Estrogen Selectively Up-Regulates eNOS and nNOS in Reproductive Arteries By Transcriptional Mechanisms

Abstract

Basal eNOS and nNOS isoform expression is greatest in arteries from reproductive tissues, and isoform responses to E(2)beta are cell specific and transcriptionally regulated. Furthermore, optimal uterine vascular responses to acute E(2)beta exposure require daily E(2)beta exposure that enhances basal NOS expression and abundance.

Transcriptional regulation of endothelial nitric oxide synthase expression in uterine artery endothelial cells by c-Jun/AP-1

“…The importance of the NOS3-NO system during pregnancy has recently been reinforced by the findings that uterine artery remodeling is impaired and litter size is reduced in NOS3-null compared to wild-type mice (van der Heijden et al, 2005). In vivo, there is solid evidence showing that uterine artery endothelial NOS3 protein is increased during pregnancy Magness et al, 2001) and in the follicular phase of the estrous cycle or by estrogen replacement therapy in association with elevated circulating estrogen levels (Chen et al, 2006;Rosenfeld et al, 2003;Rupnow et al, 2001;. Available data also suggest that uterine artery endothelial NOS3 expression can be regulated at the level of transcription (Rosenfeld et al, 2003).…”

“…In vivo, there is solid evidence showing that uterine artery endothelial NOS3 protein is increased during pregnancy Magness et al, 2001) and in the follicular phase of the estrous cycle or by estrogen replacement therapy in association with elevated circulating estrogen levels (Chen et al, 2006;Rosenfeld et al, 2003;Rupnow et al, 2001;. Available data also suggest that uterine artery endothelial NOS3 expression can be regulated at the level of transcription (Rosenfeld et al, 2003). Despite significant efforts have been paid to the regulation of NOS3 expression in the uterine and placental circulations, the mechanism(s) controlling uterine and placental artery endothelial NOS3 expression currently remains unknown.…”

“…Uterine vasodilatation as shown by dramatic rises in uterine blood flow during pregnancy is required for delivering nutrients and oxygen to the developing fetus and thus is detrimental to fetal development (Lang et al, 2003). The primary NOS responsible for NO/endothelium-dependent mechanism for uterine vasodilatation is endothelial NOS3 (Byers et al, 2005;Rupnow et al, 2001), although iNOS and nNOS may play a minor role, but none of them are expressed in the uterine artery endothelium in vivo (Mershon et al, 2002;Rosenfeld et al, 2003). The importance of the NOS3-NO system has been recently further emphasized to be critical for pregnancy outcomes in the NOS3-deficient mice (van der Heijden et al, 2005).…”

“…Despite a large body of evidence accumulated showing that increased uterine artery endothelial NOS3 protein coincides with the pregnancy-associated and estrogen-induced uterine vasodilatation (Chen et al, 2006;Magness et al, 1997;Weiner et al, 1994), the mechanisms by which NOS3 expression is controlled in the UAEC are generally unknown. Uterine artery endothelial NOS3 mRNA is increased in ovariectomized sheep receiving estrogen replacement therapy (Rosenfeld et al, 2003), suggesting that uterine artery endothelial NOS3 expression might be regulated at the level of gene transcription.…”

Antenatal Betamethasone Administration Has a Dual Effect on Adult Sheep Vascular Reactivity

“…An enhanced response to KCl in arteries of the betamethasone group was also evident after known vasodilatory pathways were blocked. Nitric oxide and prostanoids affecting vasomotor activity are considered to originate predominantly from endothelium, however, in some vascular beds smooth muscle production of these bioactive molecules is known to occur (20,21). The larger response to KCl in L-NAME pretreated arteries suggests that, in sheep brachial artery, there may be contribution of the smooth muscle to NO production.…”