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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.

Author information

1
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.
2
Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China.
3
Qilu Hospital of Shandong University, Jinan, China.

Abstract

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.

PMID:
24799026
DOI:
10.1055/s-0034-1374588
[Indexed for MEDLINE]

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