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BioMed Research International
Volume 2013 (2013), Article ID 524324, 9 pages
http://dx.doi.org/10.1155/2013/524324
Research Article

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

Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia

Received 27 August 2013; Accepted 28 September 2013

Academic Editor: Robert M. Starke

Copyright © 2013 Jian Tu and Nurul F. Jufri. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 (ERβ) and G-protein-coupled receptor 1 (GPER1) were immunocytochemically identified in human cerebral vascular endothelial cells (HCVECs). ERβ was mainly located at the nuclei of the cells while GPER1 was located at the plasma membrane. Interaction events between 17β-estradiol and ERβ or GPER1 in HCVECs were evaluated by in situ proximity ligation assay. The number of interaction events between 17β-estradiol and ERβ was positively correlated with 17β-estradiol concentrations ( , ). The interaction events between 17β-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.