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

The presence of both estrogen receptor α (ERα) and ERβ 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 ERα or ERβ. The activities of ERα and ERβ were compared in three distinct gene regulatory pathways, including inhibition of IL-1β induction of E-selectin expression, inhibition of basal endothelin-1 production, and the ability to induce two matrix-stabilizing enzymes: tissue transglutaminase and a novel member of the lysyl oxidase family. Both ERs were active on these end points, although ERβ was typically less efficacious than ERα. As no class of gene regulation could differentiate ERα from ERβ activity, we characterized a novel steroid (7α-thiophenyl-E2) that bound with similar affinities to ERα and ERβ, but functioned as an ERα agonist and ERβ antagonist for all of these endothelial responses. This pattern of receptor sub...