The Effects And Mechanisms Of IL-1? On The Progesterone Production In Human Granulosa-lutein Cells

Ovulation is a complex process regulated by the temporal and spatial genes,which is initiated by the surge of luteinizing hormone.However,the mechanism underlying ovulation is not yet entirely elucidated.Although many studies on animals had confirmed that IL-1? was involved in ovulation,including oocyte maturation and regulation of ovulation-related genes expression,whether IL-1? effect on ovulation through inducing steroidogenesis in granulosa cells remains controversial.Therefore,our research aims to study the effects and mechanisms of IL-1? on the progesterone(P4)production in human granulosa-lutein cells.By using the primary cultured human granulosa-lutein cells,we found that IL-1? increased P4 production and StAR expression in a concentration-dependent manner whereas it had no effect on the protein expression of P450scc and 3?-HSD,which was attenuated by IL-1Ra Furthermore,the phosphorylation of CREB could be induced by IL-1? stimulation,and knock-down of CREB completely blocked the IL-1?-induced StAR expression and P4 production in human granulosa-lutein cells.Although IL-1? had no effect on the level of intracellular cAMP,it could activate ERK1/2,p38 and JNK MAPKs pathways Moreover,PKA inhibitor H89,adenylate cyclase inhibitor SQ22536 and JNK inhibitor SP600125 could not block the IL-1?-induced phosphorylation of CREB while ERK1/2 inhibitor PD98059 and p38 inhibitor SB203580 could block the IL-1?-induced phosphorylation of CREB as well as StAR expression and P4 production in human granulosa-lutein cells.In conclusion,IL-1? up-regulated StAR expression and increased P4 production through ERK1/2 and p38-mediated phosphorylation of CREB in human granulosa-lutein cells.These results illustrate the IL-1? effect on the P4 production in granulosa cells,and provide the molecular basis for its effect on ovulation.