IRS2 depletion inhibits cell proliferation and decreases hormone secretion in mouse granulosa cells

The Journal of Reproduction and Development
Lanjie LeiLei Yang

Abstract

Insulin receptor substrate 2 (IRS2) is a component of the insulin/insulin-like growth factor 1 (IGF1) signaling cascade, which plays an important role in mouse hypothalamic and ovarian functions. The present study was conducted to investigate the role of IRS2 in steroidogenesis, apoptosis, cell cycle and proliferation in mouse granulosa cells (GCs). Flow cytometry and CCK8 assay showed that IRS2 knockdown inhibited cell proliferation, reduced cell viability, and increased apoptosis in GCs. The study also revealed that the expression of Cyclin A1, Cyclin B1 and Bcl2 was downregulated, while the expression of Bax, Cyclin D1 and Cyclin D2 was upregulated. ELISA analysis showed that IRS2 knockdown decreased the concentrations of estradiol (E2) and progesterone (P4), which was further validated by the decreased expression of Star, Cyp11a1, and Cyp19a1. Moreover, IRS2 knockdown altered the expression of Has2 and Ptgs2, which are essential for folliculogenesis. In addition, we found that IRS2-mediated cell viability and hormone secretion are dependent on the PI3K/AKT signaling pathway. Collectively, this study demonstrated that IRS2 plays an important role in the regulation of cell proliferation and steroidogenesis in mouse GCs via th...Continue Reading

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Citations

Feb 14, 2020·The Journal of Reproduction and Development·Lei YangDenggang Fu
Aug 14, 2019·The Journal of Reproduction and Development·Lanjie LeiLei Yang
Feb 12, 2021·Journal of Cellular and Molecular Medicine·Xiangming XuDuannuo Song
Feb 19, 2021·Molecular and Cellular Biochemistry·Deborah MolehinKevin Pruitt
May 8, 2020·Molecular and Cellular Endocrinology·Jiahui HuFenglei Chen
Jul 2, 2020·Molecular and Cellular Endocrinology·Natalie A DeWittAmanda N Kallen

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Methods Mentioned

BETA
transfection
PCR
electrophoresis
ELISA
flow cytometry

Software Mentioned

Quant
SPSS
Studio 6 Flex
ModFit LT
ImageJ

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