Basic fibroblast growth factor enhances testosterone secretion in cultured porcine Leydig cells: site(s) of action.
The effect and mechanism of action of basic fibroblast growth factor (bFGF) on testicular steroidogenesis were investigated using as a model primary cultures of purified porcine Leydig cells from immature intact animals. Basic FGF increased basal and human chorionic gonadotrophin (hCG)-induced testosterone accumulation (with an ED50 of 0.64 ng/ml bFGF, 35 pM) in the medium following a long-term treatment. The effects of bFGF (10 ng/ml, 72 h) were found at all hCG concentrations tested (0.001-1 ng/ml), the growth factor affecting the maximal steroidogenic capacity of the Leydig cells but not their sensitivity to the gonadotrophin. In this context, we have therefore investigated whether the stimulatory effect of bFGF on testosterone formation was related to an increase of the steroidogenic enzyme activities. The data obtained indicate that the growth factor did not affect the gonadotrophin action on the formation of delta 5-steroid hormone, namely dehydroepiandrosterone (DHEA) (evaluated in the presence of 10(-5) M WIN 24540, an inhibitor of 3 beta-hydroxysteroid dehydrogenase/isomerase). By contrast, bFGF (10 ng/ml, 72 h) was found to increase in a comparable manner the conversion of pregnenolone, DHEA and delta 4-androstenedione into testosterone, suggesting a stimulatory effect on 17 beta-hydroxysteroid dehydrogenase activity. Indeed, bFGF enhanced in a dose-dependent manner (ED50 = 39 pM) this enzyme activity evaluated through the conversion of delta 4-androstenedione to testosterone. These effects of bFGF on Leydig cell steroidogenic activity are probably exerted through specific membrane bFGF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Sordoillet
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C
INSERM CJF 90-08, Hôpital Sainte-Eugénie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
Savona
C
C
Chauvin
M A
MA
de Peretti
E
E
Feige
J J
JJ
Morera
A M
AM
Benahmed
M
M
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D013552:Swine; D013739:Testosterone / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D012739:Gonadal Steroid Hormones; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D013739:Testosterone; D003687:Dehydroepiandrosterone; D015067:17-Hydroxysteroid Dehydrogenases