Rubinow David R, Roca Catherine A, Schmidt Peter J, Danaceau Merry A, Putnam Karen, Cizza Giovanni, Chrousos George, Nieman Lynnette
Behavioral Endocrinology Branch, National Institute of Mental Health, Building 10-CRC, 10 Center Drive MSC 1276, Bethesda, MD 20892-1276, USA.
Neuropsychopharmacology. 2005 Oct;30(10):1906-12. doi: 10.1038/sj.npp.1300742.
Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (p<0.05, 0.005, and 0.01, respectively) during testosterone replacement compared with the induced hypogonadal condition (leuprolide plus placebo); cortisol area under the curve was lower at a trend level (p<0.1). Paradoxically, CRH-stimulated corticotropin (ACTH) was increased significantly during testosterone replacement (p<0.05). The cortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (p<0.1). A mixed effects regression model showed that testosterone but not estradiol or CBG significantly contributed to the variance of cortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.
尽管观察到下丘脑-垂体-肾上腺（HPA）轴活动存在年龄依赖性的性别差异，但雄激素在男性HPA轴活动调节中的作用尚未得到研究。我们通过对10名男性（年龄18 - 45岁）在使用醋酸亮丙瑞林进行性腺抑制期间以及在亮丙瑞林基础上加用睾酮期间进行促肾上腺皮质激素释放激素（CRH）刺激试验，来评估这一作用。与诱导性腺功能减退状态（亮丙瑞林加安慰剂）相比，在补充睾酮期间，CRH刺激后的皮质醇水平以及皮质醇峰值和最大皮质醇波动均显著降低（分别为p<0.05、0.005和0.01）；皮质醇曲线下面积在趋势水平上较低（p<0.1）。矛盾的是，在补充睾酮期间，CRH刺激后的促肾上腺皮质激素（ACTH）显著增加（p<0.05）。作为肾上腺敏感性指标的皮质醇:ACTH比值在补充睾酮期间较低（p<0.1）。混合效应回归模型显示，睾酮而非雌二醇或皮质类固醇结合球蛋白（CBG）对皮质醇的变异有显著贡献。这些数据表明，睾酮调节男性CRH刺激的HPA轴活动，对ACTH和皮质醇的不同影响提示对皮质醇的抑制作用存在外周（肾上腺）位点。我们的结果进一步表明，先前描述的年轻男性与年轻女性相比增强的刺激HPA轴活动不能归因于睾酮对该轴的激活上调。
