Ability of structurally diverse natural products and synthetic chemicals to induce gene expression mediated by estrogen receptors from various species
Ability of structurally diverse natural products and synthetic chemicals to induce gene expression mediated by estrogen receptors from various species
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DOI：
10.1016/s0960-0760(02)00159-0
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发表时间：
2002-10-01
影响因子：
4.1
通讯作者：
Zacharewski, TR
中科院分区：
文献类型：
--
作者：
Matthews, JB;Fertuck, KC;Zacharewski, TR
研究了14种结构不同的雌激素化合物诱导不同物种雌激素受体介导的报告基因表达的能力。MCF-7细胞用Gal 4调节的荧光素酶报告基因瞬时转染（17 m5-G-Luc）和Gal 4-ER嵌合受体，其含有人α-受体的D、E和F结构域（Gal 4-hER α def），小鼠α（Gal 4-mER α def），小鼠P（Gal 4-mER β def）、鸡（Gal 4-cER α def）、绿色变色龙（Gal 4-aER α def）、非洲爪蟾（Gal 4-xER β def）或虹鳟α ER（Gal 4-rtER α def）。17 β-雌二醇（E2）诱导报告基因表达的功效在不同构建体中总体相似，EC 50值范围为0.05至0.7 nM。然而，Gal 4-rtERalphadef在37 ℃下的EC 50值为28 nNt，尽管在20 ℃下观察到的EC 50值为1 nM。尽管E2治疗的ER之间的类似的反应，许多差异，观察到其他结构不同的化学品的反应的幅度。例如，香豆雌酚诱导的Gal 4-mER β def和Gal 4-aER def介导的报告基因表达分别是其他Gal 4-ER介导的报告基因表达的164倍和8倍。同样，与其他Gal 4-ER的结果相反，α-玉米赤霉烯醇在比E2更低的浓度下始终诱导Gal 4-rtER alphadef介导的报告基因活性。总之，结果表明，所选的雌激素化合物表现出不同的能力，诱导报告基因活性介导的ER从不同的脊椎动物物种。这些数据还强调了在检查rtER α介导的活性时孵育温度的重要性。(C)2002爱思唯尔科技有限公司。保留所有权利。
The ability of 14 structurally diverse estrogenic compounds to induce reporter gene expression mediated by estrogen receptors (ERs) from different species was examined. MCF-7 cells were transiently transfected with a Gal4-regulated luciferase reporter gene (17m5-G-Luc) and Gal4-ER chimeric receptors containing the D, E and F domains of the human alpha (Gal4-hERalphadef), mouse alpha (Gal4-mERalphadef), mouse P (Gal4-mERbetadef), chicken (Gal4-cERalphadef), green anole (Gal4-aERalphadef), Xenopus (Gal4-xERdef) or rainbow trout alpha ERs (Gal4-rtERalphadef). The efficacy of 17beta-estradiol (E2) in inducing reporter gene expression was similar among the different constructs overall, with EC50 values ranging from 0.05 to 0.7 nM. However, Gal4-rtERalphadef had an EC50 value at 37degreesC of 28 nNt, though at 20degreesC an EC50 value of I nM was observed. Despite a similar response to E2 treatment among the ERs, many differences were observed in the magnitude of the response to other structurally diverse chemicals. For example, coumestrol induced Gal4-mERbetadef- and Gal4-aERdef-mediated reporter gene expression 164- and 8-fold greater, respectively, than mediated with the other Gal4-ERs. As well, in contrast to results with other Gal4-ERs, alpha-zearalenol consistently induced Gal4-rtERalphadef-mediated reporter gene activity at lower concentrations than did E2. Overall, the results demonstrate that selected estrogenic compounds exhibit a differential ability to induce reporter gene activity mediated by ERs from different vertebrate species. These data also highlight the importance of incubation temperature when examining rtERalpha-mediated activity. (C) 2002 Elsevier Science Ltd. All rights reserved.