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Metabolic actions of insulin in ovarian granulosa cells were unaffected by hyperandrogenism

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Abstract

Polycystic ovary syndrome (PCOS) patients have intra-ovarian hyperandrogenism and granulosa cells (GCs) from PCOS patients have impaired insulin-dependent glucose metabolism and insulin resistance. The purpose of this study is to determine whether excess androgen affects glucose metabolism and induces insulin resistance of GCs. We firstly explored the insulin metabolic signaling pathway and glucose metabolism in cultured GCs. The Akt phosphorylation and lactate production were increased after insulin treatment. Pre-treatment with PI3-K inhibitor attenuated insulin-induced phosphorylation of Akt and lactate accumulation. However, after treating GCs with different concentrations of testosterone for 5 days, insulin-induced phosphorylation of Akt and lactate production showed no significant change comparing with those of control cells. Finally, mRNA expression of insulin signaling mediators including INSR, IRS-1, IRS-2, and GLUT-4 in GCs was also not significantly altered after testosterone treatment. In conclusion, insulin activates PI3-K/Akt signaling pathway and promotes lactate production in ovarian GCs, but high androgen exerted no obvious influence on insulin signaling pathway and metabolic effect in GCs, suggesting that metabolic actions of insulin in ovarian GCs were unaffected by hyperandrogenism directly.

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Acknowledgments

This work was supported by the National Basic Research Program of China (973 program, 2012CB944700); National Natural Science Foundation of China (81200419); Shandong Province Excellent Young and Middle-Aged Scientists Research Awards Fund (BS2013YY012); Key Program for Basic Research of the Science and Technology Commission of Shanghai Municipality, China (12JC1405800); China Postdoctoral Science Foundation Funded Project (2012M511522, 2013T60677); and Postdoctoral Innovation Foundation of Shandong Province (201203043). The authors thank all of their colleagues for technical support.

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Authors and Affiliations

  1. Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, 324 Jingwu Road, Jinan, 250021, People’s Republic of China

    Shidou Zhao, Yuqian Cui, Wenting Wang, Yingying Qin, Li You & Zi-Jiang Chen

  2. The Chinese University of Hong Kong-Shandong University Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China

    Shidou Zhao & Wai-Yee Chan

  3. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

    Haijing Xu, Yun Sun & Zi-Jiang Chen

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  1. Shidou Zhao
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Zhao, S., Xu, H., Cui, Y. et al. Metabolic actions of insulin in ovarian granulosa cells were unaffected by hyperandrogenism. Endocrine 53, 823–830 (2016). https://doi.org/10.1007/s12020-016-0949-y

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