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Horm Metab Res. 2014 Jul;46(8):574-80. doi: 10.1055/s-0034-1374588. Epub 2014 May 5.

Activation of eIF2α signaling cascade is associated with testosterone-induced cell apoptosis in INS-1 cells.

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Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory for Assisted -Reproduction and Reproductive Genetics, Shanghai, China.
Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China.
Qilu Hospital of Shandong University, Jinan, China.


Hyperandrogenemia is associated with insulin resistance and type 2 diabetes in women with polycystic ovary syndrome raising the possibility that androgen receptor signaling pathway plays an important role in the development and progression of β-cell dysfunction. Testosterone is the major circulating androgen in women. In this study, we investigated the effect of testosterone on INS-1 cells to find whether excess androgen could produce endoplasmic reticulum (ER) stress thereby contributing to β-cell dysfunction. The role of testosterone in INS-1 cell apoptosis was detected by flow cytometry and electron microscopy. Expression of BIP, ATF4, and CHOP were assessed by RT-PCR and Western blot. Testosterone/AR could not only initiate cell apoptosis but also induce the activation of eukaryotic initiation factor 2 alpha (eIF2α) cascades in INS-1 cells. Treatment of ER stress inhibitor or flutamide (AR inhibitor) could inhibit testosterone-induced cell apoptosis and CHOP expression. These results suggest that testosterone/AR pathway caused INS-1 cell apoptosis was at least in part through eIF2α/CHOP cascades.

[Indexed for MEDLINE]

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