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The Src tyrosine kinase pathway regulates thecal CYP17 expression and androstenedione secretion

Gaurav Chaturvedi1, Koji Arai, Paul F Terranova

  • 1Department of Molecular and Integrative Physiology, The Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Molecular and Cellular Biochemistry
|July 22, 2008
PubMed

Insights

Src tyrosine kinase regulates thecal cell steroidogenesis. Inhibiting Src kinase boosts androstenedione secretion and CYP17 gene expression, implicating it in ovarian androgen production.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Reproductive Science

Background:

  • Thecal cells are crucial for ovarian androgen production.
  • Src tyrosine kinase is a potential regulator of steroidogenesis.
  • Understanding Src's role can elucidate mechanisms of ovarian function.

Purpose of the Study:

  • To investigate the role of Src tyrosine kinase in mouse thecal cell steroidogenesis.
  • To determine the effect of Src inhibition on androstenedione secretion and CYP17 gene expression.

Main Methods:

  • Primary mouse theca-interstitial cells were cultured in vitro.
  • Cells were treated with PP2, a Src kinase inhibitor.
  • Androstenedione secretion, CYP17 promoter activity, and mRNA levels were measured.
  • Downstream signaling pathways, including MAPK and SF-1 phosphorylation, were assessed.

Main Results:

  • Src inhibition by PP2 significantly increased basal and forskolin-stimulated androstenedione secretion.
  • PP2 treatment elevated CYP17 promoter activity and mRNA levels.
  • Src inhibition increased mitogen-activated protein kinase phosphatase-1 and decreased SF-1 phosphorylation.
  • Inhibition of a downstream Src target, MAPK kinase, partially mimicked Src inhibition effects.

Conclusions:

  • Src tyrosine kinase plays a significant role in regulating CYP17 expression and thecal cell androgen secretion.
  • Src acts through downstream signaling pathways involving SF-1 and MAPK to modulate steroidogenesis.
  • Targeting Src kinase may offer novel therapeutic strategies for conditions involving altered ovarian androgen production.

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