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 (an 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 F2alpha (
PGF2alpha; 11.6% vs. 100% in control); 5) treatment with
progesterone prevented
PGF2alpha-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.