Estrogen receptor beta dependent attenuation of cytokine-induced cyclooxygenase-2 by androgens in human brain vascular smooth muscle cells and rat mesenteric arteries.
Estrogen receptor beta dependent attenuation of cytokine-induced cyclooxygenase-2 by androgens in human brain vascular smooth muscle cells and rat mesenteric arteries.
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DOI：
10.1016/j.steroids.2012.04.013
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发表时间：
2012-07
期刊：
影响因子：
2.7
通讯作者：
Gonzales RJ
中科院分区：
文献类型：
--
作者：
Zuloaga KL;O'Connor DT;Handa RJ;Gonzales RJ
在病理生理条件下，雄激素可能对血管系统有保护作用。我们过去的研究表明，在细胞因子、内毒素或缺氧刺激下，人血管平滑肌细胞中的二氢睾酮（DHT）以雄激素受体（AR）不依赖的方式降低环氧化酶-2 （COX-2）的表达。经典的DHT被认为是一种纯AR激动剂；然而，它可以内源性代谢为5α-雄甾烷-3β， 17β-二醇（3β-二醇），最近被证明是一种选择性雌激素受体（ERβ）激动剂。因此，我们假设DHT在细胞因子刺激后的抗炎特性是通过ERβ介导的。以人脑血管平滑肌细胞（HBVSMC）为实验对象，研究DHT对IL-1β诱导的COX-2表达的影响是通过AR还是ERβ介导的。DHT代谢为3β-二醇是HBVSMC的一个可行途径，因为3β-二醇合成和代谢所需的酶[3 α -羟基类固醇脱氢酶（HSD）， 3β-HSD, 17β-HSD， CYP7B1]的mRNA被检测到。同时检测AR、ERα、ERβ mRNA的表达。当应用于HBVSMC时，DHT （10 nM; 18 h）减弱il -1β诱导的COX-2蛋白表达的增加。AR拮抗剂比卡鲁胺不能阻断DHT降低COX-2的能力。非选择性雌激素受体拮抗剂ICI 182780 （1 μM）和选择性ERβ拮抗剂PHTPP （1 μM）均抑制DHT的作用，提示DHT的作用是由ERβ介导的。在HBVSMC和大鼠肠系膜动脉中，3β-二醇，类似DHT，降低细胞因子诱导的COX-2水平。总之，DHT似乎通过代谢3β-二醇和激活ERβ来防止血管炎症的进展。
Androgens may provide protective effects in the vasculature under pathophysiological conditions. Our past studies have shown that dihydrotestosterone (DHT) decreases expression of cyclooxygenase-2 (COX-2) during cytokine, endotoxin, or hypoxic stimulation in human vascular smooth muscle cells, in an androgen receptor (AR)-independent fashion. Classically DHT is regarded as a pure AR agonist; however, it can be endogenously metabolized to 5α-androstane-3β, 17β-diol (3β-diol), which has recently been shown to be a selective estrogen receptor (ERβ) agonist. Therefore, we hypothesized that DHT’s anti-inflammatory properties following cytokine stimulation are mediated through ERβ. Using primary human brain vascular smooth muscle cells (HBVSMC), we tested whether DHT’s effect on IL-1β induced COX-2 expression was mediated via AR or ERβ. The metabolism of DHT to 3β-diol is a viable pathway in HBVSMC since mRNA for enzymes necessary for the synthesis and metabolism of 3β-diol [3alpha-hydroxysteroid dehydrogenase (HSD), 3β-HSD, 17β-HSD, CYP7B1] was detected. In addition, the expression of AR, ERα, and ERβ mRNA was detected. When applied to HBVSMC, DHT (10 nM; 18 h) attenuated IL-1β-induced increases in COX-2 protein expression. The AR antagonist bicalutamide did not block DHT’s ability to reduce COX-2. Both the non-selective estrogen receptor antagonist ICI 182,780 (1 μM) and the selective ERβ antagonist PHTPP (1 μM) inhibited the effect of DHT, suggesting that DHT actions are ERβ-mediated. In HBVSMC and in rat mesenteric arteries, 3β-diol, similar to DHT, reduced cytokine-induced COX-2 levels. In conclusion, DHT appears to be protective against the progression of vascular inflammation through metabolism to 3β-diol and activation of ERβ.
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DOI：
10.1038/jcbfm.2009.226
发表时间：
2010-03
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
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DOI：
10.1038/jcbfm.2008.115
发表时间：
2009-02
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Kuiper, GGJM;Lemmen, JG;Gustafsson, JÄ
通讯作者：
Gustafsson, JÄ
睾酮通过抑制内皮细胞中的核因子-κ B 减轻肿瘤坏死因子-α 介导的组织因子途径抑制剂下调
影响因子：
2.9
作者：
Jin, Hong;Qiu, Wen-Bing;Tan, Xue-Rui
通讯作者：
Tan, Xue-Rui
影响因子：
3.5
作者：
Hatakeyama, H;Nishizawa, M;Uchida, K
通讯作者：
Uchida, K