Abstract:
:TGF beta1 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 beta1 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 beta1 in organ culture after day 13.5 might be related to an elevated intratesticular concentration that would already exert maximal biological effect. On the contrary, in a model of dispersed testicular cells in culture, TGF beta1 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 48 h of treatment with 1 ng/ml TGF beta1, 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 beta1 is located after the production of cAMP. However, TGF beta1 was also able to inhibit LH-induced cAMP production. As demonstrated by the transformation of steroidogenic precursors into testosterone, TGF beta1 did not significantly alter 3beta-hydroxysteroid dehydrogenase (3beta HSD) activity but induced a strong inhibition of cytochrome P450 17alpha-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 beta1 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 3beta HSD positive cells. Taken together these results suggest that TGF beta1 likely plays a morphogenic and physiological role very early in the fetal testis via paracrine/autocrine mechanisms.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Gautier C,Levacher C,Saez JM,Habert Rdoi
10.1016/s0303-7207(97)00087-7subject
Has Abstractpub_date
1997-07-04 00:00:00pages
21-30issue
1eissn
0303-7207issn
1872-8057pii
S0303720797000877journal_volume
131pub_type
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