High concentration of insulin promotes apoptosis of primary cultured rat ovarian granulosa cells via its increase in extracellular HMGB1

Reprod Sci. 2015 Mar;22(3):271-7. doi: 10.1177/1933719114549852. Epub 2014 Sep 16.

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.

Keywords: apoptosis; high-mobility group box 1(HMGB1); insulin resistance/hyperinsulinemia; ovarian granulosa cells; polycystic ovary syndrome (PCOS).

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Case-Control Studies
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Granulosa Cells / drug effects*
  • Granulosa Cells / metabolism
  • Granulosa Cells / pathology
  • HMGB1 Protein / blood
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism*
  • Humans
  • Insulin / toxicity*
  • Insulin Resistance
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / physiopathology
  • RNA Interference
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Time Factors
  • Transfection
  • Up-Regulation

Substances

  • HMGB1 Protein
  • HMGB1 protein, human
  • Hbp1 protein, rat
  • Insulin