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OCT4在雌性小鼠促卵泡激素诱导的颗粒细胞生长调控中的作用

Role of OCT4 in the Regulation of FSH-Induced Granulosa Cells Growth in Female Mice.

作者信息

Heng Dai, Wang Qiaozhi, Ma Xiaoshu, Tian Ye, Xu Kaili, Weng Xuechun, Hu Xusong, Liu Wenbo, Zhang Cheng

机构信息

College of Life Science, Capital Normal University, Beijing, China.

出版信息

Front Endocrinol (Lausanne). 2020 Jan 10;10:915. doi: 10.3389/fendo.2019.00915. eCollection 2019.

Abstract

As a member of the POU (Pit-Oct-Unc) transcription factor family, OCT4 (Octamer-binding transcription factor 4) is associated with the cellular proliferative. However, the roles of OCT4 in regulating the transition from preantral follicle to early antral follicle are still remains unclear. To evaluate the effect of OCT4 on cellular development in ovary, mice were injected with eCG or granulosa cells were co-cultured with FSH . The results showed that eCG up-regulated ovarian OCT4 expression. Meanwhile, OCT4 expression in granulosa cells was also up-regulated by FSH, and knockdown of OCT4 by siRNA significantly decreased FSH-induced cellular viability. Moreover, gonadotropin increased p-GSK3β (Glycogen synthase kinase 3-beta) level, β-catenin expression and its translocation to nuclear in ovarian cells. In addition, the inhibition of GSK3β activity by CT99021 significantly increased the expression of β-catenin and OCT4 in granulosa cells. And knockdown β-catenin by siRNA dramatically abolished FSH-induced OCT4 expression and cellular development. Furthermore, FSH-induced the phosphorylation of GSK3β, expression of β-catenin and OCT4, and translocation of β-catenin were mediated by the PI3K/Akt pathway. Taken together, the present study demonstrates that FSH regulated OCT4 expression via GSK3β/β-catenin pathway, which was mediated by the PI3K/Akt pathway. And these regulations are involved in ovarian cell development.

摘要

作为POU(Pit-Oct-Unc)转录因子家族的一员,OCT4(八聚体结合转录因子4)与细胞增殖相关。然而,OCT4在调节初级卵泡向早期窦状卵泡转变中的作用仍不清楚。为了评估OCT4对卵巢细胞发育的影响,给小鼠注射eCG或使颗粒细胞与FSH共培养。结果显示,eCG上调了卵巢OCT4的表达。同时,FSH也上调了颗粒细胞中OCT4的表达,并且通过siRNA敲低OCT4显著降低了FSH诱导的细胞活力。此外,促性腺激素增加了卵巢细胞中p-GSK3β(糖原合酶激酶3-β)水平、β-连环蛋白的表达及其向细胞核的转位。另外,CT99021对GSK3β活性的抑制显著增加了颗粒细胞中β-连环蛋白和OCT4的表达。通过siRNA敲低β-连环蛋白显著消除了FSH诱导的OCT4表达和细胞发育。此外,FSH诱导的GSK3β磷酸化、β-连环蛋白和OCT4的表达以及β-连环蛋白的转位是由PI3K/Akt途径介导的。综上所述,本研究表明FSH通过GSK3β/β-连环蛋白途径调节OCT4表达,该途径由PI3K/Akt途径介导。并且这些调节参与了卵巢细胞发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4960/6966609/412df0386d4a/fendo-10-00915-g0001.jpg

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