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Prenatal ethanol exposure : gonadal axis influences on hypothalamic-pituitary-adrenal responsiveness in prepubertal rats Halpert, Alison

Abstract

The mechanisms underlying altered hypothalamic-pituitary-adrenal (HPA) activity following prenatal ethanol exposure are unknown. Previous findings from our laboratory have revealed that rats prenatally exposed to ethanol (E) differ from their control counterparts in HPA responding both neonatally and in adulthood. Furthermore prenatal ethanol differentially alters HPA activity in males and females, suggesting a possible role for altered HPG function in HPA axis dysregulation. Prenatal ethanol exposure alters both activational and organizational effects of HPG hormones. This thesis was designed to determine if maturation of the HPA stress response is delayed in prepubertal E rats and to investigate the possibility that ethanol-induced changes to HPG organizational effects, as perhaps indicated by altered basal and/or stress hormone regulation, may underlie some of the differential HPA responsivity observed between E males and females compared to their control counterparts. Prepubertal (PN 25-26) male and female rats from ethanol, pair-fed (PF), and ad libitum-fed control (C) dams were examined at 0, 30 or 60 min following the onset of a 30 min restraint stress. Overall, prepubertal E pups were hyporesponsive to stressors compared to controls, demonstrated by blunted CORT responses following restraint. Both MR and GR mRNA levels were differentially altered by stress in E compared to C pups, suggesting prenatal ethanol delayed and/or altered the development of CORT feedback mechanisms. HPG axis development was delayed and/or altered in E rats, as LH and E2 levels were lower and the LH/E2 correlation was absent in E compared to C female pups, and the HPG hormones responsivity to stressors was altered in both E males and females compared to controls. Importantly, prenatal ethanol both differentially altered the pattern of CORT responding, and interfered with the normal HPA/HPG hormone interactions in prepubertal males and females compared to control counterparts. These data indicate that prenatal ethanol delayed and/or altered HPA and HPG development during the prepubertal period. Furthermore HPA responding to stressors was differentially altered in prepubertal E males and females compared to their control counterparts, suggesting that altered HPA activity may be mediated, in part, by changes to the HPG organizational effects.

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