Peking University, Beijing, China.
Chemosphere. 2010 Jul;80(5):608-12. doi: 10.1016/j.chemosphere.2010.04.010. Epub 2010 May 6.
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.
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。
