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Published-Ahead-of-Print July 3, 2007, DOI:10.2164/jandrol.107.002865

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HEPATOCYTE GROWTH FACTOR MODULATES RAT LEYDIG CELL FUNCTONS

Jessica Del Bravo , Angela Catizone , Giulia Ricci , and Michela Galdieri *

* To whom correspondence should be addressed. E-mail: michela.galdieri{at}uniroma1.it.

The hepatocyte growth factor (HGF) regulates many cellular functions acting through c-met, its specific tyrosine kinase receptor. We have previously reported that in prepubertal rats HGF is secreted by the peritubular myoid cells during the entire postnatal testicular development and by the Sertoli cells only at puberty. We have also demonstrated that germ cells at different stages of development express c-met and that HGF modulates germ cell proliferation and apoptosis. In the present paper we extend our study to the interstitial compartment of the testis and we demonstrate that c-met protein is present on Leydig cells. The receptor is functionally active as demonstrated by the detected effects of HGF. We report in this paper that HGF significantly increases the amount of testosterone secreted by the Leydig cells and decreases the number of Leydig cells undergoing apoptosis. The anti-apoptotic effect of HGF is mediated by the caspase-3 activity since the active fragment of the enzyme is decreased in Leydig cells cultured in the presence of HGF. However the treatment with the growth factor does not modify the expression levels of caspase-3 mRNA. All these data indicate that HGF regulates the functional activities of the Leydig cells. Interestingly, the steroidogenetic activity of the cells is increased by HGF also culturing explants of testicular tissues as well as the anti-apoptotic effect of HGF. Therefore our data indicate that HGF has a crucial role in the regulation of male fertility.



Key words: Androgen • Fertility • Spermatogenesis • Steroidogenesis • Testis







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Copyright © 2007 by The American Society of Andrology.