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Mol Cell Endocrinol. 2014 May 25;389(1-2):65-70. doi: 10.1016/j.mce.2014.02.001. Epub 2014 Feb 11.

Endothelial estrogen receptor isoforms and cardiovascular disease.

Author information

1
Division of Cardiovascular Medicine and Departments of Internal Medicine and Immunobiology, Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA.
2
Division of Cardiovascular Medicine and Departments of Internal Medicine and Immunobiology, Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA. Electronic address: jeffrey.bender@yale.edu.

Abstract

Rapid, nongenomic vascular cell and tissue responses to estrogen have been demonstrated for more than a decade. Although the pendulum continues to swing, accumulating evidence, both clinical and pre-clinical, support favorable effects of ovarian steroid hormones in the vascular system. These effects are mediated both by classical steroid hormone receptor-mediated transcriptional modulation, and largely by endothelial plasma membrane-associated estrogen receptor (ER)α, which when engaged triggers a signaling cascade resulting in release of cardioprotective nitric oxide (NO). In addition to full-length ERα (ER66), an N-terminus truncated ERα isoform, ER46, plays a key role in these rapid endothelial responses to 17β-estradiol (E2). We have recently determined that ER46 can be a Type I integral transmembrane molecule. In this review, we discuss ER isoforms, rapid E2-stimulated signaling in the endothelium, the importance of the ER46 transmembrane orientation, and the clinical context of this rapid endothelial signaling.

KEYWORDS:

ER46; Endothelium; Estrogen; eNOS

PMID:
24530925
PMCID:
PMC4040324
DOI:
10.1016/j.mce.2014.02.001
[Indexed for MEDLINE]
Free PMC Article

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