Decreasing estrogen in nonpregnant women lowers uterine myometrial type I nitric oxide synthase protein expression

OBJECTIVE: Our purpose was to study the effect of estrogen on myometrial ni tric oxide synthase. STUDY DESIGN: Twenty-four women were randomly assigned to treatment with go nadotropin-releasing hormone agonist or placebo for 8 weeks before hysterec tomy, at which time samples of myometrium were collected and the serum leve ls of estrogen, nitrate, and nitrite measured. Myometrial nitric oxide synt hase was measured with the arginine-citrulline assay. The levels of endothe lial nitric oxide synthase and neuronal nitric oxide synthase were determin ed by Western blot analysis. RESULTS: Myometrial nitric oxide synthase was 88% calcium dependent but onl y partially calmodulin dependent. Women treated with gonadotropin-releasing hormone agonist had postmenopausal levels of estradiol and had significant ly lower levels of myometrial neuronal nitric oxide synthase than those in the control group. Total, endothelial, and inducible nitric oxide synthase levels in the myometrium were unchanged, as were serum nitrite and nitrate levels. CONCLUSION: Neuronal nitric oxide synthase is regulated in the myometrium b y estrogen. Myometrial nitric oxide synthase is not all calmodulin dependen t; this may represent the activity of a novel nitric oxide synthase isoform .