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Little is known about estrogen receptors and their signaling mechanisms in human cerebral vascular endothelial cells, which is important for understanding cerebral aneurysm pathogenesis in menopausal and postmenopausal women. Estrogen receptor beta (ER  β  ) and G-protein-coupled receptor 1 (GPER1) were immunocytochemically identified in human cerebral vascular endothelial cells (HCVECs). ER  β   was mainly located at the nuclei of the cells while GPER1 was located at the plasma membrane. Interaction events between 17  β  -estradiol and ER  β   or GPER1 in HCVECs were evaluated by  in situ  proximity ligation assay. The number of interaction events between 17  β  -estradiol and ER  β   was positively correlated with 17  β  -estradiol concentrations ( r  = 0.9614,  P  < 0.01). The interaction events between 17  β  -estradiol and GPER1 were dose responsive. Our data support HCVECs to serve as a suitable cellular model for studying cerebral aneurysm pathogenesis in menopausal and postmenopausal women. Subtypes of estrogen receptors and their signaling mechanisms identified in HCVECs could be applicable for developing estrogen-like compounds to specifically bind to a subtype of estrogen receptors with greater specific action on the cerebral arteries, without the estrogen-dependent side effects on the reproductive organs, to prevent cerebral aneurysm formation in menopausal and postmenopausal woman.

biomed research international

Estrogen Signaling through Estrogen Receptor Beta and G-Protein-Coupled Estrogen Receptor 1 in Human Cerebral Vascular Endothelial Cells: Implications for Cerebral Aneurysms