Estrogen Causes Dynamic Alterations in Endothelial Estrogen Receptor Expression
作者:
Christopher Ihionkhan,
Ken Chambliss,
Linda Gibson,
Lisa Hahner,
Michael Mendelsohn,
Philip Shaul,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 91,
issue 9
页码: 814-820
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: endothelium;estrogen;estrogen receptor &agr;;estrogen receptor &bgr;
数据来源: OVID
摘要:
Abstract—Estrogen receptor (ER)&agr; mediates many of the effects of estrogen on the vascular endothelium. The purpose of the present study was to determine whether estrogen modifies endothelial ER&agr; expression. In experiments in cultured ovine endothelial cells, physiological concentrations of 17&bgr;-estradiol (E2, 10−10to 10−8mol/L) caused an increase in ER&agr; protein abundance that was evident after 6 hours of hormone exposure. Shorter (2-hour) E2treatment caused ER&agr; downregulation. In contrast to the upregulation in ER&agr; after long-term E2, the expression of the other ER isoform, ER&bgr;, was downregulated. Both nonselective ER antagonism with ICI 182,780 and the inhibition of gene transcription with actinomycin D blocked the increase in ER&agr; with E2. In studies using the human ER&agr; gene promoter P-1 coupled to luciferase, an increase in ER&agr; gene transcription was evident in endothelial cells within 4 hours of E2exposure. The transcriptional activation was fully blocked by ICI 182,780, whereas the specific ER&bgr; antagonist RR-tetrahydrochrysene yielded partial blockade. Overexpression of ER&agr; or ER&bgr; caused comparable 10- and 8-fold increases, respectively, in ER&agr; promoter activation by E2.Thus, long-term exposure to E2upregulates ER&agr; expression in endothelial cells through the actions of either ER&agr; or ER&bgr; on ER&agr; gene transcription; in contrast, E2causes ER&bgr; downregulation in the endothelium. We postulate that E2-induced changes in ER&agr; and ER&bgr; expression modify the effects of the hormone on vascular endothelium.
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