Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1α in mouse granulosa cells.
Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1α in mouse granulosa cells.
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卵泡刺激素的施用通过上调小鼠颗粒细胞中的 HIF-1α 诱导自噬
DOI：
10.1038/cddis.2017.371
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发表时间：
2017-08-17
影响因子：
9
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Zhou J;Yao W;Li C;Wu W;Li Q;Liu H
最近的研究报道了自噬在卵泡发育中的重要作用。然而，潜在的分子机制仍然难以捉摸。在本研究中，我们研究了卵泡刺激素(FSH)对小鼠颗粒细胞(MGCS)的影响。结果表明，自噬是由FSH诱导的，FSH被认为是调节卵泡发育和颗粒细胞(GC)增殖的主要激素。哺乳动物靶标雷帕霉素(MTOR)是自噬的主要调节因子，在MGC自噬过程中被抑制。此外，mTOR激动剂MHY1485通过激活mTOR显著抑制自噬信号。促卵泡激素治疗后缺氧诱导因子1-α(HIF-1α)表达增加。阻断低氧诱导因子1-α可减弱自噬信号。在体外，CoCl2诱导的低氧促进细胞自噬，并在FSH存在的情况下影响Beclin1和bcl2/腺病毒E1B相互作用蛋白3(Bnip3)的表达。敲除Beclin1和Bnip3基因可抑制mGCS中的自噬信号。此外，我们的体内研究表明，在有效抑制氯喹自噬后，FSH诱导的体重增加明显减少，这与PINK1-Parkin途径的有丝分裂吞噬过程不完整、细胞周期延迟和细胞增殖率降低有关。此外，氯喹处理降低了抑制素α亚基，但增强了3β-羟基类固醇脱氢酶的表达。阻断自噬可显著降低FSH刺激后有腔卵泡和排卵前卵泡的比例。综上所述，我们的结果表明，卵泡刺激素通过HIF-1α诱导MGC自噬信号。此外，我们的结果提供了FSH诱导的自噬与卵泡发育和闭锁有关的证据。
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy. Moreover, MHY1485 (an agonist of mTOR) significantly suppressed autophagy signaling by activating mTOR. The expression of hypoxia-inducible factor 1-alpha (HIF-1α) was increased after FSH treatment. Blocking hypoxia-inducible factor 1-alpha attenuated autophagy signaling. In vitro, CoCl 2-induced hypoxia enhanced cell autophagy and affected the expression of beclin1 and BCL2/adenovirus E1B interacting protein 3 (Bnip3) in the presence of FSH. Knockdown of beclin1 and Bnip3 suppressed autophagy signaling in MGCs. Furthermore, our in vivo study demonstrated that the FSH-induced increase in weight was significantly reduced after effectively inhibiting autophagy with chloroquine, which was correlated with incomplete mitophagy process through the PINK1-Parkin pathway, delayed cell cycle, and reduced cell proliferation rate. In addition, chloroquine treatment decreased inhibin alpha subunit, but enhanced the expression of 3 beta-hydroxysteroid dehydrogenase. Blocking autophagy resulted in a significantly lower percentage of antral and preovulatory follicles after FSH stimulation. In conclusion, our results indicate that FSH induces autophagy signaling in MGCs via HIF-1α. In addition, our results provide evidence that autophagy induced by FSH is related to follicle development and atresia.
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影响因子：
44.1
作者：
Huang, Yan;Hua, Keqin;Feng, Youji
通讯作者：
Feng, Youji
影响因子：
4.8
作者：
Anand, Paras K.;Tait, Stephen W. G.;Kanneganti, Thirumala-Devi
通讯作者：
Kanneganti, Thirumala-Devi
影响因子：
3.8
作者：
Gawriluk, Thomas R.;Hale, Amber N.;Rucker, Edmund B., III
通讯作者：
Rucker, Edmund B., III
DOI：
10.1051/rnd:19960203
发表时间：
1996-01-01
期刊：
REPRODUCTION NUTRITION DEVELOPMENT
影响因子：
--
作者：
DHerde, K;DePrest, B;Roels, F
通讯作者：
Roels, F
影响因子：
7.2
作者：
Hulas-Stasiak, Monika;Gawron, Antoni
通讯作者：
Gawron, Antoni