Regulation of inducible nitric oxide synthase messenger ribonucleic acid expression in pregnant rat uterus

Nitric oxide synthases catalyze the synthesis of the biomediator, nitric oxide, from L-arginine in a variety of tissues. The expression and regulation of inducible isoform of nitric oxide synthase (NOS II) in the uterus were assessed in this study by reverse transcription-polymerase chain reaction with the use of specific primers. Results showed the following: 1) NOS II mRNA expression in the rat uterus was substantially increased during pregnancy and decreased during labor at term; 2) RU-486 tan antagonist of progesterone) induced preterm labor and was associated with a marked decrease in NOS II mRNA expression to 60.9%, 20.3%, and 2.9% at, respectively, 6, 12, and 24 h after treatment compared with the control value (100%); 3) progesterone administration in pregnant rats significantly increased uterine NOS II gene expression (374.1% vs. 100%); 4) NOS II mRNA in the uterus was significantly reduced by prostaglandin F-2 alpha (PGF(2 alpha); 11.6% vs. 100% in control); 5) treatment with progesterone prevented PGF(2 alpha)-induced inhibition in NOS II mRNA expression; 6) ICI 164384, an antiestrogen, significantly increased serum progesterone concentration and stimulated NOS II expression by the uterus in a time-dependent manner; 7) as shown by immunofluorescent studies, cells stained by NOS II antibodies were apparent in the decidual compartment as well as in areas between myometrial cell bundles in the pregnant rat uterus. The density of staining decreased in the specimens at labor and postpartum. We conclude that NOS II gene expression in the rat uterus was enhanced during pregnancy and decreased during labor and postpartum. NOS II in rat uterus is up-regulated by progesterone and down-regulated by estrogens and prostaglandins, consistent with their role in uterine activity regulation during pregnancy and labor.