Central 5-alpha reduction of testosterone is required for testosterone's inhibition of the hypothalamo-pituitary-adrenal axis response to restraint stress in adult male rats.
Central 5-alpha reduction of testosterone is required for testosterone's inhibition of the hypothalamo-pituitary-adrenal axis response to restraint stress in adult male rats.
复制标题
DOI：
10.1016/j.brainres.2013.07.021
复制
发表时间：
2013-09-05
期刊：
影响因子：
2.9
通讯作者：
Brown R
中科院分区：
文献类型：
--
作者：
Handa RJ;Kudwa AE;Donner NC;McGivern RF;Brown R
在啮齿类动物中，下丘脑-垂体-肾上腺（HPA）轴由一种精确的调节机制控制，该机制受循环性腺和肾上腺激素的影响。在男性中，性腺切除术增加了促肾上腺皮质激素（ACTH）和皮质酮（CORT）对应激源的反应，雄激素替代使反应恢复到完整男性的水平。睾酮（T）调节HPA活性的作用可能是通过芳构化为雌二醇，或通过5α-还原为更有效的雄激素双氢睾酮（DHT）。为了确定后一种途径是否参与，我们评估了激素治疗后，或用5α-还原酶抑制剂finalide外周或中枢治疗后HPA轴对束缚应激反应的功能。最初，我们检查了性腺切除术改变CORT对束缚应激反应的时间过程。在性腺切除后48小时内，CORT反应明显增强。相应地，用5α-还原酶抑制剂非那肽处理完整雄性大鼠48小时，增强了CORT和ACTH对束缚应激的反应。外周注射雄鼠性腺切除与DHT或T 48小时减少ACTH和CORT反应约束应激。在施加应激之前，通过第三脑室给药非那肽可以阻断T的作用，但不能阻断DHT的作用。这些数据表明，T在调节HPA轴活性中的作用涉及中枢神经系统内的5α-还原酶。这些结果进一步加深了我们对T如何调节神经内分泌应激反应的理解，并表明5α还原为DHT是T作用的必要步骤。
In rodents, the hypothalamo-pituitary-adrenal (HPA) axis is controlled by a precise regulatory mechanism that is influenced by circulating gonadal and adrenal hormones. In males, gonadectomy increases the adrenocorticotropic hormone (ACTH) and corticosterone (CORT) response to stressors, and androgen replacement returns the response to that of the intact male. Testosterone (T) actions in regulating HPA activity may be through aromatization to estradiol, or by 5α-reduction to the more potent androgen, dihydrotestosterone (DHT). To determine if the latter pathway is involved, we assessed the function of the HPA axis response to restraint stress following hormone treatments, or after peripheral or central treatment with the 5α-reductase inhibitor, finasteride. Initially, we examined the timecourse whereby gonadectomy alters the CORT response to restraint stress. Enhanced CORT responses were evident within 48hrs following gonadectomy. Correspondingly, treatment of intact male rats with the 5α-reductase inhibitor, finasteride, for 48 hrs, enhanced the CORT and ACTH response to restraint stress. Peripheral injections of gonadectomized male rats with DHT or T for 48 hrs reduced the ACTH and CORT response to restraint stress. The effects of T, but not DHT, could be blocked by the third ventricle administration of finasteride prior to stress application. These data indicate that the actions of T in modulating HPA axis activity involve 5α-reductase within the central nervous system. These results further our understanding of how T acts to modulate the neuroendocrine stress responses and indicate that 5α reduction to DHT is a necessary step for T action.
登录
查看更多内容
影响因子：
--
作者：
CRITCHLOW, V;BARSELA, M;LIPSCOMB, HS
通讯作者：
LIPSCOMB, HS
影响因子：
7.6
作者：
Rubinow, DR;Roca, CA;Nieman, L
通讯作者：
Nieman, L
影响因子：
3.5
作者：
PELLETIER, G;VAN, LT;LABRIE, F
通讯作者：
LABRIE, F
影响因子：
5.3
作者：
Lund, TD;Hinds, LR;Handa, RJ
通讯作者：
Handa, RJ
影响因子：
4.1
作者：
BINGAMAN, EW;MAGNUSON, DJ;HANDA, RJ
通讯作者：
HANDA, RJ