Interleukin-1beta up-regulates nitrite production: effects on ovarian function.
We have previously reported that Interleukin-1beta (IL-1beta) affects ovarian function in the rat, modulating prostaglandin and progesterone (P) production. As IL-1beta effects were associated to nitric oxide (NO) synthesis, in the present work we have further examined the role of ovarian NOS-system, in IL-1beta antisteroidogenic action. Mid-luteal explants from rats were incubated for 4 h in the presence of IL-1beta (1-35 ng/ml)-alone or in combination with NOS-inhibitors-and then assayed for P and nitrite production. IL-1beta treatment reduced P levels in a dose-dependent manner, returning to basal levels at 35 ng/ml. This reduction in steroid synthesis was paralleled by a dose-dependent increase in nitrite levels, reaching a maximum at 25 ng/ml but without effect at 35 ng/ml. L-Arginine (1 and 2 mM) was able to mimic IL-1beta actions and the NOS blocker L-Nitro-Arginin-Methyl Ester reverted these effects. Moreover, the selective iNOS inhibitor, 1400 W, completely abolished IL-1beta antisteroidogenic effect, therefore confirming the dependence of IL-1beta action upon iNOS activation. Finally, IL-1beta did not affect eNOS expression but up-regulated iNOS mRNA and protein levels. Our results suggest an interaction between IL-1beta and the NOS-system. Thus, we may conclude that in the rat iNOS-derived NO production, induced by IL-1beta, affects ovarian P biosynthesis and hence NO may be a major effector molecule of ovarian IL-1 system.
Estévez
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A
Center for Pharmacological and Botanical Studies (CEFYBO)-Council of Scientific and Technical Investigation (CONICET), Serrano 669 CP (1414), Buenos Aires, Argentina. alestevez@yahoo.com
Farina
M
M
Franchi
A
A
Johnson
C
C
Vega
M
M
Motta
A B
AB
D000818:Animals; D005260:Female; D007375:Interleukin-1 / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction; D015854:Up-Regulation
D007375:Interleukin-1; D009573:Nitrites; D009569:Nitric Oxide; D011374:Progesterone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat