Testosterone activates mitogen-activated protein kinase via Src kinase and the epidermal growth factor receptor in sertoli cells

Endocrinology. 2007 May;148(5):2066-74. doi: 10.1210/en.2006-1465. Epub 2007 Feb 1.

Abstract

A new pathway of testosterone (T) action in Sertoli cells was recently identified that may be required to support spermatozoa production (spermatogenesis) and fertility. Specifically, T acts via the androgen receptor (AR) to rapidly activate the MAPK cascade and the cAMP response element-binding protein (CREB) transcription factor in Sertoli cells. In further characterizing the signaling pathway that transduces T actions, we now find that a population of AR is localized to the plasma membrane and that AR associates with Src kinase after T stimulation. In addition, we demonstrate that Src kinase is activated by T and that Src kinase activity is required for stimulation of the ERK MAPK and CREB. Furthermore, we determine that activation of the epidermal growth factor receptor downstream of Src contributes to the activation of the MAPK cascade and CREB. The elucidation of this nonclassical pathway of T action in the testis may provide new targets for the control of male fertility.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Androgens / pharmacology*
  • Animals
  • Cell Membrane / enzymology
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • ErbB Receptors / metabolism*
  • Male
  • Mitogen-Activated Protein Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects
  • Sertoli Cells / enzymology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Testosterone / pharmacology*
  • src-Family Kinases / metabolism*

Substances

  • Androgens
  • Cyclic AMP Response Element-Binding Protein
  • Testosterone
  • ErbB Receptors
  • src-Family Kinases
  • Mitogen-Activated Protein Kinases