FETAL ETHANOL EXPOSURE ALTERS PITUITARY-ADRENAL SENSITIVITY TO DEXAMETHASONE SUPPRESSION

The present study investigated the hypothesis that a deficit in feedba ck inhibition of the hypothalamic-pituitary-adrenal (HPA) axis may und erlie the hormonal hyperresponsiveness seen in fetal ethanol-exposed r ats. Male and female Sprague-Dawley rats from prenatal ethanol (E), pa ir-fed (PF) and ad lib-fed control (C) treatment groups were tested in adulthood. The effects of dexamethasone (DEX) blockade on basal and s tress corticosterone (CORT) levels and stress adrenocorticotropin (ACT H) levels were examined over a 36-h period. Stress CORT and ACTH level s after DEX administration at the trough (AM) and peak (PM) of the COR T circadian rhythm were compared. DEX administration significantly sup pressed both resting and stress levels of CORT and ACTH in all animals , regardless of prenatal treatment. Importantly, E animals did not dif fer from PF and C animals in basal CORT. However, E males and females had significantly higher stress levels of CORT and/or ACTH than PF and C animals, and further, showed differential responsiveness following DEX administration depending on the time of day when testing occurred. At the trough of the CORT circadian rhythm, E males did not differ fr om PF and C males, whereas E females had increased stress levels of CO RT compared to PF and C females. In contrast, at the peak of the circa dian rhythm, E males showed increased stress levels of CORT but not AC T?I, whereas E females showed increased stress levels of both CORT and ACTH compared to males and females in respective control groups. Thes e data supper the hypothesis that E animals may exhibit deficits in HP A feedback inhibition compared to controls and suggest a sex-specific difference in sensitivity of the mechanism underlying HPA hyperrespons iveness. Copyright (C) 1996 Elsevier Science Ltd.