EFFECTS OF ACIDIC FIBROBLAST GROWTH-FACTOR ON 5-ENE-3 BETA-HYDROXYSTEROID DEHYDROGENASE-ISOMERASE AND 5-ALPHA-REDUCTASE ACTIVITIES AND [I-125] HUMAN CHORIONIC-GONADOTROPIN BINDING IN CULTURED IMMATURE LEYDIG-CELLS

The present studies examined the effects of acidic fibroblast growth factor (aFGF) on 5-ene-3beta-hydroxysteroid dehydrogenase-isomerase (3beta-HSD) and 5alpha-reductase activities and [I-125]human chorionic gonadotrophin ([I-125]hCG) binding in cultured immature rat Leydig cells. Increasing concentrations of aFGF (0.1-20 ng/ml) progressively decreased basal 3beta-HSD activity from 0.474+/-0.0335 to 0.093+/-0.0004 nmol progesterone/30 min/10(5) cells. This inhibition by aFGF (10 ng/ml) was partially reversed by 1 mug/ml insulin or 100 ng/ml insulin-like growth factor-I. Increasing aFGF concentrations (0.1-10 ng/ml) also inhibited hCG-stimulated 5alpha-reductase activity in a dose-dependent manner, but had only a modest effect on basal enzyme activity. Increasing aFGF (0.1-200 ng/ml) also progressively inhibited [I-125]hCG binding in cultured immature Leydig cells. These studies demonstrate a similarity in the inhibitive effects of aFGF with bFGF effects on 3beta-HSD and 5alpha-reductase activities and [I-125]hCG binding to LH receptors, although, generally, higher aFGF concentrations were required to elicit maximal inhibitive effects. However, aFGF differed from the actions of bFGF on 3beta-HSD activity and LH receptor levels in that a secondary increase with higher growth factor concentrations was not observed.