Role of adiponectin/peroxisome proliferator-activated receptor alpha signaling in human chorionic gonadotropin-induced estradiol synthesis in human luteinized granulosa cells

Mol Cell Endocrinol. 2019 Aug 1:493:110450. doi: 10.1016/j.mce.2019.110450. Epub 2019 May 19.

Abstract

Impaired steroid production in polycystic ovary syndrome (PCOS) may result from adiponectin system dysfunction. However, adiponectin's role in ovulatory dysfunction remains unclear. We aimed to determine whether human chorionic gonadotropin (hCG) and adiponectin affect progesterone and estradiol secretion by granulosa cells (GCs) from overweight or obese women with PCOS or normal ovulation. ADIPOR2 expression was higher in hCG-treated GCs from PCOS patients than in those from normovulatory women. hCG may upregulate ADIPOR2 expression through cAMP/PKA signaling in GCs. GCs from both groups expressed PPARA. Estradiol levels were lower in hCG + adiponectin-treated GCs from PCOS patients than in those from normovulatory women. hCG + adiponectin decreased P450 aromatase expression through adiponectin/PPARα signaling in GCs. Adiponectin downregulates hCG-induced estradiol levels in GCs from overweight or obese women through gonadotropin-adiponectin crosstalk. Changes in gonadotropin and adiponectin signaling in the ovarian microenvironment may improve symptoms in women with PCOS.

Keywords: Adiponectin; Luteinized granulosa cells; Peroxisome proliferator-activated receptor alpha; Polycystic ovary syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / metabolism*
  • Adult
  • Case-Control Studies
  • Chorionic Gonadotropin / metabolism*
  • Estradiol / metabolism*
  • Female
  • Granulosa Cells / metabolism
  • Humans
  • Obesity / complications
  • Obesity / genetics
  • Obesity / metabolism*
  • Overweight / complications
  • Overweight / genetics
  • Overweight / metabolism*
  • PPAR alpha / metabolism*
  • Polycystic Ovary Syndrome / metabolism*
  • Receptors, Adiponectin / genetics
  • Signal Transduction / drug effects
  • Up-Regulation
  • Young Adult

Substances

  • ADIPOR2 protein, human
  • Adiponectin
  • Chorionic Gonadotropin
  • PPAR alpha
  • PPARA protein, human
  • Receptors, Adiponectin
  • Estradiol