Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal regulation after adrenalectomy and corticosterone replacement.

BACKGROUND: Previous studies have demonstrated that rats prenatally exposed to ethanol (E) exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness, demonstrated by increased and/or prolonged elevations of adrenocorticotropin (ACTH) and/or corticosterone (CORT) after stress. This study investigated possible mechanisms of HPA hyperresponsiveness in E rats by manipulating CORT feedback regulation of HPA activity via adrenalectomy (ADX) with or without CORT replacement.

METHODS: Male Sprague-Dawley rat offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) groups were tested at 90 to 120 days of age. Rats were either sham-operated or underwent ADX, with or without CORT replacement. CORT (25 microg/ml) was replaced via the drinking water to achieve basal plasma CORT levels and maintain a phasic CORT signal. Seven days after surgery, animals were decapitated at the diurnal peak either under basal conditions or after a 15-min restraint stress, and trunk blood was collected.

RESULTS: After ADX, loss of the CORT feedback signal resulted in increased plasma ACTH in all groups compared with those in sham animals. In addition, under basal conditions, ADX E rats had significantly greater plasma ACTH levels than both PF and C rats. However, no differences were seen in ADX rats after stress. CORT replacement after ADX was partially effective in normalizing ACTH levels under both basal and stress conditions, with no differences among E, PF, and C animals.

CONCLUSIONS: These results suggest that E males may exhibit enhanced stimulatory inputs to the hypothalamus, increased pituitary sensitivity to secretagogues, or both, which may be revealed after ADX. In contrast, E animals seem similar to controls in their ability to use an exogenous CORT signal to regulate HPA activity.