Estradiol-17 beta inhibits nitric oxide synthase (NOS)-II and stimulates NOS-III gene expression in the rat uterus

Nitric oxide (NO) is synthesized by NO synthases (NOS) from L-arginine in a variety of tissues, including rat uterus, Progesterone was shown to be req uired for maintaining elevated NOS II expression in pregnant rat uterus. Ho wever, effects of estrogens on uterine NOS II expression remains unclear. I n the present study, we examined whether 17 beta-estradiol regulates NO pro duction and NOS II expression in the rat uterus during pregnancy and in non pregnant rats treated with lipopolysaccharide (LPS), Rats on Day 18 of preg nancy received 17 beta-estradiol (0.5 or 5 mu g/rat). Groups of ovariectomi zed (ovx) rats received 17 beta-estradiol (5 mu g/rat) or LPS (1 mg/rat) or a combination of the two or received vehicle only, All rats were sacrifice d 24 h after treatments. Nitrite concentrations in uterine cultures were me asured by Greiss reaction, Uterine NOS II and NOS III proteins and mRNA lev els were determined by Western blotting and reverse transcription polymeras e chain reaction, respectively. In the pregnant rat, estradiol administrati on caused inhibition in total NO production, suppression of both mRNA and p rotein levels of NOS II enzyme, and increase in NOS III mRNA and protein le vels in the uterus in a dose-dependent manner. The data indicate that estra diol inhibits NOS II and total NO generation and stimulates NOS III express ion. In ovx rats, LPS stimulated NOS II mRNA and NO production by the uteru s, Coadministration of 5 mu g estradiol profoundly suppressed NOS II mRNA a nd NO generation but elevated NOS III mRNA, Thus, estradiol inhibited LPS-i nduced increases in NOS II mRNA, Estradiol inhibits NO production by NOS II through the inhibition of NOS II expression in the rat uterus, This inhibi tion of NOS II expression occurs whether NOS II expression is constitutive (pregnancy) or induced (LPS-treated nonpregnant). Estradiol inhibition of N OS II expression occurs in the presence (pregnancy) or absence (ovx) of pro gesterone. Estradiol may play a role in regulating NOS II expression and NO production and uterine contractility during pregnancy and labor.