Gender difference in hypothalamic-pituitary-adrenal axis response to alcohol in the rat: activational role of gonadal steroids
Gender difference in hypothalamic-pituitary-adrenal axis response to alcohol in the rat: activational role of gonadal steroids
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DOI：
10.1016/s0006-8993(97)00525-8
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发表时间：
1997-08-22
期刊：
影响因子：
2.9
通讯作者：
Rivier, C
中科院分区：
文献类型：
--
作者：
Ogilvie, KM;Rivier, C
酒精管理激活下丘脑-垂体-肾上腺（HPA）轴的雄性和雌性大鼠，与女性分泌更多的促肾上腺皮质激素（ACTH）和皮质酮比男性在响应相同剂量的酒精。我们早期的工作表明，这种性别差异是由于性腺类固醇的激活作用。特别是，我们假设雄激素和雌激素都起作用，雄激素发挥抑制作用，而雌激素提高HPA的活性。在目前的研究中，我们通过手术去势和长期植入睾酮（T）、双氢睾酮（DHT）或雌二醇（E-2）来操纵雄性大鼠的类固醇环境来验证这一假设。包括完整的雄性和雌性大鼠作为对照。注射酒精（3 g/kg b.wt.，注射用）导致所有组的血液酒精水平、ACTH和皮质酮升高。然而，分泌的ACTH的量是更大的女性和去势男性植入E-2比在完整的男性。在去势的男性，无论雄激素植入，促肾上腺皮质激素的反应是中间的，与女性和男性之间的平均水平，但没有显着差异。与ACTH结果相反，在未接受类固醇植入的雌性和去势雄性中测得显著较高的皮质酮分泌。由于血液酒精水平（巴尔斯）组间无显著差异，这些结果不是由于酒精代谢的类固醇依赖性改变。由于ACTH数据证实了E-2的激活作用，我们试图确定这种类固醇是否调节下丘脑室旁核（PVN）中促肾上腺皮质激素释放因子（CRF）和精氨酸加压素（AVP）mRNA的水平。研究了4个预处理组：完整雄性、完整雌性、去势雄性和植入E-2的去势雄性。手术后两周，在收集脑前3小时给予酒精或溶媒。在完整的男性，酒精治疗的水平升高CRF和AVP mRNA的PVN，如前所述。相比之下，这种治疗降低了植入E-2的去势雄性动物的CRF mRNA。此外，类固醇预处理单独升高去势雄性CRF mRNA水平。虽然我们没有观察到CRF或AVP mRNA的E-2依赖性增加，但我们的数据确实支持性腺类固醇对PVN中这些mRNA表达的复杂影响。(C)1997年爱思唯尔科学有限公司
Alcohol administration activates the hypothalamic-pituitary-adrenal (HPA) axis of both male and female rats, with females secreting more adrenocorticotropin (ACTH) and corticosterone than males in response to the same dose of alcohol. Our earlier work suggested that this gender difference arises due to the activational effects of gonadal steroids. In particular, we hypothesized that both androgens and estrogens play a role, with androgens exerting an inhibitory influence while estrogens elevate activity of the HPA. In the present studies, we tested this hypothesis by manipulating steroidal milieu in male rats using surgical castration and chronic implantation of testosterone (T), dihydrotestosterone (DHT), or estradiol (E-2). Intact male and female rats were included as controls. Injection of alcohol (3 g/kg b.wt., i.p.) resulted in elevation of blood alcohol levels, ACTH and corticosterone in all groups. However, the amount of ACTH secreted was greater in females and castrated males implanted with E-2 than in intact males. In castrated males, regardless of androgen implantation, the ACTH response was intermediate, with mean levels between those of females and males, but not differing significantly from either. In contrast to the ACTH results, significantly higher corticosterone secretion was measured in females and castrated males which did not receive a steroid implant. Since there were no significant differences between groups in blood alcohol levels (BALs), these results are not due to steroid-dependent alterations in alcohol metabolism. Because the ACTH data confirmed an activational effect of E-2 we sought to determine whether this steroid regulated levels of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) mRNAs in the paraventricular nucleus of the hypothalamus (PVN). Four pretreatment groups were studied: intact males, intact females, castrated males, and castrated males implanted with E-2. Two weeks after surgery, alcohol or vehicle was administered 3 h before brains were collected. In intact males, alcohol treatment elevated levels of both CRF and AVP mRNAs in the PVN, as previously reported. In contrast, this treatment decreased CRF mRNA in castrated males implanted with E-2. In addition, steroid pretreatment alone elevated CRF mRNA levels in castrated males. Although we did not observe E-2-dependent increases in CRF or AVP mRNAs, our data do support a complex effect of gonadal steroids on expression of these mRNAs in the PVN. (C) 1997 Elsevier Science B.V.