Activin-A, but not inhibin, regulates 17 beta-hydroxysteroid dehydrogenasetype 1 activity and expression in cultured rat granulosa cells

17 beta -Hydroxysteroid dehydrogenase type 1 (17HSD type 1) catalyzes the r eduction of estrone (E-1) to biologically more active estradiol (E-2). In t he present study, the effect of activin, inhibin, and follistatin on 17HSD activity and 17HSD type 1 expression in cultured, unluteinized rat granulos a cells was examined. Furthermore, the effects of these hormones on 17HSD t ype 1 expression were compared with the expression of P450 aromatase (P450a rom). Rat granulosa cells were pre-incubated in serum-free media for 3 days , followed by a 2-day treatment with activin, inhibin, follistatin and 8-Br -cAMP. Activin in increasing concentrations appeared to effect a dose-depen dent increase in 17HSD activity. In addition, increasing concentrations of activin also increased 17HSD type 1 mRNA expression. Addition of 8-Br-cAMP at concentrations of 0.25 and 1.5 mmol/l together with activin significantl y augmented the stimulatory effects of activin alone in the cultured cells. Neither inhibin, nor follistatin, either alone or in combination with 8-Br -cAMP, had any notable effects on 17HSD activity and 17HSD type 1 expressio n. Preincubation of activin with increasing concentrations of Follistatin s ignificantly diminished the stimulatory effect of activin. In the presence of follistatin, activin did not significantly increase the 8-Br-cAMP-induce d 17HSD activity and 17HSD type 1 expression. The culturing of granulosa ce lls in the presence or the absence of inhibin or follistatin with or withou t 8-Br-cAMP did not alter the effect of these peptides on P450arom expressi on in rat granulosa cells as judged by Northern blot analysis of total RNA. However, cAMP-induced P450arom expression was enhanced by activin treatmen t, except when follistatin was present. This is in line with the suggested role of follistatin as an activin-binding protein, which limits the bioavai lability of activin to its membrane receptors. Thus. the results support th e notion of a paracrine/autocrine role of activin in follicular steroidogen esis of growing follicles. (C) 2000 Elsevier Science Ltd. All rights reserv ed.