THE EFFECTS OF GROWTH-FACTORS AND PHORBOL ESTERS ON STEROID-BIOSYNTHESIS IN ISOLATED HUMAN THECA INTERNA AND GRANULOSA-LUTEIN CELLS IN LONG-TERM CULTURE

In this report we examined the effects of growth factors and phorbol e sters on steroid hydroxylase activity in cultured human thecal and gra nulosa-lutein cells. Treatment of thecal cells with epidermal growth f actor (EGF), fibroblast growth factor (FGF), transforming growth facto r-beta (TGF beta), and tetradecanoyl phorbol acetate (TPA) resulted in the inhibition of forskolin- and dibutyryl cAMP-stimulated 17 alpha-h ydroxylase activity and 17 alpha-hydroxyprogesterone and dehydroepiand rosterone production. In contrast, cAMP-stimulated 3 beta-hydroxystero id dehydrogenase (3 beta HSD) activity was enhanced by FGF and TGF bet a, and treatment with EGF enhanced cAMP-stimulated progesterone produc tion. cAMP stimulated 3 beta HSD activity was unaffected by TPA (10 nm ol/L) treatment, yet TPA inhibited cAMP-stimulated progesterone produc tion. Basal 3 beta HSD activity and progesterone production were inhib ited by TPA. In contrast to the inhibitory actions of EGF, FGF, and TG F beta on 17 alpha-hydroxylase expression, insulin and insulinlike gro wth factor-I enhanced forskolin-stimulated 17 alpha-hydroxylase activi ty. In granulosa-lutein cells, forskolin-stimulated aromatase activity was suppressed by EGF, FGF, and TPA. TGF beta had no effect on forsko lin-stimulated aromatase activity. EGF, FGF, and TGF beta did not affe ct forskolin-stimulated progesterone production, whereas treatment wit h TPA inhibited cAMP-stimulated progesterone secretion. These data sug gest that growth factors may differentially regulate cAMP-dependent pr ocesses in human thecal and granulosa cells of the developing follicle .