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在大鳞大麻哈鱼(Oryzias latipes)体内和体外,17α-雌二醇的雌激素效应。

In vitro and in vivo estrogenic effects of 17alpha-estradiol in medaka (Oryzias latipes).

机构信息

Peking University, Beijing, China.

出版信息

Chemosphere. 2010 Jul;80(5):608-12. doi: 10.1016/j.chemosphere.2010.04.010. Epub 2010 May 6.

Abstract

17alpha-Estradiol (17alpha-E2), the stereoisomer of 17beta-estradiol (17beta-E2), is considered a weak estrogen in mammals. However, little is known about its estrogenic potency in teleost fish, even though 17alpha-E2 has been frequently detected in aquatic environment. To investigate the estrogenic activity of 17alpha-E2, an in vitro assay based on the ligand-dependent interaction between medaka estrogen receptor alpha (med-ERalpha) and coactivator was conducted. Japanese medaka (Oryziaslatipes) were exposed to 1, 10, 100, 1000 and 10000ng L(-1) 17alpha-E2 (actual concentrations of 1.91, 12.81, 96.24, 1045.15, and 9320.81ng L(-1), respectively) for 3 weeks, and expression for vitellogenins (VTG-I), Choriogenin H (CHG-H) and estrogen receptor alpha (ERalpha) mRNA in the livers was analyzed by quantitative real-time RT-PCR (Q-RT-PCR). The in vitro study showed that the EC(50) of 17alpha-E2 was 114.10nM, which was 30 times less potent than that of 17beta-E2 (3.80nM). Dose-dependent induction of gene expression of VTG-I, CHG-H and ERalpha were observed. The benchmark dose (BMD) values for VTG-I, CHG-H and ERalpha were 44.16ng L(-1), 15.25ng L(-1) and 66.03ng L(-1), which were about 11-, 17- and 14-times less potent than that of 17beta-E2, respectively. Comparing this study with those reported previously in mammals, it is suggested that fish species may be more susceptive to 17alpha-E2 than mammals.

摘要

17α-雌二醇(17α-E2)是 17β-雌二醇(17β-E2)的立体异构体,被认为是哺乳动物中的一种弱雌激素。然而,尽管 17α-E2 经常在水生环境中被检测到,但人们对其在鱼类中的雌激素活性知之甚少。为了研究 17α-E2 的雌激素活性,我们进行了一项基于 medaka 雌激素受体 alpha(med-ERalpha)与共激活子之间配体依赖性相互作用的体外测定。将日本青鳉(Oryzias latipes)暴露于 1、10、100、1000 和 10000ng/L-1 的 17α-E2(实际浓度分别为 1.91、12.81、96.24、1045.15 和 9320.81ng/L-1)中 3 周,并用定量实时 RT-PCR(Q-RT-PCR)分析肝脏中 vitellogenins(VTG-I)、Choriogenin H(CHG-H)和雌激素受体 alpha(ERalpha)mRNA 的表达。体外研究表明,17α-E2 的 EC50 为 114.10nM,比 17β-E2(3.80nM)的活性低 30 倍。观察到 VTG-I、CHG-H 和 ERalpha 的基因表达呈剂量依赖性诱导。VTG-I、CHG-H 和 ERalpha 的基准剂量(BMD)值分别为 44.16ng/L-1、15.25ng/L-1 和 66.03ng/L-1,分别比 17β-E2 的活性低约 11、17 和 14 倍。将本研究与以前在哺乳动物中报道的研究进行比较,表明鱼类可能比哺乳动物更容易受到 17α-E2 的影响。

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