Bao A-M, Fischer D F, Wu Y-H, Hol E M, Balesar R, Unmehopa U A, Zhou J-N, Swaab D F
Netherlands Institute for Brain Research, Amsterdam, The Netherlands.
Mol Psychiatry. 2006 Jun;11(6):567-76. doi: 10.1038/sj.mp.4001800.
We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.
我们研究了雄激素对人类促肾上腺皮质激素释放激素（CRH）表达的直接作用的可能性，CRH在下丘脑-垂体-肾上腺（HPA）轴中起核心作用。在人类下丘脑室旁核（PVN）的神经元中发现了CRH与核/细胞质雄激素受体（AR）的共定位。随后，通过神经母细胞瘤细胞中的凝胶迁移实验和共转染分析了人类CRH启动子中的潜在雄激素反应元件（ARE）。在睾酮存在的情况下，重组人AR特异性结合到CRH-ARE。AR与睾酮共同表达通过ARE抑制CRH启动子活性。我们得出结论，雄激素可能通过AR与CRH-ARE结合直接影响人类PVN中的CRH神经元，这可能对情绪障碍的性别特异性发病机制产生影响。
