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Alcohol Clin Exp Res. 2000 Jul;24(7):1110-9.

Effects of fetal ethanol exposure on pituitary-adrenal sensitivity to secretagogues.

Author information

1
Department of Anatomy, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

Abstract

BACKGROUND:

Rodents prenatally exposed to ethanol demonstrate hormonal hyper-responsiveness to stressors in adulthood. The present study examined the hypothesis that an increased sensitivity of the adrenal to ACTH and/or the pituitary to corticotropin releasing hormone (CRH) after dexamethasone suppression, may play a role in the hormonal hyper-responsiveness seen in fetal ethanol-exposed rats.

METHODS:

Sprague-Dawley males and females from prenatal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were tested in adulthood (90-120 days). Testing was done in a series of two experiments carried out during the trough of the corticosterone rhythm, the time of greatest sensitivity to feedback inhibition. Twenty-four to 48 hr before testing, jugular cannulae were implanted for hormone infusion and blood sample collection. In both experiments, animals were injected intraperitoneally with dexamethasone-21-phosphate (DEX) (15 microg/100 g body weight for males or 30 microg/100 g body weight for females) 3 hr before testing to suppress endogenous hypothalamic-pituitary-adrenal (HPA) activity. Animals were given a bolus infusion of ACTH (0-0.10 mg/rat) and blood samples (0.2 cc) were drawn at 60-min intervals over 240 min for determination of plasma corticosterone (CORT) levels (Experiment 1), or were given a bolus infusion of CRH (0-20 microg/kg body wt) and samples drawn at 0, 5, 15, and 30 min for determination of plasma ACTH and CORT levels (Experiment 2).

RESULTS:

As expected, sex differences in adrenal response to ACTH and pituitary response to CRH were observed; females had higher CORT and ACTH levels than males at all concentrations of ACTH and CRH. In addition, dose-response relationships between exogenously administered ACTH or CRH and plasma CORT were demonstrated; increasing concentrations of secretagogues resulted in higher and/or more prolonged CORT responses in both males and females. There were no significant differences among E, PF, and C males or females in adrenal sensitivity to ACTH. However, prenatal ethanol exposure altered pituitary sensitivity to CRH in both males and females. E and PF males demonstrated increased plasma ACTH but not CORT compared with C males, whereas E females demonstrated increased plasma ACTH and CORT levels compared with PF and C females after CRH infusion.

CONCLUSIONS:

Together these data suggest that (1) E animals do not show increased adrenal sensitivity to ACTH compared with controls; (2) the insult of prenatal ethanol exposure may result in altered pituitary sensitivity to CRH after DEX suppression; and (3) there may be a sex-specific difference in sensitivity of the mechanism(s) underlying HPA hyper-responsiveness.

PMID:
10924017
[Indexed for MEDLINE]

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