• Accepted Preprint first posted online on 13 September 2007

The hepatocyte growth factor system as a regulator of female and male gonadal function

  1. Mehmet Uzumcu1
  1. Department of Physiology and Biophysics, Robert Wood Johnson Medical School-UMDNJ, 675 Hoes Lane West, Piscataway, New Jersey 08854, USA 1Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, New Jersey 08901-8525, USA
  1. (Correspondence should be addressed to R Zachow; Email: zachowrj{at}umdnj.edu)

Abstract

The hepatocyte growth factor (HGF) system comprises HGF, its receptor (the c-met tyrosine kinase), HGF activator (HGFA) protein, and HGFA inhibitor (HAI). The components of the HGF system have been identified in a plethora of tissues to include the ovary and testis. In its traditional context, the HGF system works via paracrine- and autocrine-mediated feedback in which HGF (of mesenchymal origin) binds and activates c-met (within epithelial cells); target cells then respond to HGF via any number of morphogenic and functional changes. The concomitant presence of HGFA and HAI suggests that HGF bioactivity can be locally modulated. A number of studies have collectively shown that the mammalian ovary and testis contain HGF, c-met, and HGFA; very little is currently known regarding HAI within the gonad. Within the ovary, HGF controls numerous key functions which collectively regulate the growth and differentiation of ovarian follicles; these include cell growth, steroidogenesis, and apoptosis within theca cells and/or granulosa cells. Comparatively, less is known about the function of HGF within the testicular Leydig and Sertoli cells, but evidence is emerging that HGF may regulate somatic cell function, including Leydig cell steroidogenesis. Changes in the cellular origin of HGF and c-met during fetal and postnatal testicular development suggest that HGF, in collaboration with other growth factors, may regulate important aspects of testicular cell morphogenesis and differentiation which enable male sexual viability. Likewise, experimental evidence showing that HGF can modulate many vital processes which enable ovarian follicle growth, differentiation, and function indicate the importance of HGF in female reproduction. This review presents what is currently known regarding the expression of the HGF system and its function within the ovary and testis.

  • Received in final form 11 September 2007
  • Made available online as an Accepted Preprint 13 September 2007
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