Environmentally persistent alkylphenolic compounds are estrogenic.
Environmentally persistent alkylphenolic compounds are estrogenic.
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DOI：
10.1210/endo.135.1.8013351
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发表时间：
1994-07
期刊：
影响因子：
4.8
通讯作者：
Roger White;S. Jobling;S. Hoare;J. Sumpter;M. Parker
中科院分区：
文献类型：
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作者：
Roger White;S. Jobling;S. Hoare;J. Sumpter;M. Parker
我们表明，在各种商业产品中使用的以及在河水中发现的一些烷基酚化合物，对鱼类、鸟类和哺乳动物具有雌激素性。4-辛基酚（OP）、4-壬基酚、4-壬基苯氧羧酸和4-壬基酚二氧基酸均能刺激鳟鱼肝细胞中的卵黄蛋白原基因表达、转染细胞中的基因转录和乳腺癌细胞系的生长。这些化学物质中最有效的是OP，它能够刺激这些生物反应，其程度与17 -雌二醇本身相似，尽管浓度是17 -雌二醇的1000倍。烷基酚的作用是由雌激素受体介导的，因为它们的作用取决于它的存在，并被雌激素拮抗剂阻断。OP、4-壬基苯酚和4-壬基苯氧羧酸似乎具有内在的雌激素活性，因为它们竞争与雌激素受体结合。此外，它们很可能与17 β -雌二醇类似的激素结合区域相互作用，因为突变受体G-525R在雌激素结合方面存在缺陷，对OP也不敏感。与17 β -雌二醇一样，通过分析瞬时转染细胞中野生型和突变型受体的活性，可以判断OP能够刺激受体中转录激活功能TAF-1和TAF-2的活性。我们的研究结果的意义将在很大程度上取决于野生动物和人类接触这些雌激素烷基酚化合物的程度。
We show that a number of alkylphenolic compounds, used in a variety of commercial products and found in river water, are estrogenic in fish, birds, and mammals. 4-Octylphenol (OP), 4-nonylphenol, 4-nonylphenoxycarboxylic acid, and 4-nonylphenoldiethoxylate were each capable of stimulating vitellogenin gene expression in trout hepatocytes, gene transcription in transfected cells, and the growth of breast cancer cell lines. The most potent of the chemicals is OP, which was able to stimulate these biological responses to a similar extent as 17 beta-estradiol itself, albeit at a 1000-fold greater concentration. The action of alkylphenols is mediated by the estrogen receptor, as their effects depended on its presence and was blocked by estrogen antagonists. OP, 4-nonylphenol, and 4-nonylphenoxycarboxylic acid appear to possess intrinsic estrogenic activity, because they compete for binding to the estrogen receptor. Moreover, it is likely that they interact with a similar region of the hormone-binding domain as 17 beta-estradiol, because the mutant receptor G-525R, which is defective in estrogen binding, is also insensitive to OP. Like 17 beta-estradiol, OP is capable of stimulating the activity of both transcriptional activation functions, TAF-1 and TAF-2, in the receptor, as judged by analyzing the activity of the wild-type and mutant receptors in transiently transfected cells. The significance of our results will depend to a large extent on the degree of exposure of wildlife and humans to these estrogenic alkylphenolic compounds.