title: Prenatal ethanol exposure alters the effects of gonadectomy on hypothalamic-pituitary-adrenal activity in male rats.
abstract: Prenatal ethanol exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. In adulthood, ethanol-treated rats show altered gonadal hormone responses and reproductive function, and increased HPA responsiveness to stressors. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that the gonadal hormones play a role in mediating prenatal ethanol effects on HPA function. To examine a possible testicular influence on HPA activity in males, we compared the effects of gonadectomy on HPA stress responses of adult male offspring from ethanol, pair-fed (PF) and ad libitum-fed control dams. Intact ethanol-treated rats showed increased adrenocorticotrophic hormone (ACTH) but blunted testosterone and luteinising hormone (LH) responses to restraint stress, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels compared to those observed in PF and/or control rats. Gonadectomy: (i) significantly increased ACTH responses to stress in control but not ethanol-treated and PF males; (ii) eliminated differences among groups in plasma ACTH and AVP mRNA levels; and (iii) altered LH and gonadotrophin-releasing hormone responses in ethanol-treated males. Taken together, these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure, with normal testicular influences on HPA function markedly reduced in ethanol-treated animals. A decreased sensitivity to inhibitory effects of androgens could contribute to the HPA hyperresponsiveness typically observed in ethanol-treated males.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Lan
authors.forename: F
authors.initials: F
authors.lastname: Yamashita
authors.forename: A G
authors.initials: AG
authors.lastname: Halpert
authors.forename: L
authors.initials: L
authors.lastname: Ellis
authors.forename: W K
authors.initials: WK
authors.lastname: Yu
authors.forename: V
authors.initials: V
authors.lastname: Viau
authors.forename: J
authors.initials: J
authors.lastname: Weinberg
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D002369:Castration; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013315:Stress, Psychological / Q000503:physiopathology; D013737:Testis / Q000502:physiology*; D013739:Testosterone / Q000097:blood
chemical_list: D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D007987:Gonadotropin-Releasing Hormone; D000431:Ethanol; D013739:Testosterone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone