Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression.
Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression.
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缺氧通过抑制 NRF1 激活的 StAR 表达来减少小鼠睾丸间质细胞的睾酮合成
DOI：
10.18632/oncotarget.14842
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发表时间：
2017-03-07
期刊：
影响因子：
--
通讯作者：
Zhu L
中科院分区：
文献类型：
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作者：
Wang X;Pan L;Zou Z;Wang D;Lu Y;Dong Z;Zhu L
男性生育障碍在所有不孕症病例中占一半。缺氧引起的睾酮水平降低可能导致生殖系统和其他器官的疾病。低氧暴露导致NRF 1显著降低。软件分析表明，类固醇生成急性调节蛋白（星星）的启动子区含有NRF 1结合位点，表明NRF 1促进睾丸类固醇生成。本研究的目的是确定NRF 1参与睾酮的合成;缺氧条件下，睾酮合成的减少是由于NRF 1表达降低所致。我们设计了体内和体外实验。缺氧条件下，睾丸间质细胞NRF 1表达和睾酮水平均显著降低。过表达和干扰NRF 1可诱导星星升高和睾酮降低。ChIP结果证实了NRF 1与星星启动子区的结合。总之，NRF 1表达的下降下调了星星的水平，最终导致睾酮合成的减少。
Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis.