Growth differential factor-9 inhibits testosterone production in mouse theca interstitial cells

Fertil Steril. 2013 Nov;100(5):1444-50. doi: 10.1016/j.fertnstert.2013.07.200. Epub 2013 Aug 15.

Abstract

Objective: To explore the effect of growth differential factor-9 (GDF-9) alone on cell proliferation, cell viability, steroidogenesis, and hormone-stimulated gene expression in cultured mouse theca interstitial cells.

Design: Basic research.

Setting: University hospital.

Animal(s): Immature 3- to 4-week-old SPF KM mice obtained from the Laboratory Animal Center of Sun Yat-Sen University.

Intervention(s): Addition of GDF-9 at different dosages to primary culture of mouse theca interstitial cells.

Main outcome measure(s): Cell number, cell viability, progesterone and testosterone levels, and hormone-stimulated gene mRNA abundance.

Result(s): Growth differential factor-9 mildly increased the number of mouse theca interstitial cells and cell viability in a dose-dependent manner and mildly inhibited the production of progesterone in mouse theca interstitial cells. Administration of GDF-9 at the dosages of 200 ng/mL and 400 ng/mL resulted in a significant decrease in the testosterone level compared with the control group by 60.42% and 68.76%, respectively. Growth differential factor-9 significantly suppressed Lhcgr mRNA by 47.36%, Cyp11a1 mRNA by 62.30%, and Cyp17a1 mRNA by 55.39%, but had only a mild effect on Star gene expression.

Conclusion(s): Growth differential factor-9 can inhibit the production of testosterone in mouse theca interstitial cells and suppress the corresponding gene expression.

Keywords: Gene expression; growth differential factor-9; hormone; theca.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Cholesterol Side-Chain Cleavage Enzyme / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Growth Differentiation Factor 9 / pharmacology*
  • Mice
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Progesterone / biosynthesis
  • RNA, Messenger / metabolism
  • Steroid 17-alpha-Hydroxylase / metabolism
  • Testosterone / metabolism*
  • Theca Cells / drug effects*
  • Theca Cells / metabolism

Substances

  • Growth Differentiation Factor 9
  • Phosphoproteins
  • RNA, Messenger
  • steroidogenic acute regulatory protein
  • Testosterone
  • Progesterone
  • Steroid 17-alpha-Hydroxylase
  • Cholesterol Side-Chain Cleavage Enzyme