ENVIRONMENTALLY PERSISTENT ALKYLPHENOLIC COMPOUNDS ARE ESTROGENIC
ENVIRONMENTALLY PERSISTENT ALKYLPHENOLIC COMPOUNDS ARE ESTROGENIC
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DOI：
10.1210/en.135.1.175
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发表时间：
1994-07-01
期刊：
影响因子：
4.8
通讯作者：
PARKER, MG
中科院分区：
文献类型：
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作者：
WHITE, R;JOBLING, S;PARKER, MG
我们表明，一些烷基酚类化合物，用于各种商业产品和河水中发现，在鱼类，鸟类和哺乳动物雌激素。4-辛基酚（OP），4-壬基酚，4-壬基苯氧基羧酸，和4-壬基酚二乙氧基化物都能够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。最有效的化学物质是OP，它能够刺激这些生物反应，其程度与17 β-雌二醇本身相似，尽管浓度高出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，并被雌激素受体阻断剂阻断。OP、4-壬基酚和4-壬基苯氧基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，它们可能与雌激素结合结构域的类似区域相互作用，如17 β-雌二醇，因为突变型受体G-525 R，其在雌激素结合方面有缺陷，也对OP不敏感。与17 β-雌二醇一样，OP能够刺激受体中转录激活功能TAF-1和TAF-2的活性，通过分析瞬时转染细胞中野生型和突变型受体的活性来判断。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暴露于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 antago-nists. 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.