Rev-erbα regulates circadian rhythms and StAR expression in rat granulosa cells as identified by the agonist GSK4112
Rev-erbα regulates circadian rhythms and StAR expression in rat granulosa cells as identified by the agonist GSK4112
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DOI：
10.1016/j.bbrc.2012.02.164
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发表时间：
2012-04-06
影响因子：
3.1
通讯作者：
Hattori, Masa-aki
中科院分区：
文献类型：
--
作者：
Chen, Huatao;Chu, Guiyan;Hattori, Masa-aki
Rev - erbα基因被视为一种生物钟基因以及受生物钟调控的基因，它以一种微妙的方式调节生物钟转录/翻译回路。在此，我们首先利用添加了促卵泡激素（FSH）的Per2启动子活性实时监测系统，检测了来自窦卵泡的成熟颗粒细胞中的生物钟振荡情况。然后我们使用Rev - erbα的激动剂配体GSK4112来研究Rev - erbα的功能。GSK4112处理显著降低了Per2 - dLuc的振幅，并诱导Per2振荡相位提前移动。GSK4112显著抑制Bmal1 mRNA的表达，然而它确实以剂量依赖的方式刺激StAR mRNA的表达。我们的数据首次表明了Rev - erbα在大鼠颗粒细胞类固醇生物合成中的功能，并提示Rev - erbα可能在大鼠卵巢中协调生物钟节律和代谢。（C）2012爱思唯尔公司。保留所有权利。
The Rev-erb alpha gene is regarded as a circadian clock gene and clock-regulated gene which regulates the circadian transcriptional/translational loop in a subtle way. Here, we first detected the circadian oscillation in mature granulosa cells from antral follicles using a real-time monitoring system of Per2 promoter activity with the addition of FSH. Then we used GSK4112, an agonist ligand of Rev-erb alpha, to investigate the function of Rev-erb alpha. GSK4112 treatment significantly reduced the Per2-dLuc amplitude and induced the Per2 oscillation phase advance shift. GSK4112 significantly inhibited Bmal1 mRNA expression, whereas it did clearly stimulate expression of StAR mRNA in a dose-dependent manner. Our data are the first to show the Rev-erb alpha function in the steroid biosynthesis of rat granulosa cells, and to suggest that Rev-erb alpha may coordinate circadian rhythm and metabolism in rat ovaries. (C) 2012 Elsevier Inc. All rights reserved.