Direct regulating effects of transforming growth factor beta on the Leydig cell steroidogenesis in primary culture.
The effect of transforming growth factor beta on testicular steroidogenesis was studied by using a model of immature porcine Leydig cells cultured in a chemically defined medium. Leydig cells were cultured in the presence of human or porcine purified TGF beta and the following parameters were measured: cell proliferation, LH/hCG binding, and hCG-stimulated steroid hormone productions (DHEA, DHEAS and testosterone). Whereas TGF beta from the two sources had no effect on Leydig cell multiplication, it markedly inhibited LH/hCG-stimulated DHEA and DHEAS in a time- and dose-dependent manner. The maximal inhibitory effect of this peptide on LH/hCG binding (65% decrease), hCG-stimulated DHEA (77% decrease) and DHEAS (92% decrease) productions was observed with 2 ng/ml for 48 h of treatment. In contrast, TGF beta exerted a biphasic effect on hCG-stimulated testosterone production: stimulating (110% increase) until 2 ng/ml and inhibiting (35% decrease) for higher concentrations. [125I]TGF beta was cross-linked to Leydig cells using disuccinimidyl suberate; cells affinity labelled with [125I]TGF beta exhibit a major labelled band of approx 280 kDa, which has the properties expected from a TGF beta receptor. These data demonstrate that TGF beta is a direct potent regulator of Leydig cell steroidogenic function and its effects are probably mediated via a specific receptor.
Morera
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AM
Groupe de recherche sur les interactions cellulaires, Hopital Sainte-Eugénie, Pierre-Bénite, France.
Cochet
C
C
Keramidas
M
M
Chauvin
M A
MA
de Peretti
E
E
Benahmed
M
M
D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011974:Receptors, LH / Q000378:metabolism; D013552:Swine; D015291:Transforming Growth Factors
D000728:Androgens; D006063:Chorionic Gonadotropin; D006133:Growth Substances; D010455:Peptides; D011974:Receptors, LH; D015291:Transforming Growth Factors