On the mechanisms involved in the inhibitory and stimulating actions of transforming growth factor-beta on porcine testicular steroidogenesis: an in vitro study.
By using immature porcine Leydig cells cultured in defined medium as a model, transforming growth factor-beta (TGF beta) 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, TGF beta exerted both a stimulating and inhibitory effect on testosterone secretion: while hCG-stimulated testosterone secretion was enhanced by low doses of TGF beta (0.06-0.4 ng/ml, 48 h), it was decreased with higher concentrations of TGF beta (2.5-10 ng/ml, 48 h). The data obtained show that the inhibitory action of TGF beta 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 TGF beta on testosterone formation, this was mainly related to an increase (about 2-fold) in 3 beta-hydroxysteroid dehydrogenase/isomerase activity (ED50 0.05 ng/ml, 2 X 10(-13) M). The results indicate that the (short-term) steroidogenic stimulatory action of luteinizing hormone (LH)/hCG is antagonized by high concentrations of TGF beta by decreasing pregnenolone formation while it is enhanced by the stimulating action of low concentrations of TGF beta exerted on 3 beta-hydroxy steroid dehydrogenase/isomerase activity.
Benahmed
M
M
Laboratoire de Biochimie, Hôpital Sainte Eugénie, Centre Hospitalier Lyon-Sud, France.
Sordoillet
C
C
Chauvin
M A
MA
de Peretti
E
E
Morera
A M
AM
D000728:Androgens / Q000096:biosynthesis*; D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D066298:In Vitro Techniques; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008858:Microscopy, Phase-Contrast; D011284:Pregnenolone / Q000096:biosynthesis; D013552:Swine; D013739:Testosterone / Q000096:biosynthesis; D015291:Transforming Growth Factors / Q000502:physiology*
D000728:Androgens; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D011284:Pregnenolone; D015291:Transforming Growth Factors