Estrogen Receptor-β Mediates Estradiol-Induced Pregnancy-Specific Uterine Artery Endothelial Cell Angiotensin Type-2 Receptor Expression

Hypertension
Jay S MishraSathish Kumar

Abstract

The pregnancy-augmented uterine vasodilation is linked to increased AT2R (angiotensin type-2 receptor) that mediates the vasodilatory effects of angiotensin II. However, the mechanisms controlling AT2R expression during pregnancy remain unclear. Estrogens are known to play a role in vascular adaptations during pregnancy. We hypothesized that estrogen stimulates uterine artery AT2R expression via ER (estrogen receptor)-β-dependent transcription in a pregnancy-specific endothelium-dependent manner. Plasma estradiol levels increased and peaked in late pregnancy and returned to prepregnant levels post-partum, correlating with uterine artery AT2R and ERβ upregulation. Estradiol stimulated AT2R mRNA expression in endothelium-intact but not endothelium-denuded late pregnant and nonpregnant rat uterine artery ex vivo. Consistently, estradiol stimulated AT2R mRNA expression in late pregnant but not nonpregnant primary human uterine artery endothelial cells in vitro, which was abolished by ER antagonist ICI 182,780. Higher ERα protein bound to ER-responsive elements in AT 2 R promoter in the nonpregnant arteries whereas higher ERβ bound in the pregnant state. ERα protein levels were similar but higher ERβ protein levels were expressed in...Continue Reading

References

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Citations

Jun 24, 2020·International Journal of Molecular Sciences·Jin BaiDong-Bao Chen
Mar 22, 2020·International Journal of Molecular Sciences·Kathirvel Gopalakrishnan, Sathish Kumar
Apr 12, 2020·International Journal of Molecular Sciences·Maurizio Mandalà
Dec 20, 2020·Molecular and Cellular Endocrinology·Rosalieke E WiegelA H Jan Danser
Apr 21, 2021·Molecular and Cellular Endocrinology·Rosalieke E WiegelA H Jan Danser
Jul 6, 2021·Frontiers in Cardiovascular Medicine·Lin ZhangHong Sun
Aug 28, 2021·International Journal of Molecular Sciences·Xiangqun Hu, Lubo Zhang

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