内科学
内分泌学
卵泡期
卵泡闭锁
雄激素受体
生物
雄激素
排卵
卵泡
促卵泡激素
激素
促黄体激素
医学
前列腺癌
癌症
作者
Aritro Sen,Hen Prizant,Allison Light,Anindita Biswas,Emily Hayes,Hojoon Lee,David H. Barad,Norbert Gleicher,Stephen R. Hammes
出处
期刊:Proceedings of the National Academy of Sciences
日期:2014-02-10
卷期号:111 (8): 3008-3013
被引量:219
标识
DOI:10.1073/pnas.1318978111
摘要
Although androgen excess is considered detrimental to women's health and fertility, global and ovarian granulosa cell-specific androgen-receptor (AR) knockout mouse models have been used to show that androgen actions through ARs are actually necessary for normal ovarian function and female fertility. Here we describe two AR-mediated pathways in granulosa cells that regulate ovarian follicular development and therefore female fertility. First, we show that androgens attenuate follicular atresia through nuclear and extranuclear signaling pathways by enhancing expression of the microRNA (miR) miR-125b, which in turn suppresses proapoptotic protein expression. Second, we demonstrate that, independent of transcription, androgens enhance follicle-stimulating hormone (FSH) receptor expression, which then augments FSH-mediated follicle growth and development. Interestingly, we find that the scaffold molecule paxillin regulates both processes, making it a critical regulator of AR actions in the ovary. Finally, we report that low doses of exogenous androgens enhance gonadotropin-induced ovulation in mice, further demonstrating the critical role that androgens play in follicular development and fertility. These data may explain reported positive effects of androgens on ovulation rates in women with diminished ovarian reserve. Furthermore, this study demonstrates mechanisms that might contribute to the unregulated follicle growth seen in diseases of excess androgens such as polycystic ovary syndrome.
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