Analysis of endocrine-disrupting activities of environmental chemicals that associate with thyroid-hormone-binding proteins

与甲状腺激素结合蛋白相关的环境化学物质的内分泌干扰活性分析

• 批准号: 13559001
• 负责人: YAMAUCHI Kiyoshi
• 金额: $ 6.02万
• 依托单位: Shizuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13559001/
• 关键词: Environmental chemicals; Thyroid hormone; Receptor; Binding protein; Amphibian

We investigated the effects of phenolic and phenol compounds on 3,3',5-[^<125>I]triiodothyronine ([^<125>I]T_3) binding to purified Xenopus laevis transthyretin (xTTR) and to the ligand-binding domain of X. laevis thyroid hormone receptor β (xTR LBD), on T_3-induced metamorphosis in X. laevis tadpoles and on the induction of T_3-dependent reporter gene in a X. laevis cell line. Of the halogenated phenolic and phenol compounds tested, 3,3',5-trichlorobisphenol A and 2,4,6-triiodophenol, respectively, were the most potent competitors of [^<125>I]T_3 binding to both xTTR and xTR LBD. Most of the halogenated compounds had stronger interactions with xTTR than with xTR LBD. Generally, chlorinated derivatives with a greater degree of chlorination were more efficient competitors of T_3 binding to xTTR and xTR LBD. Structures with a halogen in either ortho positions or in both ortho positions, with respect to the hydroxy group, were more efficient competitors. 3,3',5-Trichlorobisphenol A and 2,4,6-triiodophenol acted as T_3 antagonists in the X laevis tadpole metamorphosis assay. Interestingly, o-t-butylphenol and 2-isopropylphenol, for which xTTR and xTR LBD had weak or no significant affinity, showed T_3 antagonist activity in the metamorphosis assay. T_3 antagonist activities of all these chemicals except for o-t-butylphenol were verified by T_3-dependent reporter gene assay. Our results suggest that some phenolic and phenol compounds target the process of T_3 binding to xTTR and xTR and/or an unknown process, and that they interfere with the intracellular T_3 signaling pathway.

我们研究了酚类和苯酚化合物对3,3、5- [^<25> i]三碘甲氨酸（[^<25> i] T_3）与纯化的Xenopus evis transthyretin（XTTR）和配体结合域结合的影响X. laevis激素受体β（XTR LBD）的X.33诱导的变态。是[^<125 I] XTR LBD的最有效的竞争者。 LBD。 X LAEVIS tATPOLE ETAMORPHOSIS分析。 。

项目成果

Kiyoshi YAMAUCHI: "Characterization of Xenopus cytosolic thyroid-hormone-binding protein (xCTBP) with aldehyde dehydrogenase activity"Chemico-Biological Interactions. 130-132・1-3. 309-321 (2001)

Kiyoshi YAMAUCHI：“爪蟾胞质甲状腺激素结合蛋白（xCTBP）与醛脱氢酶活性的表征”130-132・1-3（2001）。

In vitro and in vivo analysis of the thyroid disrupting activities of phenolic and phenol compounds in Xenopus laevis.

• DOI: 10.1093/toxsci/kfi049
• 发表时间: 2005-03
• 期刊: Toxicological sciences : an official journal of the Society of Toxicology
• 作者: Yumiko Kudo;K. Yamauchi

Akinori Ishihara: "The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor"General and Comparative Endocrinology. 134・1. 36-43 (2003)

Akinori Ishihara：“内分泌干扰化学物质对甲状腺激素与日本鹌鹑运甲状腺素蛋白和甲状腺激素受体结合的影响”普通和比较内分泌学134・1（2003）。

Kiyoshi Yamauchi: "Competitive interactions of chlorinated phenol compounds with 3,3',5-triiodothyronine binding to transthyretin"Toxicology and Applied Pharmacology. 187・2. 110-117 (2003)

Kiyoshi Yamauchi：“氯化苯酚化合物与3,3,5-三碘甲状腺原氨酸与转甲状腺素蛋白结合的竞争性相互作用”毒理学和应用药理学187・2（2003）。

Akinori Ishihara: "Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors"Molecular and Cellular Endocrinology. 199・1-2. 105-117 (2003)

Akinori Ishihara：“内分泌干扰化学物质：甲状腺激素与甲状腺素运载蛋白和甲状腺激素受体结合的干扰”分子和细胞内分泌学199・1-117（2003）。