Interleukin-1beta in the functional and structural luteolysis. Relationship with the nitric oxide system.
The aim of the present report was to investigate the in vitro effect of interleukin-1beta(IL-1beta) on corpus luteum (CL) function and some aspects of this mechanism involved. Ovarian rat dispersates from mid-luteal phase were exposed to different doses of IL-1beta (1, 10, 20 ng/ml). Meanwhile 1, 10 and 20 ng/ml of IL-1beta decreased progesterone (P4) production, only the highest doses of IL-1beta increased prostaglandin F2alpha (PGF2alpha) levels. To investigate the possible relationship between PGs production and P4 synthesis, we incubated together IL-1beta (20 ng/ml) and indomethacin (0.1 mM) a potent inhibitor of cyclooxygenase pathway. We found that P4 inhibition induced by IL-1beta was completely prevented by addition of indomethacin. On the other hand, when ovarian rat tissue were exposed at 20 ng/ml of IL-1beta (doses that affected both PGF2alpha and P4 production) the nitric oxide synthase (NOS) activity was augmented. Moreover, IL-1beta effects on PGF2alpha and P4 levels were impaired when a NOS inhibitor N(W)-nitro- L -arginine methyl ester (L-NAME, 600 microM) was added to the incubation media. These data demonstrate that: (i) at the tested doses (1-20 ng/ml), IL-1beta is involved in CL function through the diminution of P4 production of whole ovarian dispersate culture; (ii) at the highest doses assayed (20 ng/ml) IL-1beta increased PGF2alpha production; (iii) at these doses, IL-1beta decreased P4 production by means of a cyclooxygenase pathway and (iv) the NO system would be a key intermediary second messenger in the IL-1beta actions.
Estevez
A
A
Centro de Estudios Farmacológicos y Botánicos--Consejo de Investigaciones Científicas y Técnicas, Serrano, Buenos Aires, Argentina. alestevez@yahoo.com
Tognetti
T
T
Rearte
B
B
Sander
V
V
Motta
A B
AB
D000818:Animals; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost / Q000096:biosynthesis; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D003341:Luteolysis / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000096:biosynthesis / Q000097:blood; D011555:Pseudopregnancy; D051381:Rats
D007375:Interleukin-1; D009569:Nitric Oxide; D011374:Progesterone; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester