Adiponectin increases insulin-like growth factor I-induced progesterone and estradiol secretion in human granulosa cells

Fertil Steril. 2009 Dec;92(6):1988-96. doi: 10.1016/j.fertnstert.2008.09.008. Epub 2008 Dec 10.

Abstract

Objective: To identify adiponectin and its receptors (AdipoR1 and AdipoR2) in human granulosa cells (GC) and to study the effects of recombinant human adiponectin on P and E(2) secretion from these cells.

Design: The effects of recombinant human adiponectin on the secretion of P and E(2) by cultured human GCs were investigated.

Setting: Academic institutions.

Patient(s): Seventeen infertile and healthy women undergoing IVF.

Intervention(s): Primary human GC cultures stimulated with human recombinant adiponectin (5 microg/mL).

Main outcome measure(s): Determination of messenger RNA (mRNA) and protein expression of adiponectin and its receptors AdipoR1 and AdipoR2 in fresh human GCs by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot, respectively. Measurement of P and E(2) levels in the conditioned media by RIA and determination of cell proliferation by tritied thymidine incorporation.

Result(s): Human GCs express adiponectin receptors AdipoR1 and AdipoR2 but not adiponectin. In primary human GCs, adiponectin increases P and E(2) secretion in response to insulin-like growth factor I (IGF-I). This was associated with an increase in the p450 aromatase protein level but not those of p450scc, 3 beta HSD, or StAR. Adiponectin treatment does not affect IGF-1-induced cell proliferation and basal steroidogenesis (no IGF-1 or FSH stimulation). Adiponectin rapidly stimulates MAPK ERK1/2 and p38 phosphorylation in primary human GCs.

Conclusion(s): Adiponectin receptors AdipoR1 and AdipoR2, but not adiponectin, are present in human GCs. Adiponectin increases IGF-1-induced P and E(2) secretion in primary human GCs.

MeSH terms

  • Adiponectin / blood
  • Adiponectin / pharmacology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Estradiol / metabolism*
  • Female
  • Fertilization in Vitro
  • Follicle Stimulating Hormone / metabolism
  • Follicle Stimulating Hormone / pharmacology
  • Follicular Fluid / metabolism
  • Gene Expression / physiology
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism*
  • Humans
  • Infertility, Female / metabolism*
  • Infertility, Female / physiopathology
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Oocyte Retrieval
  • Progesterone / metabolism*
  • Receptors, Adiponectin / genetics
  • Receptors, Adiponectin / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • ADIPOQ protein, human
  • ADIPOR1 protein, human
  • ADIPOR2 protein, human
  • Adiponectin
  • Receptors, Adiponectin
  • Recombinant Proteins
  • Progesterone
  • Estradiol
  • Insulin-Like Growth Factor I
  • Follicle Stimulating Hormone