The involvement of nitric oxide in corpus luteum regression in the rat: feedback mechanism between prostaglandin F-2 alpha and nitric oxide

In the corpus luteum (CL), prostaglandin F-2 alpha (PGF(2 alpha)) is a phys iological agent with luteotytic actions. Nitric oxide (NO) is a messenger m olecule capable of modulating diverse pathophysiological processes. The aim of the present study was to investigate the role of ovarian NO in PGE (a l uteotrophic prostanoid) and PGF(2 alpha) (a luteolytic prostanoid) producti on and in progesterone synthesis during CL regression in the rat. To obtain a longer functional CL, we used a pseudopregnant (PSP) rat model. By means of intrabursa ovarian sac treatment of two competitive nitric oxide syntha se (NOS) inhibitors, N-G-monomethyl-I-arginine (I-NMMA, 1 mg/kg) and N-W-ni tro-I-arginine methyl ester (I-NAME; 3 mg/kg), and sodium nitroprusside (SN P, 0.05 mg/kg) as a NO generator, we found that NO, produced by the ovarian tissue during the last 2 days of CL development (days 8 and 9), increased PGF(2 alpha) production in the ovary and diminished serum progesterone conc entrations leading to CL involution. We also proposed a positive feedback m echanism between PGF(2 alpha) and NO, to ensure luteal regression. Thus, we injected intraperitoneally a luteolytic dose (3 mu g/kg) of a synthetic PG F(2 alpha) during the mid and late phase of CL development. Ovarian NOS act ivity was evaluated. The results confirmed our hypothesis; we did not see a ny effect in the mid-stage of CL development, but increased ovarian NOS act ivity was found in PGF(2 alpha)-injected late pseudopregnant rats.