Notch signalling regulates steroidogenesis in mouse ovarian granulosa cells
Notch signalling regulates steroidogenesis in mouse ovarian granulosa cells
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Notch信号调节小鼠卵巢颗粒细胞的类固醇生成
DOI：
10.1071/rd18281
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Zhang Chunping
中科院分区：
文献类型：
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作者：
Wang Yishu;Lu Enhang;Bao Riqiang;Xu Ping;Feng Fen;Wen Weihui;Dong Qiming;Hu Chuan;Xiao Li;Tang Min;Li Gang;Wang Jing;Zhang Chunping
哺乳动物卵巢Notch信号通路调控颗粒细胞增殖。然而，Notch信号在类固醇生成中的作用尚不清楚。本研究通过体外培养小鼠卵巢腔前卵泡颗粒细胞，通过Notch信号的过表达、敲低和抑制，观察Notch信号对类固醇生成的影响。Notch信号的激活降低了孕酮和雌激素的分泌。相反，抑制Notch信号会增加孕酮和雌激素的分泌。甾体生成相关酶基因的表达，包括3β-羟基类固醇脱氢酶、p450胆固醇侧链裂解酶和芳香化酶，在Notch信号刺激后被抑制。在Notch信号刺激后，上游转录因子，包括甾体生成因子1 （SF1）、Wilms ' tumor 1 （Wt1）、gata结合蛋白4 （Gata4）和Gata6的表达也被抑制。白细胞介素(IL)-6的产生与Notch信号正相关，与这些转录因子和酶的表达负相关。综上所述，Notch信号通路通过影响上游转录因子SF1、Wt1、Gata4和Gata6以及下游甾体相关酶的表达来调控孕酮和雌激素的分泌。IL-6可能直接受到Notch信号的调控，参与了这一过程。我们的发现增加了对Notch信号在哺乳动物卵巢中多种功能的理解。
The Notch signalling pathway in the mammalian ovary regulates granulosa cell proliferation. However, the effects of Notch signalling on steroidogenesis are unclear. In this study we cultured mouse ovarian granulosa cells from preantral follicles in vitro and observed the effect of Notch signalling on steroidogenesis through overexpression, knockdown and inhibition of Notch signalling. Activation of Notch signalling decreased progesterone and oestrogen secretion. In contrast, inhibition of Notch signalling increased the production of progesterone and oestrogen. Expression of the genes for steroidogenic-related enzymes, including 3β-hydroxysteroid dehydrogenase, p450 cholesterol side-chain cleavage enzyme and aromatase, was repressed after stimulation of Notch signalling. The expression of upstream transcription factors, including steroidogenic factor 1 (SF1), Wilms’ tumour 1 (Wt1), GATA-binding protein 4 (Gata4) and Gata6, was also inhibited after stimulation of Notch signalling. Production of interleukin (IL)-6 was positively correlated with Notch signalling and negatively correlated with the expression of these transcription factors and enzymes. In conclusion, Notch signalling regulated progesterone and oestrogen secretion by affecting the expression of upstream transcription factors SF1, Wt1, Gata4 and Gata6, as well as downstream steroidogenic-related enzymes. IL-6, which may be regulated directly by Notch signalling, may contribute to this process. Our findings add to the understanding of the diverse functions of Notch signalling in the mammalian ovary.