Melatonin induces progesterone production in human granulosalutein cells through upregulation of StAR expression
Melatonin induces progesterone production in human granulosalutein cells through upregulation of StAR expression
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褪黑激素通过上调 StAR 表达诱导人颗粒黄体素细胞产生黄体酮
DOI：
10.18632/aging.102367
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发表时间：
2019-10-31
期刊：
影响因子：
5.2
通讯作者：
Sun, Ying-Pu
中科院分区：
文献类型：
--
作者：
Fang, Lanlan;Li, Yiran;Sun, Ying-Pu
类固醇生成急性调节蛋白（星星）介导卵巢类固醇生成和孕酮（P4）合成的限速步骤。褪黑激素及其受体在人类颗粒细胞中表达，并已被证明影响基础P4的产生。然而，以前的研究解决褪黑激素的调节星星表达及其对P4分泌的影响产生了矛盾的结果。在这里，我们证明，褪黑激素上调星星表达的人颗粒黄体（hGL）细胞从妇女接受体外受精（IVF）的原代培养。使用药理学抑制剂，我们表明，褪黑激素对星星表达的刺激作用是通过MT 1和MT 2褪黑激素受体介导的。褪黑激素暴露激活PI 3 K/AKT信号通路，其抑制减弱褪黑激素对星星表达的刺激作用。此外，siRNA介导的星星敲低可消除褪黑激素诱导的P4产生。重要的是，临床分析表明，人卵泡液中的褪黑激素水平与血清中的P4水平正相关。通过说明褪黑激素在调节星星表达和hGL细胞中P4产生中的潜在生理作用，我们的研究结果可能有助于改善目前用于治疗临床不孕症的策略。
Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in ovarian steroidogenesis and progesterone (P4) synthesis. Melatonin and its receptors are expressed in human granulosa cells, and have been shown to influence basal P4 production. However, previous studies addressing the regulation of StAR expression by melatonin and its impact on P4 secretion yielded contradictory results. Here, we demonstrate that melatonin upregulates StAR expression in primary cultures of human granulosa-lutein (hGL) cells obtained from women undergoing in vitro fertilization (IVF). Using pharmacological inhibitors, we show that the stimulatory effect of melatonin on StAR expression is mediated via both MT1 and MT2 melatonin receptors. Melatonin exposure activates the PI3K/AKT signaling pathway and its inhibition attenuates the stimulatory effect of melatonin on StAR expression. Moreover, siRNA-mediated knockdown of StAR abolishes melatonin-induced P4 production. Importantly, clinical analyses demonstrate that melatonin levels in human follicular fluid are positively correlated with P4 levels in serum. By illustrating the potential physiological role of melatonin in the regulation of StAR expression and P4 production in hGL cells, our results may serve to improve current strategies used to treat clinical infertility.