On the mechanisms involved in the inhibitory and stimulating actions of transforming growth factor-β on porcine testicular steroidogenesis: an in vitro study

Abstract By using immature porcine Leydig cells cultured in defined medium as a model, transforming growth factor-β (TGFβ) was shown to exert a dramatic inhibitory effect on their basal and human chorionic gonadotropin (hCG) (or 8-bromo-cyclic AMP) stimulated dehydroepiandrosterone secretion, in the presence or absence of saturating concentrations of exogenous (low density lipoprotein) cholesterol substrate. In contrast, TGFβ exerted both a stimulating and inhibitory effect on testosterone secretion: while hCG-stimulated testosterone secretion was enhanced by low doses of TGFβ (0.06–0.4 ng/ml, 48 h), it was decreased with higher concentrations of TGFβ (2.5–10 ng/ml 48 h). The data obtained show that the inhibitory action of TGFβ on testicular steroidogenesis was related to a decrease in pregnenolone formation by affecting a step(s) distal to cyclic AMP formation but before cholesterol association with cytochrome P-450 side-chain cleavage. As for the stimulatory effect of TGFβ on testosterone formation, this was mainly related to an increase (about 2-fold) in 3β-hydroxysteroid dehydrogenase/isomerase activity (ED 50 0.05 ng/ml, 2 × 10 −13 M ). The results indicate that the (short-term) steroidogenic stimulatory action of luteinizing hormone (LH)/hCG is antagonized by high concentrations of TGFβ by decreasing pregnenolone formation while it is enhanced by the stimulating action of low concentrations of TGFβ exerted on 3β-hydroxy steroid dehydrogenase/isomerase activity.