Estrogen causes dynamic alterations in endothelial estrogen receptor expression

Christopher E. Ihionkhan, Ken L. Chambliss, Linda L. Gibson, Lisa D. Hahner, Michael E. Mendelsohn, Philip W. Shaul

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Estrogen receptor (ER)α mediates many of the effects of estrogen on the vascular endothelium. The purpose of the present study was to determine whether estrogen modifies endothelial ERα expression. In experiments in cultured ovine endothelial cells, physiological concentrations of 17β-estradiol (E2, 10-10 to 10-8 mol/L) caused an increase in ERα protein abundance that was evident after 6 hours of hormone exposure. Shorter (2-hour) E2 treatment caused ERα downregulation. In contrast to the upregulation in ERα after long-term E2, the expression of the other ER isoform, ERβ, was downregulated. Both nonselective ER antagonism with ICI 182,780 and the inhibition of gene transcription with actinomycin D blocked the increase in ERα with E2. In studies using the human ERα gene promoter P-1 coupled to luciferase, an increase in ERα gene transcription was evident in endothelial cells within 4 hours of E2 exposure. The transcriptional activation was fully blocked by ICI 182,780, whereas the specific ERβ antagonist RR-tetrahydrochrysene yielded partial blockade. Overexpression of ERα or ERβ caused comparable 10- and 8-fold increases, respectively, in ERα promoter activation by E2. Thus, long-term exposure to E2 upregulates ERα expression in endothelial cells through the actions of either ERα or ERβ on ERα gene transcription; in contrast, E2 causes ERβ downregulation in the endothelium. We postulate that E2-induced changes in ERα and ERβ expression modify the effects of the hormone on vascular endothelium.

Original languageEnglish (US)
Pages (from-to)814-820
Number of pages7
JournalCirculation research
Volume91
Issue number9
DOIs
StatePublished - Nov 1 2002

Keywords

  • Endothelium
  • Estrogen
  • Estrogen receptor α
  • Estrogen receptor β

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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