Androgens impair β-cell function in a mouse model of polycystic ovary syndrome by activating endoplasmic reticulum stress.

Background Androgens excess results in endoplasmic reticulum (ER) stress, which is an important cause of β cells dysfunction. Here, we investigated the molecular regulation of androgens excess, ER stress, and β-cell function in polycystic ovary syndrome (PCOS). Methods PCOS mouse model was established by injection of dehydroepiandrosterone (DHEA). Primary cultured mouse islets were used to detect testosterone (TE)-induced ER stress. The response of ER stress, apoptosis, and hyperinsulinemia were analyzed in INS-1 cells with or without TE exposure. Androgen receptor (AR) antagonist and ER stress inhibitor treatment was performed to evaluate the role of TE in ER stress and proinsulin secretion of PCOS mice. Results PCOS mice had higher ER stress in islets. TE exposure induced ER stress and apoptosis significantly through sustaining insulin overexpression in β cells, which in turn impaired proinsulin maturation and secretion. Blocking this process could significantly relieve ER stress and apoptosis and improve insulin homeostasis. Conclusion ER stress activated by androgens excess in PCOS contributes to β cell dysfunction and hyperinsulinemia.