Molecular Human Reproduction, Vol. 10, No. 2, pp. 115-122, 2004
© European Society of Human Reproduction and Embryology 2004
Augmented endothelial nitric oxide synthase (eNOS) protein expression in human pregnant myometrium: possible involvement of eNOS promoter activation by estrogen via both estrogen receptor (ER)
and ERß
1Department of Gynecology and Obstetrics and 2Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
3 To whom correspondence should be addressed. e-mail: fetus{at}kuhp.kyoto-u.ac.jp
The aim of the present study was to investigate the possible contribution of estrogen to pregnancy-associated modulation of nitric oxide production in the human myometrium during pregnancy. Both endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) proteins were clearly expressed in the non-pregnant myometrium and were elevated in the first trimester of pregnancy. Oral contraceptive pills augmented eNOS, but not iNOS, protein expression in the non-pregnant human myometrium. In cultured human myometrial cells, estrogen receptor (ER)
and ERß expression was extremely low. Therefore, we used either ER or ERß expression vector to investigate the effect of 17ß-estradiol treatment on eNOS promoter activity using eNOS promoter/luciferase vector in cultured human myometrial cells. 17ß-estradiol treatment significantly augmented eNOS promoter activity in cells co-transfected with either ER or ERß, and this augmentation was dose-dependently suppressed by ICI 182780, an estrogen antagonist. These data suggest the possibility that both ER and ERß are involved in the estrogen-associated regulation of eNOS gene expression in the human myometrium.
Key words: Key words: endothelial nitric oxide synthase/estrogen/estrogen receptor/myometrium/pregnancy
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