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Human granulosa cells: insulin and insulin-like growth factor-1 receptors and aromatase expression modulation by

Isabela Piva Fuhrmeister1, Gisele Branchini, Anita M Pimentel

  • 1Núcleo de Reprodução Humana, Hospital Moinhos de Vento, Porto Alegre, Brazil.

Gynecologic and Obstetric Investigation
|March 8, 2014
PubMed
Abstract

Insights

Metformin directly impacts gene expression of insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R), and aromatase in ovarian granulosa cells. This suggests metformin

Area of Science:

  • Reproductive Endocrinology
  • Molecular Biology
  • Pharmacology

Background:

  • Granulosa cells are key ovarian steroid producers.
  • Metformin demonstrates significant effects on ovarian function, independent of metabolic improvements.
  • Understanding metformin's impact on ovarian gene expression is crucial.

Purpose of the Study:

  • To investigate the effects of metformin and insulin on the gene and protein expression of insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R), and aromatase in human granulosa cells.
  • To elucidate the molecular mechanisms underlying metformin's action in the ovary.

Main Methods:

  • Luteinized granulosa cells were obtained from 27 patients undergoing in vitro fertilization.
  • Cells were cultured and treated with metformin and/or insulin for specified durations.
  • Gene (mRNA) and protein expression levels of IR, IGF1R, and aromatase were analyzed.

Main Results:

  • Metformin significantly upregulated the mRNA expression of IR and IGF1R.
  • Insulin did not affect IR or IGF1R mRNA levels.
  • Metformin, combined with insulin, significantly reduced aromatase mRNA expression.
  • No significant differences were observed in IGF1R and aromatase protein expression; IR protein was undetectable.

Conclusions:

  • Metformin exerts a direct influence on the gene expression of IGF1R, IR, and aromatase in granulosa cells.
  • These findings highlight a potential molecular pathway for metformin's ovarian effects.
  • Further research is warranted to explore the roles of IGF1R, IR, and aromatase in ovarian physiology and metformin's therapeutic potential.

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