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
Joint Program of Nanchang University and Queen Mary University of London, School of Medicine, Nanchang University, #461 Bayi Avenue, Nanchang, Jiangxi 330006, PR China.
Second Clinical College, School of Medicine, Nanchang University, #461 Bayi Avenue, Nanchang, Jiangxi 330006, PR China.
Reprod Fertil Dev. 2019 May;31(6):1091-1103. doi: 10.1071/RD18281.
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 invitro 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.
哺乳动物卵巢中的Notch信号通路调节颗粒细胞增殖。然而，Notch信号对类固醇生成的影响尚不清楚。在本研究中，我们体外培养来自窦前卵泡的小鼠卵巢颗粒细胞，并通过Notch信号的过表达、敲低和抑制来观察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，Notch信号的抑制增加了孕酮和雌激素的产生。在Notch信号刺激后，包括3β-羟基类固醇脱氢酶、细胞色素P450胆固醇侧链裂解酶和芳香化酶在内的类固醇生成相关酶的基因表达受到抑制。在Notch信号刺激后，包括类固醇生成因子1（SF1）、威尔姆斯瘤1（Wt1）、GATA结合蛋白4（Gata4）和Gata6在内的上游转录因子的表达也受到抑制。白细胞介素（IL）-6的产生与Notch信号呈正相关，与这些转录因子和酶的表达呈负相关。总之，Notch信号通过影响上游转录因子SF1、Wt1、Gata4和Gata6以及下游类固醇生成相关酶的表达来调节孕酮和雌激素的分泌。可能受Notch信号直接调节的IL-6可能参与了这一过程。我们的发现有助于加深对Notch信号在哺乳动物卵巢中多种功能的理解。
