Identification of authentic estrogen receptor in cultured endothelial cells - A potential mechanism for steroid hormone regulation of endothelial function

Identification of authentic estrogen receptor in cultured endothelial cells - A potential mechanism for steroid hormone regulation of endothelial function
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DOI:
10.1161/01.cir.94.4.727
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发表时间:
1996-08-15
期刊:
影响因子:
37.8
通讯作者:
Vaughan, DE
Vaughan, DE
中科院分区:
医学1区
文献类型:
--
作者:
Venkov, CD;Rankin, AB;Vaughan, DE

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背景雌激素在女性冠心病(CHD)的延迟表达中起主要作用,最近的数据表明绝经后雌激素治疗可使冠心病的发病率降低约40%。尽管雌激素对血压、碳水化合物和脂质代谢以及凝血有影响,但其发挥这种益处的机制尚不清楚。我们假设雌激素降低冠心病发病率的作用至少部分是由于其对内皮细胞功能的影响。方法和结果本研究采用免疫印迹和mRNA分析的方法检测了人主动脉和脐静脉内皮细胞和牛主动脉内皮细胞中雌激素受体(er)的存在。电泳迁移率转移测定也进行了确定dna结合性质的假设的er。三种内皮细胞类型的核提取物均含有67-kD蛋白,该蛋白可与内质网不同结构域的抗内质网单克隆抗体反应。每一种类型的细胞都表达特异性结合雌激素反应元件的蛋白质。最后,Northern blots证实内皮细胞表达了大量的ER mRNA。结论内皮细胞具有雌激素调控靶基因转录的潜能。该受体在牛和人内皮细胞中的进化保护表明雌激素调节内皮功能的共同机制。
Background Estrogen plays a major role in the delayed expression of coronary heart disease (CHD) in women, and recent data indicate that postmenopausal estrogen therapy reduces the incidence of CHD by >40%. The mechanism or mechanisms through which estrogen exerts this benefit are unknown, although effects on blood pressure, carbohydrate and lipid metabolism, and coagulation have been suggested. We hypothesized that at least part of the effect of estrogen in reducing the incidence of CHD is due to an effect on endothelial cell function.Methods and Results In the present study, we examined human aortic and umbilical vein endothelial cells and bovine aortic endothelial cells for the presence of estrogen receptors (ERs) through immunoblot and mRNA analyses. Electrophoretic mobility shift assays were also performed to determine the DNA-binding properties of the putative ERs. Nuclear extracts from all three endothelial cell types were found to contain a 67-kD protein that reacted with anti-ER monoclonal antibodies specific to different domains of the ERs. Each of these types of cells expresses proteins that bind specifically to consensus estrogen-responsive elements. Finally, Northern blots verified that endothelial cells express abundant amount of mRNA for the ER.Conclusions These data indicate that endothelial cells constitutively possess the potential for transcriptional regulation of target genes by estrogen. The evolutionary conservation of this receptor in bovine and human endothelial cells suggests a common mechanism for estrogen regulation of endothelial function.