title: High concentration of insulin promotes apoptosis of primary cultured rat ovarian granulosa cells via its increase in extracellular HMGB1.
abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. Insulin resistance/hyperinsulinemia is a prevalent finding in women with PCOS, which indicates that insulin resistance/hyperinsulinemia may be an important player in the pathogenesis of the PCOS. However, the underlying mechanism of insulin resistance/hyperinsulinemia on the pathogenesis of the PCOS remains elusive. In this study, we found an increased high-mobility group box 1 (HMGB1) in the serum from women with PCOS having insulin resistance/hyperinsulinemia. Furthermore, we discovered that high concentration of insulin, which mimics insulin resistance model, promoted apoptosis in primary cultured rat ovarian granulosa cells (GCs) via its effect on the increase in extracellular HMGB1. Our data presented the first evidence that increased HMGB1 induced by insulin resistance/hyperinsulinemia promoted apoptosis of ovarian GCs, which provided new molecular basis for the PCOS pathogenesis.
authors.affiliation: Gynecology Department, Shanghai Traditional Chinese Medicine Hospital, Shanghai, People's Republic of China shzyynxr@163.com.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Ni
authors.affiliation: Gynecology Department, Shanghai Traditional Chinese Medicine Hospital, Shanghai, People's Republic of China.
authors.forename: Zhou-Jun
authors.initials: ZJ
authors.lastname: Sun
authors.affiliation: Gynecology Department, Shanghai Traditional Chinese Medicine Hospital, Shanghai, People's Republic of China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Hu
authors.affiliation: Gynecology Department, Shanghai Traditional Chinese Medicine Hospital, Shanghai, People's Republic of China.
authors.forename: Rong-Hui
authors.initials: RH
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024243:HMGB1 Protein / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000633:toxicity*; D007333:Insulin Resistance; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000503:physiopathology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C104200:Hbp1 protein, rat; D007328:Insulin
keywords: apoptosis; high-mobility group box 1(HMGB1); insulin resistance/hyperinsulinemia; ovarian granulosa cells; polycystic ovary syndrome (PCOS)