Document Detail

Transforming growth factor beta 1 inhibits gonadotropin action in cultured porcine Sertoli cells.
MedLine Citation:
PMID:  1370796     Owner:  NLM     Status:  MEDLINE    
In the present study, we have tested the effects of transforming growth factor beta 1 (TGF beta 1) on FSH action toward aromatase activity and lactate production in cultured Sertoli cells isolated from immature porcine testes. Whereas treatment of Sertoli cells with FSH resulted in a dose-dependent increase (about 7-fold) in aromatase activity (conversion of testosterone into estradiol) (ED50 = 80 ng/ml FSH), the addition of TGF beta 1 reduced this gonadotropin action. The inhibitory effect of TGF beta 1 on FSH aromatase activity was dose dependent (ED50 = 0.1 ng/ml, 4 pM TGF beta 1) with a maximal decrease (about 40%) observed after a long term (48-h) treatment. TGF beta 1 exerted its inhibitory effect on FSH action at the level(s) of cAMP accumulation, exerting no apparent effect on the gonadotropin receptor or at a site(s) related to cAMP action. TGF beta 1 (2 ng/ml) significantly (P less than 0.002) reduced (52% decrease) FSH-stimulated cAMP levels in cultured porcine Sertoli cells. However, such an inhibitory effect of the growth factor was no longer observed when stimulation of cAMP accumulation with FSH occurred in the presence of methyl isobutyl xanthine (0.5 mM), an inhibitor of cAMP-phosphodiesterase activity. This observation suggests that TGF beta 1 decreased cAMP levels by increasing catabolism of the cyclic nucleotide through an enhancement of cAMP-phosphodiesterase activity. The inhibitory effect of TGF beta 1 was not limited to the action of FSH on aromatase activity but also extended to the gonadotropin action (mediated by cAMP) on lactate production. As for the inhibitory effect of TGF beta 1 on FSH-induced aromatase activity, the inhibitory effect of the growth factor on FSH-stimulated lactate production was dose and time dependent with a maximal decrease (about 30%) observed in the picomolar range (1 ng/ml, 40 pM) after 48 h treatment with TGF beta 1. In conclusion, the present study demonstrates that TGF beta 1 attenuates FSH action on Sertoli cell activity and that such inhibitory action is potentially exerted through a decrease in cAMP levels. Because of the local production of TGF beta 1, it is suggested that the effects of the growth factor reported here might be exerted in the context of the testicular paracrine mechanisms.
A M Morera; G Esposito; C Ghiglieri; M A Chauvin; D J Hartmann; M Benahmed
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  130     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1992 Feb 
Date Detail:
Created Date:  1992-03-03     Completed Date:  1992-03-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  831-6     Citation Subset:  AIM; IM    
INSERM CJF 90-08, Laboratoire de Biochimie, Hôpital Sainte Eugénie, Pierre-Bénite, France.
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MeSH Terms
1-Methyl-3-isobutylxanthine / pharmacology
3',5'-Cyclic-AMP Phosphodiesterases / metabolism
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Aromatase / metabolism*
Cells, Cultured
Cyclic AMP / metabolism*
Dose-Response Relationship, Drug
Drug Interactions
Follicle Stimulating Hormone / antagonists & inhibitors,  pharmacology*
Lactates / metabolism
Receptors, FSH / drug effects,  metabolism
Sertoli Cells / drug effects,  metabolism*
Transforming Growth Factor beta / pharmacology*
Reg. No./Substance:
0/Lactates; 0/Receptors, FSH; 0/Transforming Growth Factor beta; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 28822-58-4/1-Methyl-3-isobutylxanthine; 60-92-4/Cyclic AMP; 9002-68-0/Follicle Stimulating Hormone; EC; EC',5'-Cyclic-AMP Phosphodiesterases

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