Transforming growth factor beta 1 inhibits steroidogenesis in dispersed fetal testicular cells in culture

[摘要] TGF beta 1 has been detected by immunohistochemistry in the rat Fetal testis. Therefore, we attempted to determine whether this factor can act as a local regulator of Leydig cell function during fetal development. An inhibitory effect of TGF beta 1 on basal and luteinizing hormone (LH)-stimulated testosterone secretion by fetal testes in vitro was observed only with testes from 13.5 day-old fetuses and not with testes from older stages. The lack of effect of exogenous TGF beta 1 in organ culture after day 13.5 might be related to an elevated intratesticular concentration that would already exerr maximal biological effect. On the contrary, in a model of dispersed testicular cells in culture, TGF beta 1 was able to inhibit LH-stimulated testosterone production by fetal Leydig cells from 16.5 and 20.5 day-old fetuses. This inhibition of LH-stimulated testosterone production was dose- and time-dependent and was maximal after 45 h of treatment with 1 ng/ml TGF beta 1, with testosterone secretion being reduced to 25% of control values. Inhibition of testosterone secretion was also observed in basal and dbcAMP-stimulated conditions, suggesting that one site of action of TGF beta 1 is located after the production of cAMP. However, TGF beta 1 was also able to inhibit LH-induced cAMP production. As demonstrated by the transformation of steroidogenic precursors into testosterone, TGF beta 1 did not significantly lter 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity but induced a strong inhibition of cytochrome P450 17 alpha-hydroxylase/C17-20 lyase (P450C17) activity which was associated with a marked diminution of cytochrome P450C17 mRNA levels (26% of control values) but not of cytochrome P450scc mRNA. In addition to its effect on steroidogenesis, TGF beta 1 exhibited morphogenic actions on the fetal testicular cells, inducing spreading when the cells were adherent and aggregation when the cells were cultured in conditions of lesser adherence and without any significant effect on either total cell number or 3 beta HSD positive cells. Taken together these results suggest that TGF beta 1 likely plays a morphogenic and physiological role very early in the fetal testis via paracrine/autocrine mechanisms. (C) 1997 Elsevier Science Ireland Ltd.

[发布日期] 1997-07-04

[关键词] fetal testis;Leydig cell;transforming growth factor beta 1;steroidogenesis