Estrogen receptor subcellular localization and cardiometabolism

Altogether, available data demonstrate the prominent role of ERα nuclear effects, and, more specifically, of ERαAF-2, in the preventive effects of estrogens against obesity, diabetes, and atheroma. However, membrane ERα signaling selectively mediates some of the estrogen endothelial/vascular effects (NO release, reendothelialization) and could also contribute to the regulation of energy balance, insulin sensitivity, and glucose metabolism. Such a dissection of ERα biological functions related to its subcellular localization will help to understand the mechanism of action of “old” ER modulators and to design new ones with an optimized benefit/risk profile.