In this report we examined the effects of growth factors and phorbol esters on steroid hydroxylase activity in cultured human thecal and granulosa-lutein cells. Treatment of thecal cells with epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-β (TGFβ), and tetradecanoyl phorbol acetate (TPA) resulted in the inhibition of forskolin- and dibutyryl cAMP-stimulated 17α-hydroxylase activity and 17α-hydroxyprogesterone and dehydroepiandrosterone production. In contrast, cAMP-stimulated 3β-hydroxysteroid dehydrogenase (3βHSD) activity was enhanced by FGF and TGFβ, and treatment with EGF enhanced cAMP-stimulated progesterone production. cAMP stimulated 3βHSD activity was unaffected by TPA (10 nmol/L) treatment, yet TPA inhibited cAMP-stimulated progesterone production. Basal 3βHSD activity and progesterone production were inhibited by TPA. In contrast to the inhibitory actions of EGF, FGF, and TGFβ on 17α- hydroxylase expression, insulin and insulin-like growth factor-I enhanced forskolin-stimulated 17α-hydroxylase activity. In granulosa-lutein cells, forskolin-stimulated aromatase activity was suppressed by EGF, FGF, and TPA. TGFβ had no effect on forskolin-stimulated aromatase activity. EGF, FGF, and TGFβ did not affect forskolin-stimulated progesterone production, whereas treatment with TPA inhibited cAMP-stimulated progesterone secretion. These data suggest that growth factors may differentially regulate cAMP dependent processes in human thecal and granulosa cells of the developing follicle.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical