Interleukin-1beta inhibits steroidogenic bioactivity in cultured rat ovarian granulosa cells by stimulation of progesterone degradation and inhibition of estrogen formation

Interleukin (IL)-1beta is a putative regulator of ovulation and perhaps luteal function. In this work, we examine its actions on the steroidogenic cascade of the rat granulosa cell. Whereas treatment of immature granulosa cells with FSH for 72 h produced substantial increments in the accumulation of progesterone, the addition of IL- 1beta produced dose-dependent inhibition of this FSH effect. Pulse labeling of cells with [3H]pregnenolone revealed IL-1beta to effect a decrease in the FSH-supported accumulation of [3H]progesterone while enhancing the accumulation of its proximal metabolite, [3H]20(alpha)- dihydroprogesterone. IL-1beta was without effect on the activity levels of the progesterone-synthesizing enzymes, even though the corresponding transcripts were elevated. The effect of IL1beta on some progesterone- degrading enzymes was negligible (5(alpha)-reductase) or modest (3(alpha)- hydroxysteroid dehydrogenase). In contrast, IL-1beta markedly stimulated both control and FSH-supported 20(alpha)-hydroxysteroid dehydrogenase activity (4.8- and 3.3 -fold, respectively) and transcripts (16.4- and 7.5-fold, respectively). These data demonstrate an IL-1beta-mediated inhibition of gonadotropin-stimulated steroidogenesis via modulation of specific enzymes, and suggest a role for IL-1(beta) in mediating the observed decline of these bioactive hormones during ovulation and luteolysis