -2-  performance? with  based  of  on ill,  i n an a t t e m p t  Does a m o d e r a t e  associated  possible  chronically  Does t h e o r a l a d m i n i s t r a t i o n  body c o m p o s i t i o n and  biochemical  about  to  amino  c h a n g e i n GH  Are t h e r e  the i n g e s t i o n  any of  METHODS Subjects Twelve personal  men  contacts  explanation runners  volunteered  in  of a  and the  steady  problems  and  athletic  a c t i v i t i e s  at  a  low  level.  a c t i v i t y keep  a  Study  record  study blind  (AA)  subjects They  medications.  allowed  were  A l l  if  it  instructed the  posted  consent  training.  any  was  their  was  had to  period  after  a  were  were  and  detailed  recreational  free  of  medical  Participation  in  been  and  was  diet  and  on-going  maintain of  notices  the  their  study  and  other  asked  to  a c t i v i t i e s .  (6.0  of  compounds  dispensed c l i n i c a l the  lactose)  pharmacist until  Testing  of  experiment,  conclusion conducted  oi at  the the  University  of  place  two  over  a l l  during  on  at  the  B r i t i s h  an  subjects  subjects  J.M.  the  7  Buchanan Columbia,  period Fitness  The  and  The  capsules the  over  drugs  by  the  1).  and  beginning and  A l l  at  Centre  each  testing  session morning,  of the  testing  Research  f i r s t  a  study.  and  the  were  medications  point,  (Figure  ingested  prepared  the  at  placebo  subjects  stomach.  On  amino  (P)  completed  cross  given  a  period,  conducted  with  were  using  BDH  assigned  mornings.  -3-  one  periods  monohydrochloride,  other.  had  week  subjects  gelatin  was  week  study  consecutive  seven  empty  randomly  the  second  The  appearing  who  two  L-Arginine  during  morning  identical  code  of  England)  every  in  over  design.  grams  (6.0  grams  conducted  cross-over  Poole,  the  of  throughout  Chemicals,  kept  informed  to  Design  double  the  state  They  of  gave  response  experiment.  taking  patterns  The  acid  not  a l l  in  at  was the  taking tests  of  body  composition,  performed. test,  On  a  assess  the  second  computerized body  samples  described  metabolic  responses  FIGURE  EXPERIMENTAL  TIME  0  GROUP  1  GROUP  2  the  were  taken  oxygen  uptake  were speed  had  an  anaerobic  scan  of  their  an  endurance  to  assess  thigh  run.  to Blood  hormonal  and  exercise.  DESIGN  /  TESTING  7  PROTICOL  WEEKS  14  <  PLACEBO  WEEKS  PLACEBO  >  >  AA  Protocol  Response  Blood  samples  biochemical including  and  GH,  second  was  was  intermittant  possible  GH GH  intravenous  taken  hematological  teflon  which  i n i t i a l  were  drawn  testing  indwelling  by  below  (C.T.)  performed  WEEKS  <  Hormonal  vein,  tomographic and  maximal  subjects  AA  Testing  the  to  and  morning,  composition,  as  1:  strength  day.  a  venous  The  maintained  was  catheter  of  with  surge  associated  with  line.  Immediately  Fasting  for  a  subsequent  stress  the  line  gauge  cephalic  blood  sampling  puncture  was  20  of  the  normal  of  morning a  in  levels, bloodwork,  the  had  placed  separate the  on  then  heparinized  after  -4-  hormonal  puncture  subjects  patent  infusions drawn  monitor  parameters.  intravenous  small  sample  via  to  saline. to  avoid  establishing established,  The the the the  test  drug  response order  (AA was  to kept  they  engaged  assessed  in  for  was  measured  the  30  the  fasting,  inactive  the  blood  hospital  same the  3  post  GH  to  avoid  samples  the  analyzed assay  P  (RIA)  samples  were  samples,  GH  samples testing  the  walk  to  to  day  GH  minutes.  In  the  subjects  only  a c t i v i t y  the  the  have  of  i t  the  radiology  response  with  the  to  exercise  conclusion  of  information  on  time,  was  a  120  minute  second  testing  collected  (9).  A  lactogen  a c t i v i t y  labelled,  session  were  Samples  were  saved  from  any  periods.  one  minutes  to  The  make  in  the  Ltd,  on  ice.  bioassay  was  performed  basis GH  -5-  of was  GH  and  pooled  stimulation calculated  two  at  the  both  The  (PRL)  assessed  by  of  minutes  samples  Minn.).  of  each  the were  radio-immuno  Prolactin  which  in  10  for  standard  and  the  done from  samples  Minneapolis, both  Active  being  to  and  analyzed  drug,  and  a  for  (10).  and  pooled  analyzed  the  centrifuged,  post  using  kept  transported  Aliquots  individual  duplicate,  and  were  subject  variation.  120  combined  on  they  they  inter-assay  in  was  where  (Kallestad  also  line  C.  were  technique  lymphocyte  drug  other  (baseline,  GH  kit  the  120  after  order  testing  samples  time  for  and  minutes  and  levels,  hormone  f i r s t  the  -70  a l l  exercise)  and  the of  with  time  to  at  GH  minute  In  mouth,  state.  for  at  10  run.  laboratory, o  frozen  batches  the the  conclusion  serum  AA  with  GH  response  on  As  the  Growth  sampling  on  interval,  scan.  GH  done  influences this  by  sample  five  in  period.  At  C.T.  another  slow  endurance  was  The  a  minute the  administered  with  during was  by  was  other  fasting  department  sample  P)  minimize  were  changes  or  cells  pooled by  RIA  the  total  of  Nb-2  subtracting  the  RIA  level  of  PRL  from  the  total  lactogen  a c t i v i t y  determined  by  bioassay .  Body  Composition Body  composition  skinfold  measurements  tomography proximal  was to  of  percentages  of  two  scans  measured  limb  width  femoral  fat  and  (11).  of  were  for  computations.  In  measures  fat  (12).  Aerobic  and  Anaerobic  Maximal  oxygen  the  2.66  continuously  Measurement  Cart  sites  3  event  of  analyzed areas  calculated  experienced  (thigh  and  (femoral  aberrant  the  area  and  averaged  anthropometrist  thigh  biceps,  and  c a l f ) ,  was  values  were  medial  and  and  average  wrist). used  the  measured then  the  was  measurements,  Density  using fat  and  condyles  and  cm  of  subscapular,  anterior  times,  these  uptake  rate -1  were  an  sites  the  15  two  using  converted  to  Fitness  i n i t i a l  every  2  and  After  m.sec  2  Computerized  cross-sectional then  through  thighs  were  separate  (triceps,  used.  protocol.  0.22  at  right  scans  abdominal,  repeated  treadmill  of  were  sites  at  were  percent  to  addition, 8  weighing,  The  and  weighing.  subjects'  total  muscle  landmarks  measurements  the  methods  circumference  bony  hydrostatic  on  supra-spinale,  A l l  closest  hydrostatic  The  In at  radiographically,  condyles.  muscle.  skinfolds  supra-iliac, c a l f ) ,  and  densiometric  those  over  assessed  performed  the  quantitative from  was  minute  was  determined  using  a  continuous  a  w a r m up p e r i o d t h e s u b j e c t s r a n a t -1 m.sec with the speed increased  u n t i l  sampled  and  interfaced  v o l i t i o n a l analyzed  into  -6-  a  fatigue.  by  Hewlett  a  Expired  Beckman Packard  an by  gases  Metabolic 3052A  Data  Acquisition every  System  fifteen  seconds.  as  the  The  ventilatory  the  average  curve  recording  of  Maximal  the  highest  threshold  of  respiratory  excess  was  CO  oxygen four  gas  exchange  consumption  consecutive  determined  by  elimination  was  15  determined  second  visual  (13).  variables  values.  inspection  Heart  of  rate  was  2 monitered Ky,  using  Oulu,  recalls  at  the  average  This  during  a  heart  30  Heart  Rate  calculates,  rate  for  accurate  Microcomputer stores  every  30  in  memory,  second  determination  of  (Escotek  period  the  and during  heart  rate  submaximal  heart  threshold.  endurance  response  Tester  which  allowed  ventilatory  Aerobic rate  Sport  Finland),  the  exercise.  a  and  was  blood  minute  run  evaluated lactate  at  a  through  levels  constant  at  the 10  minute  speed.  The  same  intervals speed  was  -1 used less  for  a l l  three  than  the  determined  on  measured  speed the  every  mobilization  runs,  10  and  Anaerobic  at  and the  f i r s t minutes  was  individually  ventilatory testing as  an  set  at  threshold  session.  indicator  0.44  that  Serum  of  m.sec  had  been  glucose  metabolic  was  substrate  u t i l i z a t i o n . capacity  was  determined  using  an  anaerobic  speed  o test.  The  speed  set  v o l i t i o n a l blood  treadmill  at  3.54  m.sec  ,and  fatigue  (14).  The  lactate  completion  was e l e v a t e d -1 the time  determination  of  the  Strength  of  to  a  slope  subjects to  was  ran  fatigue made  of  3  20  to  was  ,  the  with  point  recorded,  minutes  the  after  of  and  a  the  test.  Strength  muscles  were  the  measured  bicep,  tricep,  b i l a t e r a l l y  -7-  quadricep,  using  the  Cybex  and II  hamstring Isokinetic  Dynamometer. the  After  equipment, o -1 180  .sec  with  the  highest  .  and  Two  blood  each urea  phosphate, (LDH),  of  count  standard  Subject  and  hospital  the  questionnaire  A  were  monitored  Biochemical  tests  included:  b i l i r u b i n ,  calcium,  lactate  complete  -  laboratory  These  dehydrogenase  total  and  high  f e r r i t i n ,  hematology  hematocrit,  morphology.  conclusion  of  to  the  subjective  changes  They  also  were  exercise  S t a t i s t i c a l A l l analyzed over  speed,  analytical  profile  leukocyte  tests  were  and  count,  performed  techniques.  Compliance  At  of  each  variables  triglycerides,  hemoglobin,  c e l l  at  torque.  cholesterol  (HbAlc).  including  peak  phosphatase,  (HDL),  hemoglobin  two  glucose,  albumin,  lipoprotein  platelet  periods.  alkaline  protein,  at  performed  the  hematological  testing  acid,  out  themselves with o -1 speeds, 30 .sec  Monitoring  uric  obtained,  using  and  familiarized  were  considered  creatinine,  glycosylated was  repetitions  Hematological  the  had  carried  nitrogen,  total  density  was  result  Biochemical during  subjects  testing  and  Biochemical  the  that  had  questioned alterations  study  the  blindness  occurred regarding in  diet.  into  the  of  subjects the  during any  were  protocol  the  changes  two in  given and  time  a any  periods.  their  volume  Analysis  data  was  using  design  treatment  or  assess  the  was  test  entered  B.M.D.  s t a t i s t i c a l  collapsed variables  to for  allow a l l  12  U.B.C.  mainframe  software  packages.  comparison subjects  of  computer The  the  pre  (Figure  2).  and  and  crosspost  FIGURE  2:  DATA  ANALYSIS  TIME  PRE TREATMENT  GROUP  1  GROUP  2  <—  PLACEBO  Multivariate used  to  assess  strength The  and  acute  using was  body  by The  the  subjects  labelled basis  two  body by  analyses  and  body  variance. in  one  The  in  over  the to  way  with the  for  weeks  7  AA  and  P  of  and  analysis  variance  of  were  between  to  AA  stimulation  greatest  difference  response and  study  of  P  with  two and  V02max  level  -9-  for in  data  repeated order  to  responses  of  using  over  also the  repeated  was  and  AA. as  difference  then  compared way  compared study  was  AA  were  on  the  analysis  of  for  changes  period  measures.  significance  to  c l a s s i f i e d  net  one  calculated  response  were  were  were  for  their  least  groups  groups  variance  from  the  performance  the  compared  fitness.  the  composition  were  hematological  hormonal  to  subjects  composition,  calculated  the  was  administration.  Biochemical  and  The  body AA  >  measures  ingestion  response  4  PLACEBO  repeat  subjects'  GH  analysis the  the  s e n s i t i v i t y  their  two  variance  in  strength  composition two  of  coefficients  non-responders.  of  >  relationships  subjects'  responders,  AA  analysis.  Correlation  subtracting 4  > <  responses  using  composition, The  > <—  performance  analyzed  determine  AA  changes  multivariate  measures.  <  analysis  hormonal  POST rp T R E A MENT  set  using For  at  a a l l  0.05.  RESULTS Subjects The 41),  s u b j e c t s had  with  k.g..  an  average  were  recreational  involved  activities  time.  weight  suffered  a fractured  and  one  clavicle  listed  growth  km  weight 51.2  not  through  intensity  subjects  79.1  ml/kg/min), Several  alter  basis,  rowed o n c e a week.  p a r t way  of  p e r week.  but d i d  One  t h e AA  their  two  were  subject  period,  of c y c l i n g  and  until  d i d not r e p o r t  any  he major  activity.  in  hormone r e s p o n s e s w e r e h i g h l y  Table  administration. baseline)  1.  was  response  different  There  The  net  to  was post  significantly Although 20.2%,  GH  an i n c r e a s e  response  the  AA  an i n c r e a s e AA  was  period  i n GH  at  with  120  than  responders  (n=4)  are  post  minutes  AA -  Neither  significance.  time,  and  was  GH of The no  than at the b e g i n n i n g .  levels  greater  and  i n s e r u m GH  statistical  d i d not vary  of the t e s t  (GH  variable,  than f o r placebo.  however, reached  a t t h e end  There  was  g r e a t e r f o x t h e AA  these d i f f e r e n c e s ,  response  max  on a r e g u l a r  an e q u a l d u r a t i o n and  or  and  23  Responses  The  vs.  cycled  a b l e t o resume r u n n i n g . The  Hormonal  GH  One  lifters,  changes i n d i e t  cm.  f i t ( a v e r a g e V02  other a c t i v i t i e s ,  regular  substituted  o f 30.08 y e a r s ( r a n g e  r u n n e r s a v e r a g i n g 23.8  in  over  age  h e i g h t o f 180.2  They w e r e m o d e r a t e l y  regular  was  an a v e r a g e  after  that  post  exercise. P,  but  The not  different. t h e AA  p = 0 . 5 2 ) , and  had  l o w e r body f a t  h i g h e r V02max ( 5 3 . 2  p=0.82) t h a n t h e n o n - r e s p o n d e r s -10-  (n=4),  v s . 51.8  (16.6%  ml/kg/min,  t h e s e d i f f e r e n c e s were  not  statistically responders'  significant.  RIA  bioactivity  Prolactin  Although was  fat  i n c r e a s e d (20.2%  statistically  The  no  from  The  n e t GH  by CT  scan  difference  response  study  w h i l e t h a t of  but  these  calculated  max:  following  was  the  differences  subtracting  AA  either  the  bioassay.  t h a n P,  there  two.  positively  p<0.05).  r=-.2582  by  negatively correlated  p < 0 . 0 5 ) , and  to  by  a c t i v i t y determined  (r=.6966,  no  significant  period (Table 2).  measured  by  CT  weighing. Thigh A e r o b i c and  factor  The  GH  t o %body  correlated response  (%body  fat  to  to P,  by  CT:  over  the  p>0.05).  girth  Anaerobic  changed  by  no  was  fatigue  sum  also  of  t h e r e was  no  skinfolds  and  anaerobic  performance  was  when  hydrostatic  lactate  difference  significantly  o f t h e Amino A c i d ( T a b l e 3 ) .  i n the maximal oxygen uptake  blood  unchanged  unchanged.  i i the a n a e r o b i c speed r a t e and  body f a t was  Fitness  the a d m i n i s t r a t i o n  difference  c h a n g e i n body c o m p o s i t i o n  Percentage  scanning,  N e i t h e r a e r o b i c nor  heart  the  Composition T h e r e was  was  was  between the  t o AA  unrelated  r = . 1 8 4 2 , p>0.05; V02 Body  o f t h e GH  (r=-0.6006,  was  period  significant.  oxygen uptake  however,  to 16.1%),  greater bioactivity  significant  treatment  to 21.8%),  t h e t o t a l GH  t h e r e was  maximal  the  body f a t d e c l i n e d ( 1 6 . 6 %  non-responders were n o t  During  test.  During  -11-  post  time  the endurance  rose s i g n i f i c a n t l y  b e t w e e n p r e and  or the  AA.  There  with time,  to run, but  Strength Administration measurement change The  d i d not  i n s t r e n g t h between t r a i n e d  s t r e n g t h , was Biochemical  of  distal  normal  and  range  ferritin,  changes  T h e r e was and  no  alter  as  any  differential  u n t r a i n e d muscle  musculature,  Hematological and  reflected  groups. by  grip  throughout  Al-C  Measures  hematological  cholesterol,  hemoglobin  significantly  unchanged.  Biochemical  the  data  study  H.D.L.  a l l remained w i t h i n  (Table  cholesterol,  were s p e c i f i c a l l y  analyzed,  5).  the  Hemoglobin,  triglycerides, and  no  and  significant  occurred.  Subjective There  Changes were  questionnaire. to t e l l  subjects receiving which  t h e AA  s t r e n g t h ( T a b l e 4).  of  strength  unable  of  the  increases  no Five  s u b j e c t i v e changes r e p o r t e d  subjects  n o t i c e d no  w h i c h compound was  thought P.  uniform  they  given  were r e c e i v i n g  F i v e s u b j e c t s were a b l e  active  drug  was  i n p e r f o r m a n c e and  taken. decreased  -12-  differences  on and  the were  d u r i n g which p e r i o d . AA  when t h e y  to i d e n t i f y They  were i n the  reported  fatigue after  Two fact  period  in  subjective workouts.  TABLE  FACTOR  0  GH  POST  GH  GH  NET  MIN.  (120  POST  MIN.  -  0)  EXERCISE  E X E R C I S E NET (Post ex. -  GH  HORMONAL  AMINO (mean  GH B A S E L I N E (ng/ml)  120  1:  120)  DRUG  LACTOGEN (ng/ml)  TOTAL  GH A C T I V E (lactogen  -  PRO)  0.3514  2.6 (± 2.0)  2.6 (± 2.3)  (±  0.84 (+ 2.0)  (+  16.6 (± 9 . 7 )  13.5 (+ 1 1 . 6 )  0.3911  14.1 (+ 1 0 . 5 )  11.7 (+ 1 0 . 5 )  0.5228  (+  POOLED  PLACEBO ( m e a n +_ S D )  1.7 (± 1.9)  POOLED  PROLACTIN (ng/ml)  ACID + SD)  RESPONSES  6.3 3.6)  1.8  0.2423  l.D  -0.73  (+  0.1359  1-5)  5.8 2.0)  0 . 5679  10.6 (± 3.5)  12.2 (± 4 . 5 )  0.2825  11.5 (± 5.5)  11.5 (+ 4 . 4 )  0.9575  0.85 (+ 4 . 3 )  -0.71 (+ 2.7)  0.2107  -13-  TABLE 2: ANTHROPOMETRIC DATA PRE (mean + SD)  FACTOR  POST (mean + SD)  HEIGHT (cm)  180.3 (± 3.7)  180.3 (+ 3.7)  WEIGHT ( k g )  78.5 (+ 7.6)  79.3 (± 7.9)  0.141  %FAT by CT  19.1 (± 7.3)  19.7 (± 7.8)  0.209  %FAT by  15.3 (+ 4.5)  15.5 (± 5.4)  0.705  SUM SKINFOLDS (mm)  83.0 (+ 2 5 . 7 )  87.9 (+ 2 9 . 3 )  0.082  THIGH GIRTH (cm)  59.6 (+ 4.5)  60.3 (± 4.5)  0. 107  U/WW  -14-  TABLE  FACTOR  V02  AST  PRE (mean +  MAX  (ml/kg)  TIME  HEART  PERFORMANCE  SD)  51.2 (± 5 . 6 )  (sec) (±  ENDURANCE  3:  50.5  48.0 H.7)  (±  7.8)  (+  50.2 13.4)  SD)  0.503  0.251  RUN  RATE:  10  MIN  164.6  (± 20  MIN  30  0  MIN  (+  MIN  20  MIN  30  11-9)  169.3 (+ 1 2 . 9 )  MIN  10  (+  165.5 10.5)  (+  167.8 11.6)  (+  171.5 11.8)  165.6 (±  LACTATE (mmol/ml)  POST (mean +  1 .33 0.76)  (+  3.35 (+ 0 . 8 9 )  3.48 (+ 2 . 1 6 )  3.55 2.20)  (+  (+  3.27 2.11)  2.61 (+ 1.13)  -15-  H.R. vs. Pre/Post p=0.534  0.53 0.16)  (+  MIN  H.R. vs Time p=0.0005  3.01 1.97)  L a c t a t e v s . Time p=0.0015  Lactate vs. Pre/Post p=0.3614  TABLE 4: STRENGTH FACTOR  PRE (mean + SD)  POST (mean + SD)  GRIP  58.9 (± 5.8)  (+  RT. QUADRICEPS (ft.lbs at 30 d e g r e e s / s e c )  128.3 (+ 21 .9)  125.4 (+ 2 4 . 6 )  0.6126  RT. QUADRICEPS (foot.lbs at 180 d e g r e e s / s e c )  64.2 ( + 17.5)  65.9 (± 1 5 . 4 )  0.7427  RT. HAMSTRINGS (foot.lbs at 30 d e g r e e s / s e c )  50.7 (+ 1 4 . 4 )  48.7 (+ 1 4 . 4 )  0.3069  RT. HAMSTRINGS (foot.lbs at 180 d e g r e e s / s e c )  26.3 (+ 8.3)  28.2 (+ 7.5)  0.3112  -16-  60.4 6.6)  0.192  TABLE 5: HEMATOLOGY / BIOCHEMICAL FACTOR  PRE (mean + SD)  POST (mean + SD)  HEMOGLOBIN  15.1 (± 0.9)  15.1 (+ 0.8)  0.9156  FERRITIN (ng/ml)  135.0 (+ 5 6 . 6 )  126.8 (+ 4 6 . 8 )  0.4598  CHOLESTEROL  176.8 (+ 3 2 . 2 )  172.7 (+ 2 6 . 8 )  0.5622  HDL CHOLESTEROL (mg/dl)  48.8 (+ 9.1)  47.1 (+ 1 0 . 7 )  0.6505  CHOL : HDL RATIO  3.68 (+ 0.64)  3.79 (+ 0.91)  0.5362  TRIGLYCERIDES (mg/dl)  82.7 (± 3 9 . 6 )  83.6 (+ 3 7 . 9 )  0.9197  HEMOGLOBIN A l e (% o f t o t a l )  4.73 (+ 0.40)  4.72 (+ 0.38)  0.9182  (gm/dl)  (mg/dl)  -17-  DISCUSSION The  control  o f GH  secretion  fully  understood.  under  hypothalamic c o n t r o l .  via  two  (GHRH)  releasing  GH  G r o w t h hormone i s r e l e a s e d  and  one  are i n f l u e n c e d  release  by  amino a c i d s ,  thought  that  mediated  through c h o l i n e r g i c  the  mediated  It  secretion large  of  is  amino  different  releasing The  neurons,  serotoninergic,  as t h e b l o c k a d e  of other s t i m u l i  Other  levels that  exercise  as a t r o p i n e w i l l  t h e h i g h e r GH  and  and  hormones levels  during  in  the  serum It  are  is both  b l o c k the  influence  GH  females,  menstrual  the u l t i m a t e  d e p e n d e n t on  such  and  neurotransmitters.  of  control  and cycle  of  the balance  GH  of  a  are  a  influences. s t u d i e s have d e m o n s t r a t e d  as a t e s t acids  is  (GHIF).  changes i n temperature  (16).  those  release  an i n t r a v e n o u s i n f u s i o n used  effects  these  thus apparent  p o t e n t s t i m u l u s t o GH  is  by  as w e l l  of a r g i n i n e  multifactorial  number o f  GH  by h y p o t h a l a m i c  adrenergic,  neurons,  to both s t i m u l i  is  Pre v i o u s  to  through  as d e m o n s t r a t e d  (17,18).  The  the i n f l u e n c e s  fluctuation  pituitary  regulation  somatostatin  stimuli,  and  are  levels  alpha  (15).  glucose  response  pituitary  the  stimulatory,  controlled  cholinergic  beta a d r e n e r g i c s t i m u l i  GH  one  from  i s not  by a number o f d i f f e r e n t n e u r o t r a n s m i t t e r s .  i s increased  exercise,  direct  inhibitory,  f a c t o r s are i n turn  d o p a m i n e r g i c , and  as  The  h y p o t h a l a m i c hormones,  hormone  which  i s a complex p r o c e s s t h a t  (2,3,16,17,20),  o f 30  of p i t u i t a r y  can  response  also  t h a t amino a c i d s  response  Oral administration  s e r u m GH,  patterns reported in  d o s e s o f a r g i n i n e a s p a r t a t e ( 2 5 0 - 5 0 0 mg/kg: -18-  t h e GH  grams o f s r g i n i n e h y d r o c h l o r i d e  function.  increase  and  and the  there  are  literature.  17.5-35 gms  of two High  for a  70  kg  adult) w i l l  ng/ml ( 3 , 1 9 ) . for  a 70  kg  a d u l t ) h a v e no  times  average  60%  700%  the  GH  The  Isidori  was did  h a v e no i n the  et  i n GH  and  1.2  in  gms  GH  levels  pilot  of  levels  study  a l (2),  ineffective  and  of 1.2  gms  d o s a g e s and  GH  side  the  effects limited  any  one  the  main study  found  the  the  sleep  but  an  increase  by  responses.  a pilot  study  combinations  of  single daily  amino of  arginine GH  and  a  assessed  results  The  arginine,  surge  cause  (2).  i n GH.  an  pyrrolidone  minutes  Unpleasant  amount o f AA  repeated  to  of  20 gms  cause  within subjects.  oral  -  r e l a t e d GH  arginine  combination  and  response The  study  that  higher  gastrointestinal  that could  t i m e t o l e s s t h a n 8 g r a m s . I t was using  doses  unable to d u p l i c a t e the  increased  doses produced higher  90  performed,  i n causing  was  low  12  mg/kg: 7  have been r e p o r t e d  h i g h l y v a r i a b l e b o t h b e t w e e n and show t h a t GH  to  (100  effect,  the  within  was  was  while  immediate  lysine  the main study  (20),  level  responses to v a r i o u s  acids.  lysine  day  effect  administration  increase Before  a  increase  Acute  carboxylate  immediate r i s e  Lower doses of a r g i n i n e a s p a r t a t e  several  (3).  c a u s e an  be  ingested  thus decided  to  d o s e o f 6 grams o f  at  conduct arginine  hydrochloride. The those the  GH  i n the  responses found pilot.  r e s p o n s e t o AA  levels  were  statistical subjects  variability  main s t u d y  G r o w t h hormone was being  highly  greater  study.  increased  however,  possibly  A second  i n r e s p o n s e t o AA,  were  similar  by  the  i n magnitude than that  variable,  significance,  i n the  i n the  due  and to the  did  AA,  with  t o P. not  The reach  s m a l l number  i n f l u e n c e i s the  of  inter-subject  a phenomenon t h a t had  -19-  to  been  noted  in  the  pilot  subjects, level  as  and  is  correlation  can i n f l u e n c e  supported  by  statistically  the  influenced  subject  who  the  a decrease  GH  The  response for  weighing, selection of  One  t o AA  indicator a  t o t h e AA. body  but  significant body f a t  somatotype  this  were  difference  indicate  that  of a response  these the  uptake  would  i s most  or endurance t r a i n i n g .  The  -20-  in  body  fat  consistently using  higher  hydrostatic  related  f o r the scan,  as t h e  (pre:  of  the h i g h e s t  likely  to a chronic  study such as t h i s ,  w h i l e t h e non-  t h e one w i t h  calculated  seem  t o have  by a l l t h r e e m e t h o d s  v a l u e s however, are l e s s  composition  not  that  oxygen  a decrease  had a h i g h c o r r e l a t i o n  The ab s o l u t e  and  were  I t i s of note  The CT s c a n showed  f a t than  This  administration.  as d e t e r m i n e d  o f t h e t h i g h as t h e s i t e  steady state  strength  fitness  c h a n g e i n body c o m p o s i t i o n o v e r t h e  net change i n a s s e s s i n g the r e s p o n s e Body  in  f a t and h i g h e s t  s u b j e c t i n q u e s t i o n was  t h e two m e t h o d s  r=0.94).  a  non-responders  s u b j e c t showed  the treatment period  values  of  may  the  (15,17).  f a t over the treatment p e r i o d ,  did not.  measurement.  as  o f AA a d m i n i s t r a t i o n . The r e s p o n d e r s t e n d e d  i n body  responders over  no s i g n i f i c a n t  of  t o AA and p e r c e n t a g e  results.  a l s o had t h e h i g h e s t GH r e s p o n s e  7 week p e r i o d  finding  but the t r e n d  the o v e r a l l  factors  responses  and  had t h e l o w e s t body  T h e r e was  such  The d i f f e r e n c e s  responders  significant,  factors  GH  response  oxygen uptake.  between  be due t o t h e s o m a t o t y p e  recognized that  b e t w e e n t h e GH  maximal  V02max  T h i s may  i t i s well  obesity  possibility  and  study.  to  the  results  r=0.89,  post:  important than the  t o AA. to  be  the  low l e v e l where  most  increase  sensitive i n GH, i n  t h e r e i s no c h a n g e  study r e s u l t s  indicate  in  that a  small  change  i n GH l e v e l s  composition. similar  to t h i s  nitrogen were  There  been no r e p o r t s o f any  o n e , h o w e v e r , an a n i m a l  balance  given  have  does n o t l e a d t o any c h a n g e  and n e t a n a b o l i c  study  effect  in  human  reported  studies  a positive  ( p < 0 . 0 1 ) when  l a r g e doses of a r g i n i n e a s p a r t a t e  (1,500  rabbits  mg/kg/day)  (21). Although  t h e i n v e s t i g a t o r s d i d n o t m e a s u r e GH l e v e l s  rabbits,  previous  GH  to  their that  arginine  work had d e m o n s t r a t e d  dose o f amino a c i d .  aspartate  Wistar  p e r day i n c r e a s e d  weight  o f 3 5 . 1 % c o m p a r e d t o an a v e r a g e w e i g h t i n c r e a s e control  and  administration  attempts  at  aspartate  were s p e c i f i c a l l y  training  through  three  times  of  heart  alone  aspartate  study  state  avoid  Several  a day ( 2 3 , 2 4 , 2 5 , 2 6 ) . A d o u b l e b l i n d  claimed  but r e p o r t e d  any  previous  rate recovery the r e s u l t s  i n oxygen  neither absolute  after  could  a  h a v e been due t o a  study  using  uptake  reported  standardized  in  (23).  values  bout  nor a of  training  4 grams o f a r g i n i n e  showed an i m p r o v e m e n t i n c a r d i o v a s c u l a r  -21-  control  i n c o n t r o l s (p<0.005)  an i n c r e a s e  in  arginine  i n maximal oxygen uptake  An u n c o n t r o l l e d s t u d y  (25). A double b l i n d  daily  levels.  to  the  a t h l e t e s h a v e shown i m p r o v e m e n t s  s i g n i f i c a n c e (24).  rapid  instructed  fitness  a 21.2% i n c r e a s e  double b l i n d  e x e r c i s e however, effect  26.2% i n  t h e a d m i n i s t r a t i o n o f 1.0 gram o f  treated subjects,  more  of only  of  average  The s u b j e c t s were i n a s t e a d y  s u b j e c t s , and a 6.5% i n c r e a s e  Another  levels  by an  p e r f o r m a n c e was n o t a f f e c t e d by  increasing their  demonstrated  treated  in  and  i n actively  performance  study  anaerobic  of a r g i n i n e .  exercise,  studies  mg/kg  animals ( 2 2 ) .  Aerobic  of  i n the  a large increase i n  r a t s f e d 500  their  body  fitness  as  assessed  conducted  by t h e M a r t i n e t  test  ( 2 6 ) . T h e s e e x p e r i m e n t s were a l l  in  actively training elite  fats  and h i g h  maximal oxygen u p t a k e s ,  have  higher  subject  GH r e s p o n s e s t o t h e amino a c i d .  changes i n the p r e s e n t  There  was no s i g n i f i c a n t  subjects.  had  The  test  high  inter  likely  to  The d i f f e r e n c e s  in  explain  the l a c k of  study.  increase  and i n t r a  i n strength  subject  in  the  variability  test  f o r the  w o u l d h a v e made s i g n i f i c a n c e u n l i k e l y e v e n i f  subjects  found  that  there  t r a i n i n g was s u b j e c t i v e l y  and  recovery  was i m p r o v e d d u r i n g  Two  subjects  thought  received  P.  period,  while  The  one  double  in  fatigue,  an in  subjects  (27),  being  related  while the  experienced  by t h e t r e a t m e n t  reported and those  rate  using  improvement i n r e c o v e r y well  improvement  were group.  of recovery  receiving  by  and Only  less  -22-  capacity with  objective are i n  general  18  of  and  general  s t a t e of  studies  as also  28  their those  Another double b l i n d  Other  In  a  than  f o r t h o s e on a r g i n i n e  placebo.  the P  aspartate.  improvements,  improvraents i n s l e e p i n g ,  they  r e l a t e d a decrease  time,  generally  AA.  regarded  arginine  on a r g i n i n e .  same  during  study however,  25 o f 30 s u b j e c t s  of  being,  responses are often  the European s t u d i e s  the  d e c r e a s e i n work  findings i n this  sensations  (23),  of  easier  the time  i f they are not supported  subjective  b l i n d study  improvement  found a s l i g h t  Subjective  especially  agreement w i t h  control  t h e y w e r e r e c e i v i n g AA d u r i n g  the other  t h e AA p e r i o d .  changes.  the a d m i n i s t r a t i o n  One o f t h e s e t h o u g h t he had more e n e r g y  skepticism,  with  body  been n e t i n c r e a s e s . Five  in  and were t h u s  s o m a t o t y p e and t r a i n i n g p r o g r a m s may  significant  Cybex  a t h l e t e s who had l o w  study well  compared report  subjective  improvements i n t r a i n i n g  Biochemical normal  range d u r i n g  study  may  acid  ingestion  similar low  not  GH  level  i s not  its  studies revealed tissues  course  other of  17  likely  of h i g h no  h o w e v e r was to  macroscopic  this  harmful  Although  no  conducted  suggests that  amino  in subjects  is  -23-  thus or  a  this lipid  was  done i n  i n the  urinary  arginine  aspartate  hospitalized patients, unclear.  arginine aspartate  or m i c r o s c o p i c  with  glucose  increases  on  the week  urinalysis  following oral  in a 7  b e e n p r e d i c t e d , and  Although  (22).  (24,25,26).  remained  seem t o a f f e c t  athletes  oral  arginine  study.  have r e p o r t e d  Ketosteroids  at autopsy  t o be  does not  authors  dose,  the  c h a n g e s had  i n GH  relationship  of  on  variables  terra e f f e c t s ,  or e r y t h r o p o e s i s .  (28). That study, and  the  p r e d i c t long  increase  study,  excretion  hematological  r e s p o n s e . No  metabolism this  and  while  Toxicological  i n r a t s and  abnormalaties  in  mice any  CONCLUSIONS The  daily  hydrochloride elevations runners.  i n this  a s a r e s u l t o f t h e AA i n g e s t i o n . in  group, One  subjective  response than o t h e r s . initial  subject  tended  however, suggest t h a t  and  subjective  cause  more r a p i d r e c o v e r y . who  may  administration It  increase  decreased  Previous  Moreover,  in  fat)  might  strength  amino a c i d studies acid  i n highly  studies  body  daily  arginine body  fatigue in  response high  and elite  to  (high  Active  have  The same  V02max,  AA  fitness  d o s e s o f AA w o u l d  population.  positive results.  conditioned  GH  could  can a l t e r  l o w body f a t and  population  Further  with  reduced  o r f i t n e s s might have changed  ingestion.  trend  A placebo e f f e c t  t o h a v e a GH  higher  a d i f f e r e n t subject have y i e l d e d  a  h i s body f a t a n d had a  these changes occurred  of t h e i r that  include  c a u s e d a GH r e s p o n s e and e f f e c t i n t h i s dose  some  m a x i m a l o x y g e n u p t a k e i n humans,  be more l i k e l y  i s possible  T h e r e was  AA a d m i n i s t r a t i o n  changes that  because  with  towards a change i n  improvement i n t r a i n i n g .  i n animals,  AA,  inter-  i n p a r t i c u l a r d e m o n s t r a t e d a marked  and he a l s o  composition  increase  GH  V02max and a l o w e r body f a t i n t h e  f o r a l l of these changes.  aspartate,  T h e r e were  t h e GH r e s p o n s e t o t h e  and t h e y a l s o  r e s p o n s e t o t h e AA,  levels.  d i d not cause s i g n i f i c a n t  s t r e n g t h or  composition.  athletes  arginine  T h e r e w e r e no c h a n g e s i n body c o m p o s i t i o n ,  both a higher  account  of  recreational  responding  strong  grams  f i t , male  a much g r e a t e r  towards  6.0  group o f m o d e r a t e l y  differences  having  of  o v e r a 7 week p e r i o d  performance subject  administration  low  AA body  training  to  the response  to  investigations, including training a t h l e t e s are necessary  i n g e s t i o n c a n be s a i d t o i n c r e a s e -24-  before  GH l e v e l s o r c a u s e  amino  changes  in  fitness  level,  performance  suggests  that  the o r a l  athletes  i s unlikely  o r body  ingestion  to cause  o f amino a c i d s  either  improvements.  -25-  composition.  harm  or  by  magic  This  study  recreational performance  KOSTYO, J . L . and REAGAN, C R . The Pharraac. T h e r . (1976) 2:591-604.  B i o l o g y o f G r o w t h Hormone  I S I D O R I , A., Lo MONACO, A. and CAPPA, M. A S t u d y o f G r o w t h Hormone R e l e a s e i n Man A f t e r O r a l A d m i n i s t r a t i o n o f Amino A c i d s . C u r r e n t M e d i c a l R e s e a r c h O p i n i o n s , (1981) 7:475-481. BESSET, A.,BONARDET, A., R0ND0UIN, G., DESCOMPS, B., and PASSOUANT, P.. I n c r e a s e i n S l e e p R e l a t e d GH and P r l . S e c r e t i o n a f t e r C h r o n i c A r g i n i n e A s p a r t a t e A d m i n i s t r a t i o n i n Man. A c t a . E n d o c r i n o l o g i c a , (1982) 99:18-23. BIGLAND, B. and J E H R I N G , B. M u s c l e P e r f o r m a n c e i n R a t s , N o r m a l , and T r e a t e d W i t h G r o w t h Hormone. J . P h y s i o l . , ( 1 9 5 2 ) , 116:129-136. APOSTOLAKIS, M., D E L I G I A N N I S , A. and MADENA-PYRGAKI, A. The E f f e c t s o f Human G r o w t h Hormone A d m i n i s t r a t i o n on t h e F u n c t i o n a l S t a t u s of Rat A t r o p h i e d M u s c l e F o l l o w i n g I m m o b i l i z a t i o n . The P h y s i o l o g i s t , ( 1 9 8 0 ) , 23(Suppl):SI11-112. P I C K E T T , J . B . , LAYZER, R.B., L E V I N , S.R., SCHNEIDER, V. CAMPBELL, M.J. and SUMNER, A . J . N e u r o m u s c u l a r c o m p l i c a t i o n s of A c r o m e g a l y . N e u r o l o g y , ( 1 9 7 5 ) , 2 5 : 6 3 8 - 6 4 5 . LEWIS, P.D.: Neuromuscular Involvement i n P i t u i t a r y G i g a n t i s m . B r i t i s h M e d i c a l J o u r n a l , ( 1 9 7 2 ) , 2:499-500. NAUGELSPAREN, M., T R I C K E Y , R., D A V I E S , M.J. and J E N K I N S , J . S . M u s c l e Changes i n A c r o m e g a l y . B r i t i s h M e d i c a l J o u r n a l , ( 1 9 7 6 ) , 2:914-915. WHITAKER, M.D., PRIOR, J . C , SCHUTHAUER, B., DOLMAN, L. , DURITY,F. and PUDECK, M. G o n a d o t r o p h i n - S e c r e t i n g P i t u i t a r y Tumor: R e p o r t and R e v i e w . C l i n i c a l E n d o c r i n o l o g y , ( 1 9 8 5 ) , 22:43-48. RENNIE, P.S., PRIOR, J . C , BRUCHOVSKY, N. and GOUT, P.W. B i o a c t i v e Form o f Serum L a c t o g e n : E f f e c t s o f T r e a t m e n t o f Prolactinoma P a t i e n t s With B r o m o c r i p t i n e . C l i n i c a l E n d o c r i n o l o g y , ( 1 9 8 5 ) , 22:65-73. GORDON, P., L i , D., M a c i n t y r e , J.G. and P r i o r , J . C . A s s e s s m e n t o f Body C o m p o s i t i o n U s i n g C o m p u t e r i z e d T o m o g r a p h y . M a n u s c r i p t P r e p a r a t i o n . (1986). S I R I , W.E. G r o s s C o m p o s i t i o n of the Body. I n : Advances i n B i o l o g i c a l and M e d i c a l P h y s i c s , Volume I V , ( 1 9 5 6 ) . Lawrence, J.H. and T o b i a s , C.A. ( E d i t o r s ) . Academic P r e s s , I n c . , New York.  -26-  13  VOLKOV, N . I . , SHIRKOVETS, E.A. and B O R I L K E V I C H , V.E. A s s e s s m e n t o f A e r o b i c and A n a e r o b i c C a p a c i t y o f A t h l e t e s i n T r e a d m i l l Running T e s t s . European J o u r n a l of A p p l i e d P h y s i o l o g y , ( 1 9 7 5 ) , 34:121-130.  14  CUNNINGHAM, D.A. and FAULKNER, J.A. The E f f e c t o f T r a i n i n g on A e r o b i c and A n a e r o b i c M e t a b o l i s m D u r i n g a S h o r t E x h a u s t i v e Run. M e d i c i n e and S c i e n c e i n S p o r t s and E x e r c i s e , (1969), l(2):65-69.  15  GALBO, H. H o r m o n a l and M e t a b o l i c A d a p t a t i o n s t o E x e r c i s e , ( 1 9 8 3 ) . G e o r g T h i e m e V e r l a g , New York.  16  CASANUEVA, F.F., VILLANUEVA, L., CABRANES, J.A., CABEZASCERRATO, J . , AND FERNANDEZ-CRUZ, A. C h o l i n e r g i c M e d i a t i o n of G r o w t h Hormone S e c r e t i o n E l i c i t e d by A r g i n i n e , C l o n i d i n e , and P h y s i c a l E x e r c i s e i n Man. J . C l i n . E n d o c r i n o l o g y and Metabolism, (1984), 59(3):526-530.  17  SHEPHARD, R . J . , AND SIDNEY, K.H. E f f e c t s o f P h y s i c a l E x e r c i s e on P l a s m a G r o w t h Hormone and C o r t i s o l L e v e l s i n Human S u b j e c t s . I n : E x e r c i s e and S p o r t S c i e n c e s R e v i e w s , ( 1 9 7 5 ) , J.H. W i l m o r e and J . F . K e o u g h , ( E d i t o r s ) . A c a d e m i c P r e s s , New York.  18  L I N F 0 0 T , J.A.: A c r o m e g a l y and G i a n t i s m . I n : E n d o c r i n e C o n t r o l o f G r o w t h , ( 1 9 8 1 ) . W.H. Daugheday ( E d i t o r ) . E l s e v i e r N o r t h H o l l a n d I n c . , New York.  19  E L S A I R , J . , POEY, J . , R 0 C H I C C I 0 L I , P., DENINE, R., MERAD, R. and BENOUNICHE, N. E f f e t s de L ' A d m i n i s t r a t i o n " P e r 0 s " a D o s e s V a r i a b l e s , D ' A s p a r t a t e D ' A r g i n i n e e t de C h l o r h y d r a t e D ' A r g i n i n e s u r l e s Taux D'Hormone de C r o i s s a n c e e t D ' A c i d e s G r a s L i b r e s du P l a s m a C h e z L ' E n f a n t N o r m a l a J e u n . P a t h o l o g i e B i o l o g i e , (1980), 28(10):639-644.  20  CAMPISTRON, G. A p p r o c h e P h a r m a c o l o g i q u e de L ' A r g i n i n e e t de L ' A c i d e A s p a r t i q u e . E t u d e P h a r m a c o c i e n e t i q u e e t P h a r m a c o d y n a m i q u e . T h e s i s No. 112, ( 1 9 8 0 ) , F a c u l t e des Sciences Pharmaceutiques, Toulose. c i t e d i n Besset et al.,op . c i t .  21  E L S A I R , J . , KHELFAT, M., TABET A0UL, M. and I K L E F , F. E f f e t s de L ' A s p a r t a t e D ' A r g i n i n e , A d m i n i s t r e ' p a r V o i e O r a l , S u r l e B i l a n D ' A z o t e du L a p i n N o r m a l ou T r a i t e p a r L'Hydrocortisone. Path. B i o l . , (1982), 30(4):206-210.  22  CASTAGNOU, R., E x p e r t i s e T o x i c o l o g i q u e de S a r g e n o r S o l u t e ' B u v a b l e , a 10% de L - A s p a r t a t e de L - A r g i n i n e . Med. I n t . , (1968), 3(11):811-817.  -27-  23  TRANCIOVEANU, M., DRAGAN, I . , PLOESTEANU, N. e t CORNEANU, I . E t u d e de L ' I n f l u e n c e du S a r g e n o r S u r l e s P r o c e s s u s de R e c u p e r a t i o n Chez l e s S p o r t i f s de P e r f o r m a n c e . C i n e s i o l o g i e , (1971), 10:137-145.  24  DRAGAN, I . , V A S I L I U , A. and LAZAR, N. R e s e a r c h e s C o n c e r n i n g t h e I n f l u e n c e o f " S a r g e n o r " on H i g h - P e r f o r m a n c e Sportsmen. Proceedings of t h e T h i r d European Congress of S p o r t s M e d i c i n e , B u d a p e s t , September, 1974.  25  L ' E G L I S E , M. U t i l i s a t i o n de L ' A s p a r t a t e de L ' A r g i n i n e c h e z 50 J e u n e s S p o r t i f ( E s p o i r s N a t i o n a u x ) . C i n e s i o l o g i e , ( 1 9 7 0 ) , 9:337-355.  26  S E L L I E R , J . I n t e r e t de L ' A s p a r t a t e D ' A r g i n i n e " S a r g e n o r " c h e z d e s A t h l e t e s de C o m p e t i t i o n en P e r i o d e D ' E n t r a i n e m e n t I n t e n s i f . R e v . Med. T o u l o u s e , ( 1 9 6 9 ) , 8 : 8 7 9 - 8 8 1 .  27  STREICHER, M., CHAURAND, J . , T I X I E R , P., DUBARRY, J . P . , B E R D E I L , S., BENECH, A. e t PONTAGNIER, H. E t u d e s B i o c h i m i q u e e t C l i n i q ^ u e de L ' A c t i o n de L ' A s p a r t a t e D ' A r g i n i n e s u r l e s R e a c t i o n s de F a t i g u e de 58 A t h l e t e s . C i n e s i o l o g i e , (1974), 13:342-373.  28  MARTIN, M.P., VINCENEUX, M. e t HATOY, M.D. E t u d e C l i n i q u e e t B i o l o g i q u e de L ' A s p a r t a t e D ' a r g i n i n e c h e z l e s S u j e t s de M o i n de 50 A n s . J . d e s Med. du N o r d e t de L ' E s t , ( 1 9 6 7 ) , 4:54-55.  -28-  APPENDIX A  LITERATURE REVIEW  -29-  GROWTH HORMONE: REVIEW OF  LITERATURE  1-GROWTH HORMONE 1-1 STRUCTURE AND PRODUCTION Human of  The a n t e r i o r  which  production  higher  i s i n f l u e n c e d by b o t h  composed  of about  21,500  o f 5 t o 10 mg o f GH,  age and s e x ,  cells (2). and has  been  a t b e t w e e n 0.4 a n d 1.0 rag p e r day i n a d u l t m a l e s ,  d u r i n g t h e day  ng/ml  rates,  is  weight  contains a total  rates i n adolescents  fluctuate 3.0  pituitary  a molecular  i s s y n t h e s i z e d and s t o r e d i n t h e s o m a t o t r o p h  estimated  and  (GH) i s a p o l y p e p t i d e hormone  191 a m i n o a c i d s , a n d h a v i n g  (1).  GH  g r o w t h hormone  and females  females  females  Levels  and a d o l e s c e n t s  taking estrogens  metabolized  Serum GH  levels  b u t a r e g e n e r a l l y i n t h e r a n g e o f 0.5 -  i n t h e a d u l t male ( 2 , 3 ) .  with  (2,3).  with  having  i n the l i v e r ,  having  still  reflect higher  higher  production  levels  levels  w i t h a plasma h a l f - l i f e  (2,4),  ( 4 ) . GH  o f 17 t o 45  minutes ( 5 ) . 1-2 CONTROL OF GH Growth  SECRETION  hormone  through  a feedback  growth  hormone  somatostatin. incompletely originates  release  system i n v o l v i n g  releasing Although  understood,  hormone  that  (GHRH),  nuclei  of the hypothalamus,  hypothalamic  o f GHRH i s m a i n l y  receptor  controlled  two h o r m o n e s , one e x c i t a t o r y ,  i t i s thought  from t h e a n t e r i o r  to  i s  and  one  inhibitory,  t h e r e l e a s e mechanisms a r e complex  while  attaches  from t h e p i t u i t a r y  sites  that somatostatin  control  periventricular  system,  from t h e v e n t r o m e d i a l  and t h e l i m b i c on t h e GH -30-  and  system  secretory  and  arcuate  (6,7,8). granules  GHRH and  stimulates  GH r e l e a s e  Somatostatin release the may  acts  t h r o u g h a c t i v a t i o n o f membrane  at a separate  i n a non-competitive  pituitary diminish  receptor  fashion  t o GHRH i s i n f l u e n c e d  with  site  (8,9).  and  cAMP ( 8 ) . inhibits  GH  The s e n s i t i v i t y  of  by a number o f f a c t o r s ,  and  age ( 7 , 8 ) .  1-3 GH RELEASE There release, mediated  a r e many p h y s i o l o g i c with  on a s p e c i f i c  and s e r o t o n e r g i c  neurons  i n t e r a c t i o n between t h e s t i m u l i ,  each other  area of the  (6,7). with  combinations  basal  during  t h e m e n s t r u a l c y c l e and h a v e a g r e a t e r  basis  of  stimuli estrogen  brain  levels,  as  and  (6,7).  a s women h a v e levels  responsiveness  are probably  responses  deal  modulating  d e m o n s t r a t e f l u c t u a t i o n s i n GH  ( 5 ) . These d i f f e r e n c e s  GH  adrenergic,  manner  on GH r e s p o n s e ,  higher  release  GH l e v e l s ,  to  There i s a great  i n e i t h e r a s y n e r g i s t i c or competitive  There a r e hormonal i n f l u e n c e s  GH  stimuli  t h r o u g h p a t h w a y s c o n t r o l l e d by d o p a m i n e r g i c ,  cholinergic of  each a c t i n g  and p h a r m a c o l o g i c  are  to  on  the  decreased  in  m e n o p a u s a l women, a n d t h e r e s p o n s e s o f men t r e a t e d  with  are  women  (5,10).  release,  as i t s  s i m i l a r t o , but s l i g h t l y  Testosterone  does  administration in  their  beginning related by  are  seem t o i n f l u e n c e  to arginine  episodic  occurring  of  GH  the  60 t o 90 m i n u t e s a f t e r s l e e p  neurons  day,  with  onset,  (2,3,7,11). I t i s thought  GH s u r g e s a r e i n i t i a t e d  change  infusion (10).  GH s u r g e s d u r i n g  o f s l o w wave s l e e p  serotonergic  those  t o 8 women d i d n o t r e s u l t i n a s i g n i f i c a n t  GH r e s p o n s e  There largest  not  l e s s than  estrogens  the  at the  that  sleep  by t h e l i m b i c s y s t e m and m e d i a t e d  (6,7), -31-  and t h a t  they  are decreased  in  magnitude  i n both the e l d e r l y  secretion  of  increased  GH  may  activity  secretion of  increased GH  is  physical  release  i t i s possible  increased  that  rising  The  blood  g l u c o s e even i n the p r e s e n c e to hypoglycemia  neurons  at  of normal  i s mediated  the l e v e l  induced  pituitary  function,  of n o r m a l  individuals  of  response  L-Dopa ( 1 4 ) .  (type,  a  intensity  individual  (age,  through  results  a t 75 in  interactions  between  decrease i n (3,13).  through  alpha nucleus  i s e m p l o y e d as  i n a GH  and  serotonin antagonists  rise  i n 85  t o 90%  GH  a  test  t o 100  GH  response  and  induced to  i s influenced  duration), body  release,  o f V02max r e s u l t i n g  magnitude to that  sex,  factors,  a rapid  is  of  percent  (11).  and  environmental  and  response  serum l e v e l s  g r e a t e r than the responses The  GH  ventromedial  potent stimulus f o r  equivalent and  centre  beta a d r e n e r g i c blockade  hypoglycemia  and  exercise  hypoglycemia and  is  by  the  by a l p h a a d r e n e r g i c b l o c k a d e and  minutes  increased  of  decreased  Exercise  acts  GH  hypoglycemia  i n part  and  Insulin  c a n be  and  (6,7,11),  (11).  with  increase  i t  glucose.  by b o t h a b s o l u t e h y p o g l y c e m i a ,  adrenergic  can  to  stimulated  response  athletes  i n response  by  The  trained  stresses  inhibited  blood  nocturnal  catecholamine release (1). is  a  The  A l t h o u g h t h e e x a c t m e c h a n i s m and  unknown,  central  in  (2,11).  (12).  and  (1,2,3,5,6,7).  control  obese  be i n c r e a s e d  levels  Psychological  and  the  composition,  -32-  and  GH  have  in  a  20 GH  insulin  sleep,  arginine  by  exercise  the  characteristics  pre-treatment with  exercise  by  with  fitness  of  level),  v a r i o u s drugs. been  the  The  extensively  studied,  and  the  results  are  summarized  in  review  articles  (5,15). The  central  release  have not  control  been d e f i n i t e l y  adrenergic,  serotonergic,  inhibits  release  GH  adrenergic acts  blockade  the  increase  are  found  15  longer  (5),  d u r a t i o n GH  although  immediately The  of  exercise  response  than  although  the  rates,  blood  16  levels were  t o 23  may  found km  (20),  t o be  elevated  ultramarathon  Arm  work has  leg arm  work was  pressure,  and  In  exercise  then  decline  in  7  subjects  (19).  total  the  levels  GH than  amount o f work  been shown t o c a u s e a equivalent  of  levels  (14,18),  higher  also associated  and  onset  i n determining  producing  work a t an  probably  Peak  (5,18).  a peak and  e v e n when t h e  the  (5).  reach  beta  (17).  exercise  minutes  alpha  by  which  with  exercise  following  intermittant  (21,22).  exercise,  GH  neurons  i s increased  infusion,  exercise i s important  with  continuous  of  f o l l o w i n g a 100  response,  equal  they  type  during  minutes  decrease with a h a l f - l i f e of  B l o c k a d e of  c e n t r a l dopaminergic a c t i v i t y  w i t h more i n t e n s e  t o 30  related  dopaminergic  release  pyridoxine  increase  earlier  exercise  established.  while  ( 1 5 ) , and  levels  of  c h o l i n e r g i c and  (15,16),  through increased Serum GH  mechanisms  greater  is GH  oxygen  uptake  (23),  with  higher  heart  plasma n o r e p i n e p h e r i n e  and  lactate  levels. In  cycle  proportional changes that  the  decreased  ergometry, to  i n blood GH  the pH  GH  release  intensity and  of  l a c t a t e (24).  response i s greatest  towards basal  the  levels  with  has  been  work and  to  be  independant  of  Other authors moderate  i n maximal e x e r c i s e  -33-  shown  have  exercise, (25,26).  found and Still  other  authors  exercise One  intensity  failed  climbing,  m.p.h.)  for  walking load,  GH  total  release  the  subject's  in  unfit  between  a  the  load  fitness  level,  significant  found  induced  protocol  GH  a greater  may  psychological  Body c o m p o s i t i o n  (25,26).  protocol  of  t o be d e t e r m i n e d  to  the  studies  response shown  of e x e r c i s e  is  were  not  however,  have  response to  exercise  towards  basal  (25,26).  although  s t r e s s response  (30),  have  differences  responses to e x e r c i s e ,  be due t o l o w e r  i n response  to the  Other authors,  exercise  workloads  exhaustion  intensity  by  demonstrated  no d i f f e r e n c e  c h a n g e i n t h e GH  -34-  GH  response  training  although  influences  high a  even a t e q u i v a l e n t  in exercise  (5),  (28). A  repetition  (4  with  produced  stress contributed  intense  estrogen l e v e l s  the increase  higher  occurred  h a s been shown t o r e d u c e t h e d e c l i n e during  intense  a t moderate speed  i s thought  Longitudinal  training,  Women h a v e h i g h e r  that  that  (27).  had no e f f e c t ( 2 9 ) .  GH r e s p o n s e t o an e q u i v a l e n t  Training  of  subjects  exercise.  no t r a i n i n g  basis  with  bout of  response  high  and d u r a t i o n  i t i s possible  statistically  levels  load,  following exercise  following  (31).  low  between  response  a protein drink  s t u d y , however, demonstrated  to e x h a u s t i v e  noted  a l t h o u g h a GH  weight . l i f t i n g  f i t and u n f i t  although  lower  hours,  than i n f i t i n d i v i d u a l s ,  One  that  1.5  while  equivalent  relationship  b u t no r e s p o n s e t o w a l k i n g  repetition  increase,  any  response to a short  following pre-treatment with low  (15).  t o show  and t h e m a g n i t u d e o f t h e GH  a u t h o r d e m o n s t r a t e d a GH  stair  GH  have  possibly  i t h a s been  fitness  levels  on t h e  postulated (5),  or  a  to e x e r c i s e ( 1 5 ) .  t h e GH r e s p o n s e t o a v a r i e t y  of  stimuli,  including  responsive  cold and in  increases  s e c r e t i o n , as e x e r c i s e  result  in  a greater  (32,33,34). claim  GH  that  during  response  authors,  r e s u l t i n g from  Cold  ambient  i s a great  GH  although  GH  was  recovery  period  mechanism are  of  the  may  (5),  generalized  this  moderate  or  responses  than normal  other  intense  release hormones  neurotransmitter noradrenalin, apomorphine, inhibited  may  during in  exercise  than (34).  virtually  complete  exercise  (33,34),  to  during  the  merely  reflect  responses  stress  decrease be  post  exercise a  delayed  to temperature  reaction  (15).  (32),  by  drugs which  amines. clonidine,  response  GH  and  may this  subjects  alter is  -35-  exercise  have  than  in  higher  GH  bouts  agents  (5,35). including  the l e v e l s of the c e n t r a l  released  in  response  bromocriptine,  glucagon,  isoproterenol,  to  mild  exercise  pharmacologic  L-dopa, and  in  Diabetics  c o n t r o l s to s i m i l a r  i s influenced and  t h e GH  more p r o n o u n c e d  exercise  vasopressin by  i n magnitude  of  heated.  ingestion will  although  GH  t h e GH  i n the absence  be e s p e c i a l l y i m p o r t a n t i n s t u d i e s where  artificially Glucose  may  the  variability  increases  to i n c r e a s e  in  of i n t e r - s u b j e c t  surge greater  which  been shown t o  phenomenon,  s e c r e t i o n i n response  (33),  has  to  this  have r e s u l t e d  response. I t i s possible that part  less  be a s t i m u l u s  t h a n t h e same e x e r c i s e  deal  temperature  found  may  (20). Heating alone,  conditions  of  exercise  however, d i s p u t e  r e s u l t e d i n a GH  that  be  obese i n d i v i d u a l s being  i n a warm e n v i r o n m e n t  to heating  has  inhibition  GH  Other  there  responses  exercise,  with  (2,6,11,15).  Temperature GH  exercise,  while  phentolaraine,  its  to  propranolol, release  is  raethysergide,  cyproheptadine,  morphine,  glucocorticoids Amino  and  c a n s t i m u l a t e GH r e l e a s e .  drinks  (2,6,7,10,11),  (Bovril)  Serum GH was i n c r e a s e d  ingestion  o f 1.2 gm o f 1 - a r g i n i n e  of  (36).  1-lysine No  hydrochloride  (11,28),  seven-fold  fitness  and d e g r e e o f m a t u r i t y  Five  males  aspartate  aged  to  35  ingested  doses,  other  result The  resulting  rag/kg)  (37).  response endorphins  mg/kg  i n a 60%  (11). estrogen  (10), increased  composition,  the  authors.  of  arginine  increase  low dose acute  in with of GH  GH r e s p o n s e ( 3 8 ) .  GH r e l e a s e  i s u n c l e a r , but involved.  by t h e i n f u s i o n  free fatty  responses occur  The  of  beta  carbohydrate  diet  acids  (11),  and  i n b o t h men and women  a d m i n i s t r a t i o n (10,11,28).  -36-  acids  d o s e s ( 2 5 0 mg/kg)  a d m i n i s t r a t i o n of a high  Increased  amino  d o e s n o t s t i m u l a t e an  a r g i n i n e c a n be d e c r e a s e d  (39), prior  years  control,  this  s t u d i e s h a v e shown t h a t h i g h e r  hyperglycemia  clomiphene  by  ( 1 1 ) and c h o l i n e r g i c ( 1 6 ) n e u r o n s a r e to  20  body  Although  mechanism o f a r g i n i n e i n d u c e d  and 1.2  c a n a l l i n f l u e n c e t h e GH  250  i n an i m m e d i a t e , s i g n i f i c a n t  adrenergic  following  (83  of p i t u i t a r y  15 t o  GH s e c r e t i o n a s c o m p a r e d t o p l a c e b o  aspartate  response,  (6),  20  the subjects'  factors are reported  c h a n g e i n d a y t i m e GH v a l u e s  arginine  will  these  i n 3 divided  sleep-related no  of  Although  intravenous  90 m i n u t e s a f t e r t h e  when e i t h e r o f t h e  alone.  none  via  (36,37)  pyrrolidone carboxylate  were a d m i n i s t e r e d levels,  and  i n 15 m a l e s a g e d  r e s p o n s e was o b t a i n e d  response,  and  effective  amino a c i d s  w h i c h c a n be u s e d a s a t e s t  function.  gm  They a r e  through the i n g e s t i o n of simple  protein rich  infusion  imipramine  (2,6,7,11).  acids  both o r a l l y ,  chlorpromazine,  Dopamine  infusion  has  a dual effect  response  i f arginine  infusion, longer  on a r g i n i n e  i s given coincidently  but b l u n t i n g  period  i n d u c e d GH r e l e a s e ,  the response  i n c r e a s i n g the  and  i f arginine  early  i n the  i s given after  a  of i n f u s i o n ( 4 0 ) .  2-EFFECTS 2-1 FUNCTION The  most  important function  growth.  Administration  positive  n i t r o g e n b a l a n c e and a s t i m u l a t i o n  tissue  growth  regulation  to  o f GH i s t o  hypopituitary  ( 2 ) . Although  of l i n e a r  growth  it  i s now a p p a r e n t  that  day  t o day h o m e o s t a t i c  i t was  increase  children  results  of s k e l e t a l  once  somatic  thought  are  a  and  soft  that  the  i n c h i l d h o o d was i t s s o l e  i t s metabolic effects  in  function,  important  in  functioning.  2-2 METABOLIC GH  reduces  oxidative  metabolism  perhaps  in  (2,41,42). increase initial and (2). anti from  glucose  order  In  to  GH  and i s t h o u g h t inhibits  'nsulin the  release  from  release  is  of glucose  i s minimal  uptake  of  fatty  pathways immediate  (2,41),  however, intact  clinical  this  animals  significance  o f g l u c o s e and h a s  a  net  glucose i s l i b e r a t e d  g l u c o n e o g e n e s i s as w e l l  both i n response  acids,  an  In addition,  -37-  shifting  anabolic  i n normal,  the increased hepatic glycogen increased,  by  induces  t o be o f l i t t l e  (1,2,6,41).  through  for  a n i m a l s , GH  the c e l l u l a r  effect  liver  protein  uptake  effect  metabolism  the u t i l i z a t i o n  spare  hypopituitary  insulin-like  protein  towards  i n the c e l l u l a r  humans  and  stores  to  as  a  greater  (41).  Insulin  hyperglycemia,  and  through  a direct  increases  effect  insulin  on t h e b e t a c e l l s  levels  (2,6,41,42). T o t a l d a i l y by  GH  (42),  utilization  and  i t  levels  o f GH,  insulin has  of i n s u l i n  by t h e enzyme s y s t e m s  independant  of the  of i t s e f f e c t  production  been  pancreas on  glucose  i s markedly  proposed  that  for protein synthesis  increased  the  i s t h r o u g h enhanced a f f i n i t y (42).  that  increased  for  insulin  Prolonged  s u c h as t h o s e f o u n d i n a c r o m e g a l y ,  high  can r e s u l t i n  diabetes. GH  stimulates  tissue,  and  increases  respiratory to  a  quotient  reduction  hepatic  the  fat  mobilization  their  oxidation,  (1,2,6,41,42,43).  of p e r i p h e r a l a d i p o s e  s t o r e s and  of  increased  lipids  with  plasma  i n t h e m o b i l i z a t i o n o f FFA  however, t h e r e ( 4 5 ) . Because  was  normal  FFA  mobilization. GH  rats,  levels  exercise  has  possible  that  other  will  GH  demonstrated  response  This  during  levels  acts  synthesis  be d i s c u s s e d  with  animals (41).  i n t h e s e c t i o n on -38-  exercise (44), exercise  i n normal  rats, rats  had  no  role  i n the  known,  and  levels.  as  severe It is  glucocorticoids  and  response (41).  i s greatly increased  to hypophysectomized  a  h a v e been e r r o n e o u s  t h e e x e r c i s e were n o t  t h e FFA  plays  were g r e a t l y r e d u c e d i n  i n t e r p r e t a t i o n may  i n conjunction  in (FFA)  i n hypophysectomized  p r e v i o u s l y been shown t o d e c r e a s e GH GH  leads  acids  Following  t h e a u t h o r s c o n c l u d e d t h a t GH  hormones t o m e d i a t e Protein  of  s u c h FFA  t h e p o s t e x e r c i s e GH  the  the  i t s importance.  m o b i l i z a t i o n was no  during  in  increase  some s t u d i e s i n d i c a t e t h a t GH  investigators question  60 m i n u t e s , FFA  an  free fatty  significant  for  a resultant f a l l  stores,  Although  other  adipose  A d m i n i s t r a t i o n o f GH  (2,6,41,42,43). role  from  by t h e a d m i n i s t r a t i o n The  the e f f e c t  exact o f GH  mechanisms on  muscle.  2-3 GROWTH Somatic although Early in  there  i s increased  i s some c o n t r o v e r s y  through  i t was  only  growth occurred  the a d d i t i o n  liver  (46). at  (2,41,46).  The  Somatomedin levels  individuals  They  speculate  culture  medium,  levels the  that  i s o l a t e d the somatomedins, that  are synthesized  following  exposure  C,  also  to  are r e l a t i v e l y age o f 6 Levels  the catabolism  (47).  postnatal  somatomedins, higher The  GH  in  stimulating  period  with  years,  called  insulin-  low  in  and  infants,  decline  l e v e l s (46,47).  of aging  reach  in  Some  r e s u l t s from a  growth i s independant of  gradually  and i t i s s p e c u l a t e d  vitro DNA,  increasing  dependance  (47,48). Estrogens i n h i b i t  l e v e l s found effects RNA,  older  that  this  hour  authors reduction i n GH  GH  and  through  the production  of  feedback r e s u l t s i n  i n females ( 4 6 ) . of  somatomedins  and p r o t e i n  synthesis,  are  chondrogenic,  and i n c r e a s i n g  incorporation  of s u l f a t e i n t o p r o t e o g l y c a n s  (46).  insulin  effects,  uptake of g l u c o s e  like  GH  powerful  a r e more d e p e n d a n t on t h e 24  Intrauterine  levels,  in  t h e most  s o m a t o m e d i n l e v e l s i n r e s p o n s e t o an age r e l a t e d d e c l i n e  somatomedin  the  growth  (46,47).  l e v e l s t h a n peak GH  that  secretion  the  later  Somatomedin  1 (IGF-1)  by  GH  GH,  mechanism.  chondrocyte  to the c e l l  polypeptides  being  (46,47).  integrated  in  exact  s o m a t o m e d i n s h a v e been p u r i f i e d , w i t h  growth f a c t o r  adult  o f GH  and c i r c u l a t e i n t h e b l o o d  growth s t i m u l a t i o n  like  as t o t h e  of  a f t e r t h e y added serum from i n t a c t a n i m a l s  a group of growth promoting the  by t h e a d m i n i s t r a t i o n  i n v e s t i g a t o r s were u n a b l e t o s t i m u l a t e  vitro  and  growth  increasing -39-  cellular  They a l s o  the have and  amino a c i d s , a n d e n h a n c i n g The  i n vivo  separate  from  dependant, (48). and  GH,  (48).  o f GH i t s e l f ,  either directly  cell  sites  that  further  proliferation  to i s  on t h e p r e s e n c e o f GH  f o r both somatomedins ( 4 6 ) ,  h a s been shown t o d i r e c t l y  I t i sapparent  issue  as  or i n d i r e c t l y ,  has r e c e p t o r  which  synthesis (46).  e f f e c t s o f t h e somatomedins a r e d i f f i c u l t  those  Cartilage  g l y c o g e n and p r o t e i n  studies  stimulate  i t s  growth  a r e needed b e f o r e t h e  i s resolved.  2-4 MUSCLE Muscle both  growth  work  and  longitudinally occurring addition  number  of  myosin  and  factors  the linear  increase  The  troporaysin)  theZ lines  hormone mechanism  (50).  induced  with  grows  longitudinal  t h r o u g h an  proteins  both growth  through the  junction  (50,51).  increase  i n the  growth  (actin,  for fibre i n large  polyribosomes  a d j a c e n t t o e x i s t i n g m y o f i b r i l s . These  t o form  filaments  T h i s mechanism  at thec e l l u l a r  Muscle  rausculo-tendonous  are synthesized  growth,  i sa f u n c t i o n of  phase, i n c h i l d h o o d  i n diameter  myofibrils.  then aggregate  growth  at the  l i e i n the sarcoplasra  proteins  (49,50).  and c i r c u m f e r e n t i a l l y ,  of sarcomeres cells  to  hormonal  during  Muscle  that  i sa complicated process that  which a t t a c h  i s common  themselves  t o b o t h work  and  even  though  the underlying  control  level  appears  t o be d i f f e r e n t f o r t h e  two t y p e s o f g r o w t h . In  both types o f growth  t h e f o r m a t i o n o f new  many  requirements at a c e l l u l a r  must  be p r o d u c e d  RNA  polymerase.-  level  f r o m t h e n u c l e a r DNA, The  mRNA  appears -40-  (52).  proteins  The mRNA  template  a reaction catalyzed  i n the cytoplasm  has  by  where i t  attaches  to  carrying  the  final of  r i b o s o r a e s and specific  p r o t e i n . The  amino a c i d s ,  activity  of  When  increased  rate  then  addition  the  for  more  few  for several o f an  that  new  through  (41,53). hours  RNA  results  and  w i t h i n 24  muscles  if  initial  remains  results  GH  and  is  t o two  The  There  treatment  hours.  refractory  protein  by  detectable  l a g phase t h e r e  inhibitor  to  most  likely  of  of  its  protein  ability i s an  -41-  of  inhibited increased  additional time  GH, (54).  the  synthesis  translation  of  existing  attachment but  not  to  until  to hypophysectomized number and  size  of  ribosomes 18  increase  i n the  for 7  DNA  days  to  rats  24  (41).  ribosomes,  of m u s c l e to s y n t h e s i z e  i s continued  (41).  of  does i n c r e a s e ,  i n the  The  independant  f o r a much l o n g e r  i s a l s o independant  the  (53,54).  inhibitors  s u b s e q u e n t t o and  from enhanced  increase  hours the  (41).  no  (41,53),  i s administered  i n an  is  hours  remains e l e v a t e d  facilitation  GH  This  doubled  there  t h e n becomes r e f r a c t o r y t o  synthesis  after  supply  presence  amino a c i d u p t a k e i s o n l y  protein synthesis and  the  o c c u r r i n g e v e n when u p t a k e i s  r a t e of  h o u r s and  RNA,  mRNA  and  the  the  i t requires a transport protein  i s increased  the  synthesis  Increased  is  GH  indicating  Although a  in vitro  n o r m a l and  synthesis  synthesis  protein  of  to  amino a c i d u p t a k e ,  (53).  ribosomes,  tRNA  into  i s t h u s d e p e n d a n t on  amino a c i d u p t a k e i s b l o c k e d  synthesis,  the  incorporated  r a t e o f amino a c i d u p t a k e f o r one  the  Protein  t o be  m i n u t e s . A f t e r the  returns  increased  number o f  i n t e r a c t s with  enzymes.  t o 30  of  through  the  i s added to c e l l s  c h a n g e f o r 20 an  amino a c i d s  e n t i r e process  several GH  subsequently  protein  content (41).  It  of is  unknown nuclei  whether  r e p r e s e n t s an i n c r e a s e  that are a c t i v e  an i n c r e a s e d The growth GH  this  number o f s a t e l l i t e  control  i n several  growth  respects. (55,56),  (56).  protein  synthesis  different  processes.  mechanisms  of  growth  (49,57,58),  growth  where GH e n h a n c e s t h e r a t e  synthesis  even  work  processes  these  rats,  cutting both  for  induced  uptake  requires  i s independant  and o c c u r s even i n  uptake  i s required from  that  for  the  f o r work hormonal  of t r a n s l a t i o n  there two  induced induced  of e x i s t i n g of  RNA RNA  can both cause  influences  of  which  by  on  o f work p e r f o r m e d  to which  growth,  another  (59),  hypophysectomized This allows  tenotomy  Muscle on  work  i n the  and can  synergistic  cut i s the gastrocnemius,  leads to a great i n c r e a s e  the  workload  of  M u s c l e work c a n be d e c r e a s e d  or  i t through f i x a t i o n -42-  close  by t h e m u s c l e ,  i t i s exposed.  most commonly  immobilizing  one  production.  by p e r f o r m i n g a s u r g i c a l  The m u s c l e  muscle  t h r o u g h a number o f e x p e r i m e n t s . Many  t h e s o l e u s and p l a n t a r i s .  abolished  f o r work  uptake  can o c c u r i n d e p e n d a n t l y of  o f b o t h t h e amount  increased  muscles.  co-factor  This indicates  e x p e r i m e n t s h a v e been p e r f o r m e d  the hormonal be  induced  i n the presence of i n h i b i t o r s  w h i c h h a v e no e n d o g e n o u s GH  control  (41),  differs  and h o r m o n e s  w h i c h h a s been d e m o n s t r a t e d of  f r o m work  (41,53).  Although these  growth  which  merely  amino a c i d  amino a c i d RNA  of  or  i s a required  (49,57,58).  The s y n t h e s i s o f new  stimulates  differs  i n work i n d u c e d g r o w t h ,  muscle  and  fibres,  but i s u n n e c e s s a r y  protein  number  nuclei (50).  W h i l e GH m e d i a t e d  the presence of i n h i b i t o r s are  muscle  growth  Insulin  the s y n t h e s i s of a t r a n s p o r t of  cell  o f GH m e d i a t e d  induced growth  muscle  i n synthesizing  i n the  of the  joint  on  which  i t acts,  which  is  o r by s e c t i o n i n g  effective  administered Different  in  in  promoting  controlled  combinations  i t s nerve  growth  were d e m o n s t r a t e d  of growth  contralateral  by c o m p a r i n g  animals.  Other normal,  would  of growth  limb  was  indicate  i s independant  which  time t h e i r  matched training  in  muscles  w i t h GH d a i l y  (60). Neither  regimen.  increase  group  was  A t t h e end o f t h e t e s t  compared its  i n muscle  fibre  increased  size,  p e r f o r m as w e l l had  two p o s s i b l e  possibility  was  the  to e x p l a i n new  -43-  o f GH  on  to t h e i r any  pair-  strength  t h e GH  treated  2 6 . 2 % g r e a t e r , and  d i a m e t e r o f 6-12% a s despite  tension,  and,  wei^.hl , t h e y d i d n o t  animals.  The r e s e a r c h e r s  these f i n d i n g s .  material  both  during  The q u a d r i c e p s , h o w e v e r ,  as t h o s e o f t h e c o n t r o l  that  induced  f o r 21 d a y s ,  period  p e r gram o f m u s c l e  hypotheses  work  of  Normal,  d i d n o t d e v e l o p any g r e a t e r  when e x p r e s s e d a s t e n s i o n  groups  (60,61,62).  given  cross-sectional  to untreated c o n t r o l s .  rats (59).  influences.  the e f f e c t s  r a t s w e r e 2 0 % h e a v i e r , had a q u a d r i c e p s w e i g h t an  of  f o o d i n t a k e was k e p t e q u i v a l e n t  controls  muscular  of t e n o t o m i z i n g  both  of hormonal  h y p e r t r o p h i e d , and a t r o p h i e d grown r a t s were t r e a t e d  growth.  to the non-tenotoraized  the degree  e x p e r i m e n t s have examined  fully  to  and s o l e u s o c c u r r e d , and t h e  t h e same  that  used  on  and h y p o p h y s e c t o m i z e d  of the tenotomized muscles  This  stimulation  the e f f e c t s  be  growth.  been  and work e f f e c t s  GH,  can  muscle  i n promoting muscle  of the p l a n t a r i s  control  Bovine  rats,  to stimulate  of hormonal  the gastrocnemius of both normal  ratio  in  of t h e s e t e c h n i q u e s have  independance  Compensatory growth  growth  doses  d e t e r m i n e how work and GH i n t e r a c t The  supply.  responsible  The  first  f o r the  increase  in  weight  Alternatively, to  a  was  the lack  not,  of tension  defect i n neuro-muscular  propogation of the c o n t r a c t i l e whether from  training  in  the rats  fact,  contractile  development  transmission impulse.  may h a v e been due  o r a change  i n the  I t i s unknown,  or having a longer  the time of c e s s a t i o n  protein.  however,  adaptation  o f GH t r e a t m e n t t o t e s t i n g  period  would  have  changed t h e r e s u l t s . In  another experiment  contractile determine  capacity the  effect  gastrocnemius  of  immobilization, contralateral weight the  and  work  rats  62%  muscle.  of the atrophied  muscles  control  in  the gastrocnemius  increased  by  58%  increase  i n the tension  made t o b o t h to  the  all in  of experiments  of the normal,  non-GH  (saline)  experimental relative  rats.  weight  of  the  increased  the  to those  was,  of  tensions  animals  compared  normal,  The  through  tetanic  compared (62).  to  were those  however,  no  non-atrophied  conditions to  contralateral treated  -44-  were  limb,  rats.  A  treated  of  and third  rats i n  and t h e o t h e r h y p e r t r o p h i e d . I n  t h e GH  t h e non  the e f f e c t s Comparisons  was made b e t w e e n t h e GH and t h e s a l i n e  one h i n d l i m b was a t r o p h i e d  size  i n the  to  muscles.  the muscles of  as  There  and h y p e r t r o p h i e d m u s c l e s  muscles  comparison which  developed  elaborate series  GH on a t r o p h i e d  and  65% r e s p e c t i v e l y  i n the non-treated c o n t r o l s .  An  the  o f t h e GH t r e a t e d  developed  control  in  atrophied  the  Twitch  activity,  studied  by 1 9 % when c o m p a r e d  animals.  and  were  muscle  was  of  EMG  GH a d m i n i s t r a t i o n  developed  contralateral  weight,  performance  control  weighed  control  untreated  muscle  o f GH on a t r o p h i e d  the  and  (61),  GH  treated treated  muscles controls.  increased With  GH  stimulation, muscles the  the  was  growth  which  t h a t GH  i n t u r n was Although  non-surgical  increased  protein  depending  on t h e s t i m u l u s .  increase  the  training  increases  the  collagen  synthesis  muscle  w e i g h t and to  hypertrophied  chronic  of  Isometric  muscle  (1,53).  fibre  the  by  strength  lead  to  performance  protein,  ability  performance  will  while  and GH  can  and  differ  tends  to  endurance  and m i t o c h o n d r i a l  size  (26%  vs.  proteins  also  in  the  stimulate  both the l a c k of  6-12%) i n GH  synthesis  of  A large increase  o f GH  and  weaker muscles  i n muscular  size  treated  collagen i n muscle  and  which  contractile  of normal muscles  -45-  i n normal  the  i s caused outwardly  (63,64). administration  improvements  muscles, i t remains d i f f i c u l t  to i n c r e a s e  in  rats  collagen  c h a r a c t e r i z e d by  t h e s e s t u d i e s i n d i c a t e t h a t GH  o f GH  GH  the d i s c r e p a n c y between the i n c r e a s e s i n  (60).  of a t r o p h i e d  work.  training  I t i s possible that  but f u n c t i o n a l l y  increases  synthesis  both  synthesized  of  authors  l e d t o a 50% i n c r e a s e  (49),  preferential  muscles  Although  the  proteins  the s a r c o p l a s m i c  hypersecretion  hypertrophied  The  r a t e of p r o t e i n  f o u n d i n t h e myopathy of a c r o m e g a l y , a d i s e a s e  by  the  actual  p e r f o r m a n c e and  due  hypertrophied  limb.  i s increased  Work i n d u c e d h y p e r t r o p h y has content  is  the b a s a l  amount o f m y o f i b r i l l a r  collagen  were  control  synthesis  work,  improved  and  d e t e r m i n e d by t h e amount o f m u s c u l a r  muscular  (50).  both a t r o p h i e d  always p r o p o r t i o n a l to the growth of the muscles  contralateral  concluded  of  the  to p r e d i c t  e l e m e n t s and humans.  in  may  improve  2-5 DISORDERS Abnormal l e v e l s or  absent  and  they  levels present  o f GH a r e f o u n d  a r e found with  i n two d i s e a s e  i n patients with  growth  states.  pituitary  failure,  relative  obesity,  retardation,  delayed  e a r l y m o t o r d e v e l o p m e n t and p r e m a t u r e a g i n g  changes  are  children  a r e commonly t r e a t e d w i t h  reversible  Pituitary age  after and  while  epiphyseal is  leads  GH  extent,  acromegaly closure  growth  t h i c k e n i n g of  occurring  bones  and  o f 5 0 % by t h e age o f 50 y e a r s  with a  and 8 9 % by 60 y e a r s ( 4 ) .  hypertension,  atherosclerotic  heart  diabetes  disease,  raellitus,  congestive  heart  c a r d i o m y o p a t h y , n e u r o p a t h y , and m y o p a t h y ( 4 ) .  The  myopathy  appear  functionally weakness,  of acromegaly  t o be o u t w a r d l y impaired,  easy  with  course  of acromegaly and  muscle hypertrophy  but  the v i c t i m s complaining and d e c r e a s e d  have r e p o r t e d  (68), while  uncommon f i n d i n g  in distribution  i s unusual i n that  hypertrophied,  fatiguability,  ( 6 3 , 6 4 , 6 6 , 6 7 ) . Some a u t h o r s  proximal  soft  and d e f o r m i t i e s o f t h e  intolerance,  variable  and  A c r o m e g a l y h a s an i n s i d i o u s o n s e t  include glucose  of  with the  GH e x c e s s i n  linear  Complications  the  o f GH,  f a c e , h a n d s , and f e e t . I t i s n o t a b e n i g n d i s e a s e ,  failure,  These  deficient  f r o m GH e x c e s s e s  eventually leading to coarsening  mortality  often  and  presentation.  results  (2).  (65).  injections.  to increased  c h a r a c t e r i z e d by g r a d u a l  tissues, skull,  certain  the c l i n i c a l  individuals  gigantism,  a  tumors can l e a d t o h y p e r s e c r e t i o n  of onset determining  prepubertal  to  Low  (66).  The  report  muscles  are  actually  of  muscular  exercise  strength  others  the  tolerance  gains that  myopathy  early i n this  is  ( 6 6 ) , w h i c h i s where t h e g r e a t e s t  occurs  (60). -46-  B i o p s i e s of a f f e c t e d  isa  usually degree muscles  have  revealed  variable  others hypertrophy been  changes,  o f Type I f i b r e s  shown t o be n o r m a l ,  single  b i o p s y from  reported  more  atrophy,  changes  (67),  particularly  demonstrated  acromegaly  to  than  feel  be  and  Type I I f i b r e s  have  while other of  more r e l a t e d  t h e serum l e v e l s  t h a t the somatomedin  to  o f GH levels  within  the  (63,64).  fibres,  (63,64).  a  s t u d i e s have  l i b fibres  occasional necrotic  increase i n connective tissue  appear  authors  (63,64).  (67)  a t r o p h i e d and h y p e r t r o p h i e d  one i n d i v i d u a l  B i o p s i e s have a l s o pronounced  some s h o w i n g n o r m a l  The  and a  myopathic  duration  of  (64,66),  although  correlate  closely  the some  to the  degree of involvement ( 4 6 ) . 3-GH 3-1  AND  ATHLETES  INTRODUCTION Athletes  performance. preparation in  the  will  In a d d i t i o n  g i v e the a t h l e t e  use.  Canada  share  doping  control  athletes.  users  physical  to recent advances i n a t h l e t e  training,  an a d d i t i o n a l  To the  have  increasing  i n t h e hope  that  h a s become  procedures date,  and a t t e m p t s  h a v e been made  been  f o r major  and  disciplined.  against steroid -47-  use from  use,  and  of  carded directed  and  There other  to  comprehensive  competitions  of a n a b o l i c s t e r o i d  detected  pressure  and h a v e i n s t i t u t e d  Council  t h e s e m e a s u r e s h a v e been p r i m a r i l y  eradication  they  increasingly  S p o r t C a n a d a and t h e S p o r t s M e d i c i n e  these concerns,  increase  c o m p e t i t i v e edge.  s p o r t community  about t h e use of d r u g s ,  their  towards  their  and a n a b o l i c a g e n t s  international  alarmed  to improve  and m o n i t o r i n g , t h e r e h a s been a d i s t r e s s i n g  use of drugs  The  curb  are c o n s t a n t l y s t r i v i n g  several is  also  regulatory  bodies. policy  The  University  of drug t e s t i n g  United  States,  regulations. athletes  As  have  agents, for  the  N.C.A.A.  has r e c e n t l y  has  the p r o b a b i l i t y abandoned  of  also  reportedly  is  found  invoked  s t e r o i d s i n favour  of  The  however,  widely  used  anti-doping  other  some  anabolic  drug of c h o i c e  prevalence  evidence  of  of  GH  i t was  s p e c i m e n s t e s t e d a t t h e W o r l d T r a c k and  C h a m p i o n s h i p s i n H e l s i n k i i n 1983 ( 7 5 ) ,  be  a  In the  increases,  t h a t GH i s t h e c u r r e n t  unknown,  i n urine  instituted  athletes.  detection  a t h l e t e s (69,70,71,72,73,74).  supplementation  to  Calgary  fora l l inter-collegiate  and i t i s r e p o r t e d  many  Field  of  in football  players  and i t i s  ( 6 9 ) , and  thought  bodybuilders  (71,73,76). 3-2 ADMINISTRATION There injection drugs  are  two  principal  o f e x o g e n o u s GH,  in  an a t t e m p t  modes  or the o r a l  of  GH  supplementation;  a d m i n i s t r a t i o n of various  to s t i m u l a t e the r e l e a s e of  endogenous  GH  from t h e p i t u i t a r y . Until recovered limited  recently  f r o m human c a d a v e r  supply.  deficient  the only  e x o g e n o u s GH  pituitaries,  While i t s intended  to  the  companies  producing  r e c o m b i n a n t DNA t e c h n o l o g y approved  for  u s e was i n t h e t r e a t m e n t  disease  (77,78,79).  biosynthetic  GH t h r o u g h  in bacteria.  The o n l y  formation -48-  o f GH  d i v e r t e d to a t h l e t e s  the  form  i n about 30% of t h e  due  Several use  of  currently  u s e h a s an e x t r a m e t h i o n i n e g r o u p a t t a c h e d  which has l e d t o a n t i b o d y  that  GH h a s now been d i s c o n t i n u e d  fear of C r e u t z f e l d t - J a k o b are  was  w h i c h was i n r e l a t i v e l y  c h i l d r e n , some s u p p l i e s were b e i n g  ( 7 0 ) . The u s e o f human p i t u i t a r y  available  to  i t ,  children  treated have,  (79). but  I t i s not  there  is  known what e f f e c t s t h e s e a n t i b o d i e s  speculation  e n d o g e n o u s GH  (77,79). This  methional-GH  has  its  use  (77).  duplicate  to  reports juice",  expect  some a u t h o r s  athletes  using  which i s represented  c a s e s i t was  a c t u a l l y found  Athletes clonidine  also  and  pituitary.  use  most  widespread  use  the  of  tryptophan selling vitamin of  book  pending 3-3  and  food  and  to  be  an  available  Branch  of  the  arginine,  stores.  new  and  of  has  In  response to  the  d r u g s and  the  possible  Federal suspended  vasopressin, from  has  public.  The  ornithine  and  promoted  best in  increased  use  effects,  the  Government their  the used  through a  been w i d e l y  their  i n some  their ingestion  lysine,  also  (70,77).  GH  general  In  "gorilla  commonly  been p o p u l a r i z e d  t h e i r use  as  steroid  and  and  are  although  release  amino a c i d s ,  has  to  propranolol,  the  GH  (79).  there  (70),  anabolic  against exact  near f u t u r e  p r i m a t e GH  concerns about  them as  further  recently  distribution  testing.  POTENTIAL USES There  lead  health  Protection  reclassified  releasers  (80),  amino a c i d s  Health  as  i n both a t h l e t e s  GH  athletes  GH,  with  biosynthetic  t e s t i n g an  biosynthetic  stimulate  the  interfere  a substance r e f e r r e d  s i n g l e amino a c i d s as  and  and  readily  s u b s t a n c e s , however, are become  currently  drugs i n c l u d i n g  L-Dopa t o  The  to a d v i s e  to market i t i n the  human p i t u i t a r y  of  t h e y may  p o t e n t i a l c o n s e q u e n c e of  Other companies are  and  addition  caused  that  will  to  however,  i s no  published  evidence that  improvements i n performance. mostly  in l i f t e r s  and -49-  GH  supplementation  There are  bodybuilders,  numerous  about the  will  claims, potential  beneficial  effects  lbs.)  lean  in  o f GH. T h e r e a r e r e p o r t s o f l a r g e g a i n s  body  weight  p r o p o n e n t c l a i m s "Wow, for  (70,71,73,76)  i s this  great  permanent muscle g a i n s  gain  after  stuff!  People  p e r day  genetics  as i t w i l l  occur,  This  said  use  (81).  Other users  that the e f f e c t s  A few s i d e  has not l e d t o s p e c t a c u l a r changes  anabolic  s t e r o i d s as i n j e c t a b l e  The  evidence  currently  GH  in  strength  and  power  l o w body f a t and  is  less  alone,  supported of  animals  outwardly clear  that  predicted that is  and n o t c o n t r a c t i l e  clear  muscle  I t s influence  certain.  The  elements.  This  in  apparent connective  possibility i s  by t h e l a c k o f p e r f o r m a n c e i m p r o v e m e n t s i n t h e m u s c l e s treated  with  hypertrophied  and  in  but f u n c t i o n a l l y  the p o t e n t i a l without  GH,  effects  f u r t h e r study,  t h e u s e o f GH s u p p l e m e n t a t i o n  unlikely  a  good  e n h a n c e m e n t o f m u s c l e b u l k may be due t o i n c r e a s e s i n tissue  of  Some o f i t s e f f e c t s a r e  a r e of prime importance. sports  and  Assessment  does not i n d i c a t e  useful  and b u l k  effects)  (70,77).  f r o m t h e u s e o f GH i n a t h l e t i c s .  definition  side  can  by t h e m i s r e p r e s e n t a t i o n o f  available  where  effects  ( 7 0 ) and t h a t i t s  (77,82).  benefit  body-building  10,000  a r e n o t so i m p r e s s e d ,  o f GH a r e o v e r r a t e d  GH's i n f l u e n c e i s f u r t h e r c o m p l i c a t e d  to  t h a t c a n remedy bad  however..... Even w i t h a l l t h a t , ( p o t e n t i a l  we LOVE t h e s t u f f . " have  grow.  drug  can e a t  One drug  who u s e i t c a n e x p e c t  i s the only  make a n y b o d y  use.  I t i s the best  30 t o 40 l b s o f m u s c l e i n t e n weeks i f t h e y  calories  GH  (30-40  to disappear.  -50-  the  acromegalics  weaker m u s c l e s .  o f GH on  athletes  however,  i t i s equally  with It is  cannot  i n athletes i s a practice  be  clear that  I n a d d i t i o n t o GH potential t h a t GH  u s e s f o r GH  can  delayed  efficacy  while  others  been  used  day  union  that  with  primary  and  results  (85).  to r e v e r s e  some  debilitating  GH  are  that  may  supplementation  reported  i n animals  and  report  b e n e f i t ( 8 4 ) . GH  (83),  has  also  osteoporosis  of  the  catabolic  and  aging.  in that  with  I t i s p o s s i b l e t h a t GH  numerous  become  becomes  effects bones  anecdotal s u c h as  of  the  well  a  arthritis,  to  complications  Jacob Disease, Acquired  insidious,  health  will  changes  associated irreversible  problem  Although  o c c u r r i n g i n GH  the  f e a t u r e s and  feet  there  users,  a shortened  antibodies  cause a r e l a t i v e  GH  o f GH  the  there  itself  are  injection  the  and  -51-  no are  i t s early  span.  which  the  There may  use  diabetes, i s also  neutralize  deficiency.  In a d d i t i o n to  possibility  of C r e u t z f e ^ l hepatitis  Syndrome ( A I D S ) i f n e e d l e s a r e not  are  Prolonged  p o t e n t i a l problems of  techniques  GH  there  including  life  if  t h i c k e n i n g of  (70,71,73,81).  complications  o f GH  Immuno-Deficiency  sterile  of  other  problem  and  major  h a n d s and  m y o p a t h i e s and  e n d o g e n o u s GH  i s an  problems  a c c o u n t s of a t h l e t e s s u f f e r i n g from  face,  potential  ethical  widespread.  coarsening  lead  and  Acromegaly  documented c a s e s of a c r o m e g a l y  and  some  inconclusive  secondary  diseases  serious medical  supplementation.  disease  the  no  be  POTENTIAL PROBLEMS  with  the  fractures is  may  been  ( 8 3 ) , h o w e v e r , some a u t h o r s  i s of  treat  used  There  may  fracture healing  i t s use  favourable  be  associated 3-4  feel  a t h l e t e s , there  a t h e r a p u t i c a g e n t . I t has  i n uncomplicated  to  potentially one  as  in healthy  speed e x p e r i m e n t a l  humans w i t h its  use  employed.  and  shared  The issues  medical  deter  i n sports  the  prospect  athlete  structure  desire  of parents  the  abuse  vast  a  to  demonstrated  that  i n the quest  ergogenic  aids  and  possibility avert  requiring  potential  forvictory.  aging,  however,  to  regulation  of f a i r  to enforce,  that  of  History play  are  GH GH has  often  drugs  and  use  may  and GH  i twill  about  the  and r e d u c e  only  p r o v e n way t o i m p r o v e p e r f o r m a n c e .  At p r e s e n t ,  o f GH w i l l  the  effects  is  value  -52-  studies  of  alter  i s the  surrounding  t a k e many s t u d i e s  especially i f further i n sport.  training  The m y s t i q u e  years to d i s p e l l ,  uses  become a f o r m i d a b l e  has t h e p o t e n t i a l to d r a m a t i c a l l y  o f modern a t h l e t i c s .  o f no p r a c t i c a l  make  magnitude.  speed h e a l i n g  and b e n e f i t s  the  athletics,  The c o n t r o l o f o t h e r  patterns  properties  strict  in sports  tragedies.  the  the  GH h a s l e d  undermining  r e m a i n s much t o be l e a r n e d  i talso  The  ( 7 0 , 7 1 , 8 0 ) . The o v e r w h e l m i n g  e t h i c s and t h e c o n c e p t  there  agent  giants  rewards of p r o f e s s i o n a l  a b u s e s o f GH. I t i s p o s s i b l e  theraputic  for i t s  a l l costs.  c h i l d r e n succeed  h a s been d i f f i c u l t  present  ethical  support  of pure b i o s y n t h e t i c  sport  become a p r o b l e m o f t r e m e n d o u s At  to win at  o f GH t r e a t e d  t o have t h e i r  financial  availability  lost  supply  of organized  distinct  of s c i e n t i f i c  who i s d e t e r m i n e d  predictions  present  t o t h e major  and t h e p o t e n t i a l h a z a r d s o f i t s use w i l l n o t  o f an u n l i m i t e d  chilling  and  i n comparison  s u r r o u n d i n g GH u s e . The l a c k  efficacy  to  problems pale  conclude  and many that i t  BIBLIOGRAPHY 1  GRODSKY, G.M. C h e m i s t r y and F u n c t i o n o f t h e Horraones:IV P i t u i t a r y and H y p o t h a l a m u s . I n : H a r p e r s R e v i e w of_ B i o c h e m i s t r y , ( 1 9 8 2 ) . M a r t i n , D., M a y e s , P . a n d R o d w e l l . V . ( E d i t o r s ) . 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