Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor α
Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor α
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DOI：
10.1210/en.2004-1540
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发表时间：
2005-05-01
期刊：
影响因子：
4.8
通讯作者：
Habert, R
中科院分区：
文献类型：
--
作者：
Delbès, G;Levacher, C;Habert, R
现在公认的是，雌激素在男性生育能力中发挥作用，在胎儿/新生儿期间暴露于外源性雌激素可导致男性生殖障碍。然而，在胎儿和新生儿发育过程中，雌激素受体(ER)介导的调节男性生殖的过程仍然很不清楚。我们之前曾报道ERβ缺乏会影响小鼠的配子发生，但不会改变胎儿间质细胞的数量和分化功能。我们在这里显示，ERα缺陷小鼠(ERα(-/-))从胚胎d 13.5起表现出比野生型小鼠更高水平的睾丸睾酮分泌。这是由于每个胎儿间质细胞的类固醇合成活性较高，表现为这些细胞肥大，以及类似数量的间质细胞在睾丸中STAR、P450c17和P450scc的mRNA水平较高。由于在胎龄13.5天未产生黄体生成素，且在2日龄ERα缺陷小鼠的血浆中没有观察到黄体生成素浓度的变化，因此，黄体生成素可能不参与雌激素对胎儿和早期新生间质细胞的睾丸类固醇合成的影响。此外，ERβ失活并不改变ERα失活对类固醇合成的影响。最后，在器官培养系统中，1 mU己烯雌酚减少了野生型胎儿和新生儿睾丸的睾酮分泌，但不减少ERα(-/-)睾丸的睾酮分泌。因此，本研究表明，内源性雌激素通过直接作用于胎儿和新生儿发育早期的睾丸，在生理上通过ERα抑制类固醇的生成。
It is now accepted that estrogens play a role in male fertility and that exposure to exogenous estrogens during fetal/neonatal life can lead to reproductive disorders in the male. However, the estrogen receptor (ER)-mediated processes involved in the regulation of male reproduction during fetal and neonatal development are still largely unclear. We previously reported that ER beta deficiency affects gametogenesis in mice but changes neither the number nor the differentiated functions of fetal Leydig cells. We show here that ER alpha-deficient mice (ER alpha(-/-)) display higher levels of testicular testosterone secretion than wild-type mice from fetal d 13.5 onwards. This results from higher levels of steroidogenic activity per fetal Leydig cell, as indicated by the hypertrophy of these cells and the higher levels of mRNA for StAR, P450c17 and P450scc in testis, for a similar number of Leydig cells. Because LH is not produced on fetal d 13.5 and because no change in plasma LH concentration was observed in 2-d-old ER alpha-deficient mice, LH is probably not involved in the effects of estrogens on testicular steroidogenesis in fetal and early neonatal Leydig cells. Furthermore, inactivation of ER beta did not change the effect of ER alpha inactivation on steroidogenesis. Lastly, in an organ culture system, 1 mu M diethylstilbestrol decreased the testosterone secretion of wild-type fetal and neonatal testes but not of ER alpha(-/-) testes. Thus, this study shows that endogenous estrogens physiologically inhibit steroidogenesis via ER alpha by acting directly on the testis early in fetal and neonatal development.