Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
Mol Cell Endocrinol. 2021 Jun 15;530:111286. doi: 10.1016/j.mce.2021.111286. Epub 2021 Apr 17.
Within pituitary gonadotropes, the gonadotropin-releasing hormone receptor (GnRHR) receives hypothalamic input from GnRH neurons that is critical for reproduction. Previous studies have suggested that androgens may regulate GnRHR, although the mechanisms remain unknown. In this study, we demonstrated that androgens positively regulate Gnrhr mRNA in mice. We then investigated the effects of androgens and androgen receptor (AR) on Gnrhr promoter activity in immortalized mouse LβT2 cells, which represent mature gonadotropes. We found that AR positively regulates the Gnrhr proximal promoter, and that this effect requires a hormone response element (HRE) half site at -159/-153 relative to the transcription start site. We also identified nonconsensus, full-length HREs at -499/-484 and -159/-144, which are both positively regulated by androgens on a heterologous promoter. Furthermore, AR associates with the Gnrhr promoter in ChIP. Altogether, we report that GnRHR is positively regulated by androgens through recruitment of AR to the Gnrhr proximal promoter.
在垂体促性腺激素细胞中，促性腺激素释放激素受体（GnRHR）接收来自 GnRH 神经元的下丘脑输入，这对于生殖至关重要。先前的研究表明，雄激素可能调节 GnRHR，但机制尚不清楚。在这项研究中，我们证明雄激素可在小鼠中正向调节 Gnrhr mRNA。然后，我们研究了雄激素和雄激素受体（AR）对代表成熟促性腺激素的永生化小鼠 LβT2 细胞中 GnRhr 启动子活性的影响。我们发现 AR 正向调节 Gnrhr 近端启动子，并且该效应需要相对于转录起始位点位于-159/-153 的激素反应元件（HRE）半位点。我们还鉴定了非共识的全长 HRE 位于-499/-484 和-159/-144，它们都可被雄激素在异源启动子上正向调节。此外，AR 通过募集到 GnRhr 近端启动子与 Gnrhr 启动子结合。总之，我们报告 GnRHR 可通过 AR 募集到 GnRhr 近端启动子而被雄激素正向调节。
