Growth factors and phorbol-12-myristate-13-acetate modulate the follicle-stimulating hormone- and cyclic adenosine-3',5'-monophosphate-dependent regulation of 17beta-hydroxysteroid dehydrogenase type 1 expression in rat granulosa cells.

In the present study primary cultures of rat granulosa cells obtained from diethylstilbestrol (DES)-primed immature rats were used to study the regulation of 17beta-hydroxysteroid dehydrogenase (17HSD) activity and type 1 expression via protein kinase A (PKA)- and C (PKC)-dependent pathways, and by several autocrine and/or paracrine growth factors. Follicle-stimulating hormone (FSH), 8-bromo-cyclic adenosine-3',5'-monophosphate (8-Br-cAMP) and transforming growth factor beta1 (TGFbeta1) strongly enhanced 17HSD activity and type 1 expression. The stimulatory effects of FSH and 8-Br-cAMP were further potentiated by TGFbeta1. In contrast, neither phorbol-12-myristate-13-acetate (PMA), epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) nor fibroblast growth factor (bFGF) affected 17HSD activity or type 1 expression when given alone. However, they effectively neutralized the stimulatory effects of 8-Br-cAMP and FSH. The present data suggest that, in rat granulosa cells 17HSD type 1 expression is primarily induced by FSH acting via PKA-dependent pathway and the extent of the induction is modulated by PKC-dependent inhibition and autocrine/paracrine growth factors present in the ovary.