State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
Toxicol In Vitro. 2010 Feb;24(1):201-7. doi: 10.1016/j.tiv.2009.09.008. Epub 2009 Sep 16.
Some phenols have been suspected to modulate the endocrine systems of wildlife and humans, but less is known about their interactions with different types of nuclear receptors. In this study, the ability of 2-tert-butylphenol, 2-isopropylphenol, 4-tert-octylphenol (4-t-OP), 2,4-dichlorophenol (2,4-DCP), 3,4-dichlorophenol (3,4-DCP), pentachlorophenol (PCP), bisphenols A (BPA), tetrabromobisphenol A (TBBPA), tetrachlorobisphenol A (TCBPA) and 4-phenylphenol to activate estrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR) and estrogen-related receptor (ERR) were determined using a set of recombined yeast strains. It was found that 4-t-OP, 3,4-DCP, PCP, BPA, TBBPA, TCBPA and 4-phenylphenol were ERalpha agonists, while 4-t-OP, PCP and 4-phenylphenol showed ERalpha antagonistic activities. 2-tert-Butylphenol, 4-t-OP, 2-isopropylphenol, 2,4-DCP, 3,4-DCP, BPA, TCBPA and 4-phenylphenol were antagonists for AR, whereas none of the compounds studied were found to be an AR agonist. TCBPA, TBBPA and PCP were PR antagonists, and 2-tert-butylphenol, 3,4-DCP, 4-t-OP, 4-phenylphenol and 2-isopropylphenol were weak inhibitors on expression under control of the PR. None of the phenols were PR agonists. 2-tert-Butylphenol, 4-t-OP and PCP were ERRgamma inverse agonists, while 2,4-DCP, 3,4-DCP, PCP, BPA, TBBPA and TCBPA exhibited the ability to reverse the ERR inhibition induced by 4-hydroxytamoxifen. Based on the functional agonistic or antagonistic receptor-mediated effects, we further discussed the possible action mechanisms of these phenols as endocrine disrupting chemicals.
一些酚类物质已被怀疑能调节野生动物和人类的内分泌系统，但它们与不同类型核受体的相互作用知之甚少。在这项研究中，使用一组重组酵母菌株，测定了 2-叔丁基苯酚、2-异丙基苯酚、4-叔辛基苯酚（4-t-OP）、2,4-二氯苯酚（2,4-DCP）、3,4-二氯苯酚（3,4-DCP）、五氯苯酚（PCP）、双酚 A（BPA）、四溴双酚 A（TBBPA）、四氯双酚 A（TCBPA）和 4-苯基苯酚激活雌激素受体（ER）、雄激素受体（AR）、孕激素受体（PR）和雌激素相关受体（ERR）的能力。结果发现，4-t-OP、3,4-DCP、PCP、BPA、TBBPA、TCBPA 和 4-苯基苯酚是 ERalpha 激动剂，而 4-t-OP、PCP 和 4-苯基苯酚则表现出 ERalpha 拮抗活性。2-叔丁基苯酚、4-t-OP、2-异丙基苯酚、2,4-DCP、3,4-DCP、BPA、TCBPA 和 4-苯基苯酚是 AR 的拮抗剂，而研究的化合物中没有一种是 AR 激动剂。TCBPA、TBBPA 和 PCP 是 PR 的拮抗剂，而 2-叔丁基苯酚、3,4-DCP、4-t-OP、4-苯基苯酚和 2-异丙基苯酚则是 PR 表达的弱抑制剂。没有一种酚类物质是 PR 激动剂。2-叔丁基苯酚、4-t-OP 和 PCP 是 ERRgamma 反向激动剂，而 2,4-DCP、3,4-DCP、PCP、BPA、TBBPA 和 TCBPA 则表现出逆转 4-羟基他莫昔芬诱导的 ERR 抑制的能力。基于功能性激动或拮抗受体介导的作用，我们进一步讨论了这些酚类物质作为内分泌干扰物的可能作用机制。
