Basic fibroblast growth factor promotes stem Leydig cell development and inhibits LH-stimulated androgen production by regulating microRNA expression

J Steroid Biochem Mol Biol. 2014 Oct:144 Pt B:483-91. doi: 10.1016/j.jsbmb.2014.09.016. Epub 2014 Sep 20.

Abstract

Leydig cells are the primary source of testosterone in the testes, and their steroidogenic function is strictly controlled by the hypothalamus-pituitary-gonad axis. Emerging evidence has indicated that fibroblast growth factors play a role in regulating stem Leydig cell development and steroidogenesis, but little is known about the regulatory mechanism. Using a seminiferous tubule culture system, we demonstrated that basic fibroblast growth factor (bFGF) can promote stem Leydig cell proliferation and commitment toward differentiation in testosterone-producing Leydig cells. However, these promoting effects decreased with an increase in the bFGF dose. Previous studies have reported that bFGF inhibits luteinizing hormone (LH)-stimulated androgen production by downregulating the mRNA expression of steroidogenic genes in immature Leydig cells. However, the expression levels of 677 microRNAs did not change significantly during the LH-mediated process of testosterone synthesis. Five microRNAs (miR-29a, -29c, -142-3p, -451 and -335) were identified, and their expression in immature Leydig cells was regulated simultaneously by bFGF and LH. These results suggested that the inhibition of LH-stimulated androgen production may be modulated by a change in bFGF-mediated microRNA expression, which further impacts the signaling pathway of testosterone biosynthesis and steroidogenic gene expression.

Keywords: Basic fibroblast growth factor; Development; Leydig cells; Testosterone; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Fibroblast Growth Factor 2 / pharmacology*
  • Leydig Cells / cytology
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Luteinizing Hormone / pharmacology
  • Male
  • MicroRNAs / metabolism*
  • Rats, Sprague-Dawley
  • Seminiferous Tubules / drug effects*
  • Seminiferous Tubules / metabolism
  • Testosterone / metabolism
  • Tissue Array Analysis

Substances

  • MicroRNAs
  • Fibroblast Growth Factor 2
  • Testosterone
  • Luteinizing Hormone