Kumar Sudeep, Kim Hyo Jeong, Lee Chul-Ho, Choi Hueng-Sik, Lee Keesook
School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
Reprod Sci. 2022 Mar;29(3):955-962. doi: 10.1007/s43032-021-00554-x. Epub 2021 Apr 23.
Testosterone, the male sex hormone, is necessary for the development and function of the male reproductive system. Biosynthesis of testosterone in mammals mainly occurs in testicular Leydig cells. Many proteins such as P450c17, 3β-HSD, and StAR are involved in testicular steroidogenesis. DAX1 is essential for sex development and interacts with nuclear receptors such as steroidogenic factor 1 to inhibit steroidogenesis. In this study, we investigated the role of DAX1 in testicular steroidogenesis in vivo by generating Leydig cell-specific DAX1-knockout mice. Radioimmunoassay revealed that the levels of testosterone and progesterone were higher in Leydig cell-specific DAX1-knockout testes than in the testes from wild-type mice during the first 3-4 weeks of aging. In addition, the expression levels of steroidogenic genes, such as StAR, P450c17, P450scc, and 3β-HSD, were considerably higher in the testes from DAX1-knockout mice. DAX1-deficient mouse testes seemed to attain early puberty with the acceleration of germ cell development. These data suggest that DAX1 regulates the expression of steroidogenic genes, and thereby controls and fine-tunes steroidogenesis during testis development.
睾酮，即雄性性激素，对于雄性生殖系统的发育和功能至关重要。哺乳动物体内睾酮的生物合成主要发生在睾丸间质细胞中。许多蛋白质，如细胞色素P450c17、3β -羟基类固醇脱氢酶（3β-HSD）和类固醇生成急性调节蛋白（StAR），都参与睾丸类固醇生成过程。剂量敏感型性别反转肾上腺发育不全综合征蛋白1（DAX1）对于性别发育至关重要，并与类固醇生成因子1等核受体相互作用以抑制类固醇生成。在本研究中，我们通过构建睾丸间质细胞特异性DAX1基因敲除小鼠，研究了DAX1在体内睾丸类固醇生成中的作用。放射免疫分析显示，在衰老的前3至4周内，睾丸间质细胞特异性DAX1基因敲除小鼠睾丸中的睾酮和孕酮水平高于野生型小鼠睾丸中的水平。此外，DAX1基因敲除小鼠睾丸中类固醇生成基因，如StAR、P450c17、细胞色素P450侧链裂解酶（P450scc）和3β-HSD的表达水平显著更高。DAX1缺陷型小鼠睾丸似乎随着生殖细胞发育的加速而提前进入青春期。这些数据表明，DAX1调节类固醇生成基因的表达，从而在睾丸发育过程中控制并微调类固醇生成。
