Unequivocal estrogen receptor-binding affinity of phthalate esters featured with ring hydroxylation and proper alkyl chain size.
Unequivocal estrogen receptor-binding affinity of phthalate esters featured with ring hydroxylation and proper alkyl chain size.
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DOI：
10.1016/j.abb.2004.07.028
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发表时间：
2004-11
影响因子：
3.9
通讯作者：
C. Toda;Yoshinori Okamoto;K. Ueda;K. Hashizume;K. Itoh;N. Kojima
中科院分区：
文献类型：
--
作者：
C. Toda;Yoshinori Okamoto;K. Ueda;K. Hashizume;K. Itoh;N. Kojima
增塑剂邻苯二甲酸酯（PE）对健康的影响是一个有争议的话题。PE很可能具有雌激素样作用，但许多研究者对PE的药效研究结果仍不一致，其内分泌干扰机制仍有待阐明。在这里，我们表明，PE获得明确的结合亲和力的人雌激素受体（ER）通过环羟基化，这是可能的环境中，并通过代谢。出乎意料的是，羟基化PE（PEs-OH）的亲和力通过酯烷基链的延长和支化而增强。烷基链长度超过6个碳的PEs-OH可以寻找到短链PEs-OH所不能达到的新的结合位点。最强的ER-结合亲和力之间的测试PEs-OH是接近的己烯雌酚，最有效的合成ER-粘合剂。环羟基化可能为阐明PE的内分泌干扰机制提供新的线索。
The effect of plasticizers phthalate esters (PEs) on health is a controversial subject. PEs are likely to be estrogenic, but the results on the potency obtained by many investigators are still inconsistent and the endocrine disrupting mechanism remains to be clarified. Here, we show that PEs acquire unequivocal binding affinities for human estrogen receptors (ERs) through ring hydroxylation that is possible in the environment and through metabolism. Unexpectedly, the acquired affinities of hydroxylated PEs (PEs-OH) were enhanced by elongation and branching of the ester alkyl chains. PEs-OH with alkyl chains more than six carbons may grope for a new binding site, which is inaccessible to PEs-OH with short chains. The strongest ER-binding affinity among the tested PEs-OH was close to that of diethylstilbestrol, the most potent synthetic ER-binder. Ring hydroxylation would be a new clue to the clarification of the endocrine disruption mechanism of PEs.