title: Fetal ethanol exposure alters pituitary-adrenal sensitivity to dexamethasone suppression.
abstract: The present study investigated the hypothesis that a deficit in feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the hormonal hyperresponsiveness seen in fetal ethanol-exposed rats. Male and female Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF) and ad lib-fed control (C) treatment groups were tested in adulthood. The effects of dexamethasone (DEX) blockade on basal and stress corticosterone (CORT) levels and stress adrenocorticotropin (ACTH) levels were examined over a 36-h period. Stress CORT and ACTH levels after DEX administration at the trough (AM) and peak (PM) of the CORT circadian rhythm were compared. DEX administration significantly suppressed both resting and stress levels of CORT and ACTH in all animals, regardless of prenatal treatment. Importantly, E animals did not differ 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 from PF and C males, whereas E females had increased stress levels of CORT compared to PF and C females. In contrast, at the peak of the circadian rhythm, E males showed increased stress levels of CORT but not ACTH, whereas E females showed increased stress levels of both CORT and ACTH compared to males and females in respective control groups. These data support the hypothesis that E animals may exhibit deficits in HPA feedback inhibition compared to controls and suggest a sex-specific difference in sensitivity of the mechanism underlying HPA hyperresponsiveness.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Osborn
authors.forename: C K
authors.initials: CK
authors.lastname: Kim
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: L
authors.initials: L
authors.lastname: Herbert
authors.forename: J
authors.initials: J
authors.lastname: Weinberg
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001143:Arousal / Q000502:physiology; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
chemical_list: D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone