This Article Full Text Full Text (PDF) All Versions of this Article: 28/6/866    most recent Author Manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Del Bravo, J. Articles by Galdieri, M. Search for Related Content PubMed PubMed Citation Articles by Del Bravo, J. Articles by Galdieri, M.

Hepatocyte Growth Factor-Modulated Rat Leydig Cell Functions

GIULIA RICCI

MICHELA GALDIERI

From the ^* Department of Histology and Medical Embryology, School of Medicine, "Sapienza" University of Rome, Rome, Italy; and Department of Experimental Medicine, Histology and Embryology Laboratory, School of Medicine, Second University of Naples and National Institute of Biostructures and Biosystems Interuniversitary Consortium—Unit of Sections of Naples, Naples, Italy.

Correspondence to: Michela Galdieri, Dip. Istologia ed Embriologia Medica, Via A. Scarpa 14, Roma 00161, Italy (e-mail: michela.galdieri{at}uniroma1.it).

Hepatocyte growth factor (HGF) regulates many cellular functions acting through c-Met, its specific tyrosine kinase receptor. We previously reported that in prepuberal 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 article, we extend our study to the interstitial compartment of the testis and demonstrate that the 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 article that HGF significantly increases the amount of testosterone secreted by the Leydig cells and decreases the number of Leydig cells undergoing apoptosis. The antiapoptotic effect of HGF is mediated by caspase-3 activity because the amount of the active fragment of the enzyme is decreased in Leydig cells cultured in the presence of HGF. However, treatment with the growth factor does not modify the expression levels of caspase-3 mRNA. These data indicate that HGF regulates the functional activities of Leydig cells. Interestingly, the steroidogenetic activity of the cells is increased by HGF in cultured explants of testicular tissues as well as the antiapoptotic effect of HGF. Therefore, our data indicate that HGF has a crucial role in the regulation of male fertility.

     Key words: c-met, HGF, testosterone, caspase-3, apoptosis, testis