INTERLEUKIN-1-BETA INHIBITS STEROIDOGENIC BIOACTIVITY IN CULTURED RATOVARIAN GRANULOSA-CELLS BY STIMULATION OF PROGESTERONE DEGRADATION AND INHIBITION OF ESTROGEN FORMATION

Interleukin (IL)-1 beta is a putative regulator of ovulation and perha ps luteal function. In this work, we examine its actions on the steroi dogenic cascade of the rat granulosa cell. Whereas treatment of immatu re granulosa cells with FSH for 72 h produced substantial increments i n the accumulation of progesterone, the addition of IL-1 beta produced dose-dependent inhibition of this FSH effect. Pulse labeling of cells with [H-3]pregnenolone revealed IL-1 beta to effect a decrease in the FSH-supported accumulation of [H-3]progesterone while enhancing the a ccumulation of its proximal metabolite, [H-3]20 alpha-dihydroprogester one. IL-1 beta was without effect on the activity levels of the proges terone-synthesizing enzymes, even though the corresponding transcripts were elevated. The effect of IL-1 beta on some progesterone-degrading enzymes was negligible (5 alpha-reductase) or modest (3 alpha-hydroxy steroid dehydrogenase). In contrast, IL-1 beta markedly stimulated bot h control and FSH-supported 20 alpha-hydroxysteroid dehydrogenase acti vity (4.8- and 3.3-fold, respectively) and transcripts (16.4- and 7.5- fold, respectively). These data demonstrate an IL-1 beta-mediated inhi bition of gonadotropin-stimulated steroidogenesis via modulation of sp ecific enzymes, and suggest a role for IL-1 beta in mediating the obse rved decline of these bioactive hormones during ovulation and luteolys is.