Abstract

We have previously reported that Interleukin-1? (IL-1?) affects ovarian function in the rat, modulating prostaglandin and progesterone (P) production. As IL-1? effects were associated to nitric oxide (NO) synthesis, in the present work we have further examined the role of ovarian NOS-system, in IL-1? antisteroidogenic action. Mid-luteal explants from rats were incubated for 4h in the presence of IL-1? (1-35ng/ml) - alone or in combination with NOS-inhibitors - and then assayed for P and nitrite production. IL-1? treatment reduced P levels in a dose-dependent manner, returning to basal levels at 35ng/ml. This reduction in steroid synthesis was paralleled by a dose-dependent increase in nitrite levels, reaching a maximum at 25ng/ml but without effect at 35ng/ml. L-Arginine (1 and 2mM) was able to mimic IL-1? actions and the NOS blocker L-Nitro-Arginin-Methyl Ester reverted these effects. Moreover, the selective iNOS inhibitor, 1400W, completely abolished IL-1? antisteroidogenic effect, therefore confirming the dependence of IL-1? action upon iNOS activation. Finally, IL-1? did not affect eNOS expression but up-regulated iNOS mRNA and protein levels. Our results suggest an interaction between IL-1? and the NOS-system. Thus, we may conclude that in the rat iNOS-derived NO production, induced by IL-1?, affects ovarian P biosynthesis and hence NO may be a major effector molecule of ovarian IL-1 system. © 2004 Elsevier Inc. All rights reserved.