Estrogen Does Not Induce the Calcium-Dependent Nitric Oxide Synthase in Cultured Human Uterine Endothelial and Myometrial Smooth Muscle Cells

Abstract

In many tissues, estrogen-induced vasodilatation is mediated, at least in part, by the release of nitric oxide (NO). We determined whether human myometrial endothelial and smooth muscle cells express estrogen receptors (ERs) and whether endothelial NO synthase (eNOS) expression in these cells was affected by 17β-estradiol (10^–13–10^–6M). ER was strongly expressed in myometrial smooth muscle cells but was absent from endothelial cells. Expression of eNOS mRNA was strong in endothelial cells, but weak in muscle cells. 17β-estradiol administration for 24 or 72 h failed to increase eNOS in both cell types. Thus, an increase of human uterine blood flow by estrogens appears not to be mediated by stimulation of myometrial eNOS expression.

Expression of endothelial nitric oxide synthase in the uterus of patients with leiomyoma or adenomyosis

“…25 In regard to the effect of estrogen on eNOS, many investigators have reported that estrogen up-regulates eNOS expression. By contrast, Zervou et al 12 and Tschugguel et al 26 could not demonstrate up-regulation of eNOS expression by estrogen. Activation of eNOS is induced by cytokines, such as transforming growth factor-b, 27 and expression of eNOS is inhibited by tumor necrosis factor-a.…”

“…By contrast, Zervou et al 12 . and Tschugguel et al 26 . could not demonstrate up‐regulation of eNOS expression by estrogen.…”

Testosterone dependent androgen receptor stabilization and activation of cell proliferation in primary human myometrial microvascular endothelial cells

“…HMMECs were isolated as described previously (21) with some modifications (see Supplemental Materials and Methods). The experiments were conducted on passage-four HMMECs, which were cultured as described in Supplemental Materials and Methods.…”

Gender differences in coronary artery diameter reflect changes in both endothelial Ca2+and ecNOS activity

“…Estrogen has been shown to increase the level of ecNOS mRNA in cultured pulmonary artery endothelial cells (36) and in uterine arteries (56). However, estrogen was not shown to increase ecNOS mRNA in cultured human myometrial or bovine aortic endothelial cells (52). A recent study by Kleinert et al (29) provides direct evidence for a 1.8-fold increase in ecNOS protein expression by physiological levels of estrogen in cultured human endothelial cells.…”