Fujimoto Nariaki, Kitamura Shigeyuki
Department of Developmental Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University,1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
J Steroid Biochem Mol Biol. 2004 Jan;88(1):53-9. doi: 10.1016/j.jsbmb.2003.10.006.
There has been much discussion concerning endocrine disrupting chemicals suspected of exerting adverse effects in both wildlife and humans. Since the majority of these compounds are estrogenic, a large number of in vitro tests for estrogenic characteristics have been developed for screening purpose. One reliable and widely used method is the reporter gene assay employing estrogen receptors (ERs) and a reporter gene with a cis-acting estrogen responsive element (ERE). Other elements such as AP1 also mediate estrogenic signals and the manner of response could be quite different from that of ERE. Since this has yet to be explored, the ER mediated AP1 activity in response to a series of environmental estrogens was investigated in comparison with ERE findings. All the compounds exhibited estrogenic properties with ERE-luc and their AP1 responses were quite similar. These was one exception, however, p,p'-DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane) did not exert any AP1-luc activity, while it appeared to be estrogenic at 10(-7) to 10(-5)M with the ERE action. None of the compounds demonstrated ER beta:AP1 activity. These data suggest that significant differences can occur in responses through the two estrogen pathways depending on environmental chemicals.
关于怀疑对野生动物和人类均有不利影响的内分泌干扰化学物质，已经有很多讨论。由于这些化合物大多数具有雌激素活性，因此已经开发了大量用于筛选目的的雌激素特性体外试验。一种可靠且广泛使用的方法是利用雌激素受体（ERs）和带有顺式作用雌激素反应元件（ERE）的报告基因的报告基因检测法。其他元件如AP1也介导雌激素信号，其反应方式可能与ERE的反应方式有很大不同。由于尚未对此进行探索，因此与ERE的研究结果相比，研究了ER介导的AP1对一系列环境雌激素的反应活性。所有化合物对ERE-荧光素酶（ERE-luc）均表现出雌激素特性，且它们的AP1反应非常相似。然而，有一个例外，即p,p'-滴滴涕（1,1,1-三氯-2,2-双（对氯苯基）乙烷）没有任何AP1-荧光素酶（AP1-luc）活性，而在10^(-7)至10^(-5)M浓度下，它通过ERE作用似乎具有雌激素活性。没有一种化合物表现出ERβ:AP1活性。这些数据表明，取决于环境化学物质，通过两种雌激素途径的反应可能会出现显著差异。
