Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.
Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.
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DOI：
10.1289/ehp.02110917
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发表时间：
2002-09
影响因子：
10.4
通讯作者：
Kortenkamp A
中科院分区：
文献类型：
--
作者：
Rajapakse N;Silva E;Kortenkamp A
许多人造雌激素化学品，即所谓的异种雌激素，效力较低，这一点被用来表明，接触个别化学品所产生的风险可以忽略不计。另一个用于消除对健康影响的担忧的论点是，内源性甾体雌激素对外源性雌激素的作用太强，不会显著促进雌激素效应。使用酵母报告基因分析与人类雌激素receptoralpha，我们测试了这些想法实验评估的能力，11种异种雌激素的组合，影响17 β-雌二醇的行动。值得注意的是，每种异种雌激素的水平远低于其无明显作用浓度（NOEC）。为了获得低效应的准确描述，我们记录了每种异种雌激素和17 β-雌二醇的浓度-反应关系。我们使用这些数据来预测整个浓度-反应曲线的混合物的异种雌激素与17 β-雌二醇，假设加性组合效应。在很大的浓度范围内，实验观察到的反应决定性地证实了模型的预测。11种异种雌激素的综合累加效应导致激素作用的显著增强，即使每种单一药剂的浓度低于其NOEC。我们的研究结果表明，即使是低于NOEC水平的异种雌激素，当它们与大量类似作用的化学品一起作用时，也不能认为对强效甾体雌激素没有影响。这些影响在多大程度上可以被具有抗雌激素活性的环境化学品所中和还有待观察。然而，潜在的人类和野生动物的反应诱导的外源性雌激素的叠加组合效应值得认真考虑。
The low potency of many man-made estrogenic chemicals, so-called xenoestrogens, has been used to suggest that risks arising from exposure to individual chemicals are negligible. Another argument used to dismiss concerns of health effects is that endogenous steroidal estrogens are too potent for xenoestrogens to contribute significantly to estrogenic effects. Using a yeast reporter gene assay with the human estrogen receptoralpha, we tested these ideas experimentally by assessing the ability of a combination of 11 xenoestrogens to affect the actions of 17ss-estradiol. Significantly, each xenoestrogen was present at a level well below its no-observed-effect concentration (NOEC). To derive accurate descriptions of low effects, we recorded concentration-response relationships for each xenoestrogen and for 17ss-estradiol. We used these data to predict entire concentration-response curves of mixtures of xenoestrogens with 17ss-estradiol, assuming additive combination effects. Over a large range of concentrations, the experimentally observed responses decisively confirmed the model predictions. The combined additive effect of the 11 xenoestrogens led to a dramatic enhancement of the hormone's action, even when each single agent was present below its NOEC. Our results show that not even sub-NOEC levels of xenoestrogens can be considered to be without effect on potent steroidal estrogens when they act in concert with a large number of similarly acting chemicals. It remains to be seen to what degree these effects can be neutralized by environmental chemicals with antiestrogenic activity. Nevertheless, potential human and wildlife responses induced by additive combination effects of xenoestrogens deserve serious consideration.
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影响因子：
10.4
作者：
Payne, J;Rajapakse, N;Wilkins, M;Kortenkamp, A
通讯作者：
Kortenkamp, A
影响因子：
9.8
作者：
Kortenkamp, A;Altenburger, R
通讯作者：
Altenburger, R
影响因子：
10.4
作者：
Miller, D;Wheals, BB;Sumpter, JP
通讯作者：
Sumpter, JP
影响因子：
4.8
作者：
Ramamoorthy, K;Wang, F;Safe, S
通讯作者：
Safe, S
影响因子：
4.1
作者：
Altenburger, R;Backhaus, T;Grimme, LH
通讯作者：
Grimme, LH