REGULATION OF INDUCIBLE NITRIC-OXIDE SYNTHASE MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN PREGNANT RAT UTERUS

Nitric oxide synthases catalyze the synthesis of the biomediator, nitr ic oxide, from L-arginine in a variety of tissues. The expression and regulation of inducible isoform of nitric oxide synthase (NOS II) in t he uterus were assessed in this study by reverse transcription-polymer ase chain reaction with the use of specific primers. Results showed th e following: 1) NOS II mRNA expression in the rat uterus was substanti ally 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 comp ared 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 reduc ed by prostaglandin F-2 alpha (PGF(2 alpha); 11.6% vs. 100% in control ); 5) treatment with progesterone prevented PGF(2 alpha)-induced inhib ition in NOS II mRNA expression; 6) ICI 164384, an antiestrogen, signi ficantly increased serum progesterone concentration and stimulated NOS II expression by the uterus in a time-dependent manner; 7) as shown b y immunofluorescent studies, cells stained by NOS II antibodies were a pparent in the decidual compartment as well as in areas between myomet rial cell bundles in the pregnant rat uterus. The density of staining decreased in the specimens at labor and postpartum. We conclude that N OS 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 prostagl andins, consistent with their role in uterine activity regulation duri ng pregnancy and labor.