Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia.
Biomed Res Int. 2013;2013:524324. doi: 10.1155/2013/524324. Epub 2013 Nov 12.
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 (r = 0.9614, P < 0.01). 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.
关于人类脑血管内皮细胞中的雌激素受体及其信号机制知之甚少，而这对于理解绝经后和绝经后女性的颅内动脉瘤发病机制至关重要。免疫细胞化学鉴定了人类脑血管内皮细胞（HCVEC）中的雌激素受体β（ERβ）和 G 蛋白偶联受体 1（GPER1）。ERβ 主要位于细胞的细胞核中，而 GPER1 则位于质膜上。通过原位接近连接测定评估了 17β-雌二醇与 ERβ 或 GPER1 在 HCVEC 中的相互作用事件。17β-雌二醇与 ERβ 的相互作用事件数量与 17β-雌二醇浓度呈正相关（r = 0.9614，P < 0.01）。17β-雌二醇与 GPER1 的相互作用事件呈剂量反应关系。我们的数据支持 HCVEC 作为研究绝经后和绝经后女性颅内动脉瘤发病机制的合适细胞模型。在 HCVEC 中鉴定的雌激素受体亚型及其信号机制可用于开发类似雌激素的化合物，使其特异性结合具有更大特异性作用于脑动脉的雌激素受体亚型，而不会对生殖器官产生雌激素依赖性副作用，从而预防绝经后和绝经后女性的脑动脉瘤形成。
