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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11839009/
• 关键词: Thyroid Hormone; Endocrine Disrupting Chemicals; Hormone Binding Proteins; Synthetic Xencestrogens; Alkylated Phenols; chichen; Amphibian; 核内受容体; ウシガエル; 結合蛋白質

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，某些外源性内分泌破坏化学物质，多面化芳族碳氢化合物，例如多氯联苯二苯基，Dibenzo-P-二恶英及其羟基化化合物，可能会影响哺乳动物的甲状腺甲状腺系统。然而，在大的脑素中，化学物质与甲状腺素的结合的影响低于其他脊椎动物，因为甲状腺激素结合的蛋白，对上述化学物质具有很高亲和力的甲状腺素是造成甲状腺大的甲状腺酮马酮马龙结合活性，在甲状腺，鸟类，鸟类，鸟类，鸟类，斑点，斑点，斑点和鱼类。在本研究中，我们研究了几类化学物质与两栖动物和鸟类经甲状腺素蛋白和甲状腺受体的相互作用。在存在工业，医学或农业化学化学物质的情况下，将纯化的经硫代蛋白与[^<125> i] -3,3,5'-Triioodothonine（T_3）一起孵育。为了阐明化学物质与经硫代蛋白的相互作用的模式，通过SCATCHARD图确定了明显的解离常数A…更最大的结合能力。在存在各种浓度的某些化学物质的情况下，还研究了对红细胞的T_3摄取。合成雌激素，二乙基苯甲酸酯的潜力是T_3的2-50倍，用于t_3的[^<125> i] T_3的T_3。农业化学物质，耐氧酚和五氯苯酚也是[^<125> i] T3与经硫代蛋白结合的显着抑制剂。 SCATCHATD分析表明，这些化学物质的结合模式具有竞争力。有趣的是，一种生物脱叶曲酚激活[^<125> i] T_3与牛蛙经胸蛋白结合，在10^<-9>到10^<-9>至10^<-6> M. [^<125> i] T_3与鸡经硫素的影响受到大多数化学物质的影响。但是，甲状腺受体表现出非常弱或很少的亲和力。总之，经硫代蛋白以特定方式识别几种内分泌破坏化学物质。某些雌激素化学物质与甲状腺素蛋白的结合不仅可以调节它们进入细胞的访问，还可以改变细胞外T_3的自由浓度

项目成果

Kiyoshi Yamauchi: "Effect of diethylstilbestrol on thyroid-hormone-binding to amphibian transthyretin"General and Comparative Endocrinology. 119. 329-339 (2000)

Kiyoshi Yamauchi：“己烯雌酚对两栖动物甲状腺激素结合的甲状腺激素的影响”普通和比较内分泌学。

Kiyoshi Yamauchi: "Xenopus cytosolic thyroid hormone-binding protein (xCTBP) is aldehyde dehydrogenase catalizing the formation retinoic acid"The Journal of Biological Chemistry. 274・13. 8460-8469 (1999)

Kiyoshi Yamauchi：“爪蟾胞质甲状腺激素结合蛋白（xCTBP）是催化视黄酸形成的醛脱氢酶”《生物化学杂志》274・13（1999）。

Kiyoshi Yamauchi: "Xenopus cytosolic thyroid hormone-binding protein (xCTBP) is aldehyde dehydrogenase catalysing the formation of retinoic acid"The Journal Biological Chemistry. 274(13). 8460-8469 (1999)

Kiyoshi Yamauchi：“非洲爪蟾胞质甲状腺激素结合蛋白（xCTBP）是催化视黄酸形成的醛脱氢酶”《生物化学》杂志。

Kiyoshi Yamauchi: "Effect of diethylstilbestrol on thyroid-hormone-binding to amphibian transthyretins"General and Comparative Endocrinology. 119(3). 329-339 (2000)

Kiyoshi Yamauchi：“己烯雌酚对两栖动物甲状腺激素结合的甲状腺激素的影响”普通和比较内分泌学。

Kiyeshi Yamauchi: "Effect of diethylstilbestrol on thyroid hormone binding to amphibian Transthyretin"General and Comparative Endocrinology. 119・3. 329-339 (2000)

Kiyeshi Yamauchi：“己烯雌酚对两栖动物甲状腺激素结合的甲状腺激素的影响”普通和比较内分泌学119・3（2000）。