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Journal Article
Research Support, N.I.H., Extramural
Unliganded estrogen receptor alpha regulates vascular cell function and gene expression.
Molecular and Cellular Endocrinology 2017 Februrary 16
The unliganded form of the estrogen receptor is generally thought to be inactive. Our prior studies, however, suggested that unliganded estrogen receptor alpha (ERα) exacerbates adverse vascular injury responses in mice. Here, we show that the presence of unliganded ERα decreases vascular endothelial cell (EC) migration and proliferation, increases smooth muscle cell (SMC) proliferation, and increases inflammatory responses in cultured ECs and SMCs. Unliganded ERα also regulates many genes in vascular ECs and mouse aorta. Activation of ERα by E2 reverses the cell physiological effects of unliganded ERα, and promotes gene regulatory effects that are predicted to counter the effects of unliganded ERα. These results reveal that the unliganded form of ERα is not inert, but significantly impacts gene expression and physiology of vascular cells. Furthermore, they indicate that the cardiovascular protective effects of estrogen may be connected to its ability to counteract these effects of unliganded ERα.
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