Lan N, Yamashita F, Halpert A G, Ellis L, Yu W K, Viau V, Weinberg J
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
J Neuroendocrinol. 2006 Sep;18(9):672-84. doi: 10.1111/j.1365-2826.2006.01462.x.
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.
产前乙醇暴露对下丘脑 - 垂体 - 肾上腺（HPA）轴和性腺（HPG）轴的发育有显著影响。成年后，经乙醇处理的大鼠表现出性腺激素反应和生殖功能改变，以及HPA对应激源的反应性增加。重要的是，产前乙醇对成年雄性和雌性的应激反应有不同影响，这增加了性腺激素在介导产前乙醇对HPA功能影响中起作用的可能性。为了研究睾丸对雄性HPA活性的可能影响，我们比较了去势对来自乙醇处理组、配对喂养（PF）组和自由摄食对照组母鼠的成年雄性后代HPA应激反应的影响。完整的经乙醇处理的大鼠显示促肾上腺皮质激素（ACTH）增加，但对束缚应激的睾酮和促黄体生成素（LH）反应减弱，与PF组和/或对照组大鼠相比，应激诱导的精氨酸加压素（AVP）mRNA水平没有升高。去势：（i）显著增加了对照组雄性对压力的ACTH反应，但对经乙醇处理和PF组雄性没有影响；（ii）消除了各组血浆ACTH和AVP mRNA水平的差异；（iii）改变了经乙醇处理雄性的LH和促性腺激素释放激素反应。综上所述，这些发现表明，产前乙醇暴露会改变HPA和HPG轴的中枢调节，在经乙醇处理的动物中，睾丸对HPA功能的正常影响明显降低。对雄激素抑制作用的敏感性降低可能导致经乙醇处理的雄性中通常观察到的HPA反应性增强。
