Estrogen receptors α and β have similar activities in multiple endothelial cell pathways
Estrogen receptors α and β have similar activities in multiple endothelial cell pathways
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DOI：
10.1210/en.2002-220356
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Adelman, SJ
中科院分区：
文献类型：
--
作者：
Evans, MJ;Harris, HA;Adelman, SJ
血管细胞中雌激素受体α (erα)和erβ的存在大大增加了心血管系统中潜在雌激素调节途径的复杂性。本研究利用腺病毒载体对人脐静脉内皮细胞进行工程化，使其表达erα或erβ。研究人员比较了erα和erβ在三种不同基因调控途径中的活性，包括抑制il -1 β诱导e -选择素的表达，抑制基底内皮素-1的产生，以及诱导两种基质稳定酶的能力：组织转谷氨酰胺酶和赖氨酸氧化酶家族的一种新成员。两种er在这些终点上都有活性，尽管erβ通常不如erα有效。由于没有一类基因调控可以区分erα和erβ的活性，我们鉴定了一种新的类固醇（7α -噻吩基- e2），它与erα和erβ具有相似的亲和力，但在所有这些内皮反应中都具有erα激动剂和erβ拮抗剂的作用。这种受体亚型选择活性模式并非内皮细胞所独有，但在代谢活跃的HepG2细胞中也可见到，表明其在体内的潜在效用。内皮反应面板与选择性调节剂相结合，应该提供一种方法来表征erα和erβ在内皮细胞体内的作用。
The presence of both estrogen receptor alpha (ERalpha) and ERbeta in vascular cells has greatly increased the complexity of potential estrogen regulatory pathways in the cardiovascular system. Here, human umbilical vein endothelial cells were engineered using adenovirus vectors to express either ERalpha or ERbeta. The activities of ERalpha and ERbeta were compared in three distinct gene regulatory pathways, including inhibition of IL-1beta induction of E-selectin expression, inhibition of basal endothelin-1 production, and the ability to induce two matrix-stabilizing enzymes: tissue transglutaminase and a novel member of the lysyl oxidase family. Both ERs were active on these end points, although ERbeta was typically less efficacious than ERalpha. As no class of gene regulation could differentiate ERalpha from ERbeta activity, we characterized a novel steroid (7alpha-thiophenyl-E2) that bound with similar affinities to ERalpha and ERbeta, but functioned as an ERalpha agonist and ERbeta antagonist for all of these endothelial responses. This pattern of receptor subtype-selective activity was not unique to endothelial cells, but was also seen in metabolically active HepG2 cells, suggesting potential in vivo utility. The panel of endothelial responses coupled with a selective modulator should provide a means to characterize the roles of ERalpha and ERbeta in endothelial cells in vivo.