Effects of Endocrine Disrupting Chemicals on Thyroid Hormone Binding

内分泌干扰化学物质对甲状腺激素结合的影响

基本信息

批准号：
11839009
负责人：
YAMAUCHI Kiyoshi
金额：
$ 2.05万
依托单位：
Shizuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

It is well established that some exogenous endocrine disrupting chemicals, polyhalogenated aromatic hydrocarbons such as polychlorinated biphenyls, dibenzo-p-dioxins and their hydroxylated compounds, can affect a mammalian thyroid system. However, the impact of the chemicals' binding to transthyretin is lower in large eutherians than in other vertebrates, because a thyroid-hormone-binding protein, tranthyretin, which has an high affinity for the above chemicals, is responsible for major thyroid hormone-binding activity in plasma of rodents, birds, amphibians and fish. In the present study, we have investigated the interactions of several classes of chemicals with amphibian and avian transthyretins and thyroid receptors. Purified transthyretins were incubated with [^<125>I]-3,3,5'-triiodothyronine (T_3) in the presence of either an industrial, a medical or an agricultural chemical. To clarify the mode of interaction of the chemicals with transthyretins, apparent dissociation constants a … More nd maximum binding capacities were determined by Scatchard plots. [^<125>I]T_3 uptake into red blood cells was also investigated in the presence of various concentrations of some chemicals. A synthetic estrogen, diethylstilbestrol, was 2-50 times more potent than T_3 to displace [^<125>I]T_3 from transthyretin. Agricultural chemicals, ioxynil and pentachlorophenol, were also significant inhibitors on [^<125>I]T3 binding to transthyretins. Scatchatd analyzes indicated that the binding mode of these chemicals was competitive. Interestingly, a miticide dicofol activated [^<125>I]T_3 binding to bullfrog transthyretin up to 2-fold at 10^<-9> to 10^<-6> M. [^<125>I]T_3 binding to chicken transthyretin was profoundly affected by most chemicals investigated here, compared with bullfrog transthyretin which is strong T_3 carrier. However, thyroid receptors showed very weakly or little affinity forthese chemicals. In conclusion, transthyretins recognized several endocrine disrupting chemicals in a species-specific manner. The binding of some estrogenic chemicals to transthyretin may modulate not only their access to the cells but also change the free concentration of extracellular T_3 Less

众所周知的是，多面化的芳族烃的外源内分泌，例如多钙化的LS，Dibenzo-P-Dioxins及其羟基化合物，可以影响哺乳动物的甲状腺素系统中的大型甲蛋白素比其他verteperins较低。 - 在啮齿动物的血浆中，构成蛋白质的甲状腺素素，用于甲状腺激素结合活性，我们具有化学物质与两栖动物和鸟类经甲状腺素的隔膜相互作用，并用[^<125> i] -3 <125> i] -3 <125> i] -35> i] -355> i] ，在存在工业，医学或农业化学的情况下，3,5'-Triiodothyronine（T_3）。在某些化学物质的存在下，还研究了血液的0倍MITICIDE DICOFOL激活[^<125> i] T_3在10^<-9>时与牛蛙transthyretin结合2倍至10^<-6> m。大多数化学物质在这里研究了强烈的T_3携带者，甲状腺受体非常或少于甲状腺素。细胞外T_3的浓度更少