Estrogen Receptors α and β Have Similar Activities in Multiple Endothelial Cell Pathways

Mark J. Evans, Heather A. Harris, Chris P. Miller, Sotirios K. Karathanasis, Steven J. Adelman
2002 Endocrinology  
The presence of both estrogen receptor ␣ (ER␣) and ER␤ in vascular cells has greatly increased the complexity of potential estrogen regulatory pathways in the cardiovascular system. Here, human umbilical vein endothelial cells were engineered using adenovirus vectors to express either ER␣ or ER␤. The activities of ER␣ and ER␤ were compared in three distinct gene regulatory pathways, including inhibition of IL-1␤ induction of E-selectin expression, inhibition of basal endothelin-1 production,
more » ... in-1 production, and the ability to induce two matrixstabilizing enzymes: tissue transglutaminase and a novel member of the lysyl oxidase family. Both ERs were active on these end points, although ER␤ was typically less efficacious than ER␣. As no class of gene regulation could differentiate ER␣ from ER␤ activity, we characterized a novel steroid (7␣thiophenyl-E2) that bound with similar affinities to ER␣ and ER␤, but functioned as an ER␣ agonist and ER␤ antagonist for all of these endothelial responses. This pattern of receptor subtype-selective activity was not unique to endothelial cells, but was also seen in metabolically active HepG2 cells, suggesting potential in vivo utility. The panel of endothelial responses coupled with a selective modulator should provide a means to characterize the roles of ER␣ and ER␤ in endothelial cells in vivo.
doi:10.1210/en.2002-220356 pmid:12239089 fatcat:f3r7kogurrertl6atztyfws73y