Contribution of Leydig and Sertoli Cells to Testosterone Production in Mouse Fetal Testes
Contribution of Leydig and Sertoli Cells to Testosterone Production in Mouse Fetal Testes
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DOI：
10.1210/me.2012-1256
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Morohashi, Ken-ichirou
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文献类型：
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作者：
Shima, Yuichi;Miyabayashi, Kanako;Morohashi, Ken-ichirou
睾酮是雄激素生物合成的最终产物，而间质细胞是雄激素的主要来源。在哺乳动物睾丸中，两种不同的间质细胞，胎儿间质细胞和成年间质细胞，依次发育，这两种细胞类型在形态和功能上都不同。众所周知，成年间质细胞通过分泌睾酮来维持男性生殖功能。然而，胎儿间质细胞是否能产生睾酮一直存在争议，胎儿睾丸中睾酮的合成途径也不完全清楚。在本研究中，我们培育了在胎儿间质细胞特异性Ad4BP/SF-1 （Nr5a1）基因增强子的控制下表达增强绿色荧光蛋白的转基因小鼠。通过突变启动子中的LIM同源结构域转录因子（LHX9）结合序列制备转基因构建物，使未分化睾丸细胞中的启动子活性消失。这些转基因小鼠被用来收集高纯度的胚胎间质细胞。分析了胎儿间质细胞、胎儿支持细胞和成体间质细胞的基因表达和甾体生成酶活性。结果表明，由于缺乏Hsd17b3的表达，胎儿间质细胞只能合成雄烯二酮，胎儿Sertoli细胞将雄烯二酮转化为睾酮，而成年间质细胞则自行合成睾酮。目前的研究表明，在小鼠胎儿睾丸中，睾丸间质细胞和支持细胞都是合成睾酮所必需的。（分子内分泌学27:63-73,2013）
Testosterone is a final product of androgenic hormone biosynthesis, and Leydig cells are known to be the primary source of androgens. In the mammalian testis, two distinct populations of Leydig cells, the fetal and the adult Leydig cells, develop sequentially, and these two cell types differ both morphologically and functionally. It is well known that the adult Leydig cells maintain male reproductive function by producing testosterone. However, it has been controversial whether fetal Leydig cells can produce testosterone, and the synthetic pathway of testosterone in the fetal testis is not fully understood. In the present study, we generated transgenic mice in which enhanced green fluorescence protein was expressed under the control of a fetal Leydig cell-specific enhancer of the Ad4BP/SF-1 (Nr5a1) gene. The transgene construct was prepared by mutating the LIM homeodomain transcription factor (LHX9)-binding sequence in the promoter, which abolished promoter activity in the undifferentiated testicular cells. These transgenic mice were used to collect highly pure fetal Leydig cells. Gene expression and steroidogenic enzyme activities in the fetal Leydig cells as well as in the fetal Sertoli cells and adult Leydig cells were analyzed. Our results revealed that the fetal Leydig cells synthesize only androstenedione because they lack expression of Hsd17b3, and fetal Sertoli cells convert androstenedione to testosterone, whereas adult Leydig cells synthesize testosterone by themselves. The current study demonstrated that both Leydig and Sertoli cells are required for testosterone synthesis in the mouse fetal testis. (Molecular Endocrinology 27: 63-73, 2013)