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 nitric oxide synthase.


METHODS
Twenty-four women were randomly assigned to treatment with gonadotropin-releasing hormone agonist or placebo for 8 weeks before hysterectomy, at which time samples of myometrium were collected and the serum levels of estrogen, nitrate, and nitrite measured. Myometrial nitric oxide synthase was measured with the arginine-citrulline assay. The levels of endothelial nitric oxide synthase and neuronal nitric oxide synthase were determined by Western blot analysis.


RESULTS
Myometrial nitric oxide synthase was 88% calcium dependent but only partially calmodulin dependent. Women treated with gonadotropin-releasing hormone agonist had postmenopausal levels of estradiol and had significantly 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.


CONCLUSIONS
Neuronal nitric oxide synthase is regulated in the myometrium by estrogen. Myometrial nitric oxide synthase is not all calmodulin dependent; this may represent the activity of a novel nitric oxide synthase isoform.
Weeks
A D
AD
Department of Obstetrics and Gynaecology, Research School of Medicine, Leeds, United Kingdom.
Massmann
A G
AG
Monaghan
J M
JM
Crowther
D
D
Duffy
S R
SR
Walker
J J
JJ
Figueroa
J P
JP
D000328:Adult; D015153:Blotting, Western; D020013:Calcium Signaling; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D016729:Leuprolide / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects* / Q000201:enzymology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000097:blood
D009566:Nitrates; D009573:Nitrites; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D016729:Leuprolide