論文 - 詳細
| RRC ID | 72471 |
|---|---|
| 著者 | Sen A, Prizant H, Light A, Biswas A, Hayes E, Lee HJ, Barad D, Gleicher N, Hammes SR. |
| タイトル | Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
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. |
| 巻・号 | 111(8) |
| ページ | 3008-13 |
| 公開日 | 2014-2-25 |
| DOI | 10.1073/pnas.1318978111 |
| PII | 1318978111 |
| PMID | 24516121 |
| PMC | PMC3939860 |
| MeSH | Analysis of Variance Animals Blotting, Western Chromatin Immunoprecipitation Female Flow Cytometry Follicular Atresia / metabolism Gene Expression Regulation / drug effects Gene Expression Regulation / physiology* Gene Knockdown Techniques Granulosa Cells / metabolism In Situ Nick-End Labeling Mice Mice, Inbred C57BL MicroRNAs / antagonists & inhibitors MicroRNAs / metabolism* Ovarian Follicle / drug effects Ovarian Follicle / growth & development* Ovarian Follicle / metabolism Paxillin / genetics Paxillin / metabolism Receptors, FSH / metabolism* Testosterone / metabolism* Testosterone / pharmacology |
| IF | 9.412 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 25 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| ヒト・動物細胞 | KGN(RCB1154) |