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This version published online on February 1, 2007
Endocrinology, doi:10.1210/en.2006-1465
A more recent version of this article appeared on May 1, 2007
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Submitted on November 3, 2006
Accepted on January 24, 2007

Testosterone Activates MAP Kinase Via Src Kinase and the EGF Receptor in Sertoli Cells

Jing Cheng, Simon C. Watkins, and William H. Walker*

Department of Cell Biology and Physiology, The University of Pittsburgh, Pittsburgh, PA 15261

* To whom correspondence should be addressed. E-mail: walkerw{at}pitt.edu.

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




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