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

Research Project

Project/Area Number 13559001
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 広領域
Research InstitutionShizuoka University

Principal Investigator

YAMAUCHI Kiyoshi  Shizuoka University, Faculty of Science, Professor, 理学部, 教授 (50201827)

Co-Investigator(Kenkyū-buntansha) ROBERT.D. Denver  ミシガン大学, 生物学部, 助教授
DENVER Roberst J.  The University of Michigan, Department of Biology, Associate Professor
竹内 浩昭  静岡大学, 理学部, 助教授 (90216854)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥9,400,000 (Direct Cost: ¥9,400,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
KeywordsEnvironmental chemicals / Thyroid hormone / Receptor / Binding protein / Amphibian
Research Abstract

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.

Report

(4 results)
  • 2004 Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004 Other

All Journal Article (5 results) Publications (7 results)

  • [Journal Article] Low-temperature arrest of the triiodothyronine-dependent transcription in Rana catesbeiana red blood cells2005

    • Author(s)
      Tomonori Murata
    • Journal Title

      Endocrinology 146・1

      Pages: 256-264

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro and in vivo analysis of the thyroid disrupting activities of phenolic and phenol compounds in Xenopus laevis.2005

    • Author(s)
      Yumiko Kudo
    • Journal Title

      Toxicological Science 84・1

      Pages: 29-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Low-temperature arrest of the triiodothyronine-dependent transcription in Rana catesbeiana red blood cells.2005

    • Author(s)
      Tomonori Murata
    • Journal Title

      Endocrinology 146・1

      Pages: 256-264

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Characteristics of 3,5,3'-tri-iodothyronine (T3)uptake system of tadpole red blood cells : effect of endocrine-disrupting chemicals on cellular T3 response.2004

    • Author(s)
      Naoyuki Shimada
    • Journal Title

      Journal of Endocrinology 183・3

      Pages: 627-637

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Characteristics of 3,5,3'-tri-iodothyronine (T3)-uptake system of tadpole red blood cells : effect of endocrine-disrupting chemicals on cellular T3 response.2004

    • Author(s)
      Naoyuki Shimada
    • Journal Title

      Journal of Endocrinology 183・3

      Pages: 627-637

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 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)

    • Related Report
      2003 Annual Research Report
  • [Publications] 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)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kiyoshi Yamauchi: "Effect of coenzymes and thyroid hormones on the dual activities of Xenopus cytosolic thyroid-hormone-binding protein (xCTBP) with aldehyde dehydrogenase activity"European Journal of Biochemistry. 269・8. 2257-2264 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kiyoshi Yamauchi: "Competitive interactions of endocrine disrupting chemicals with thyroid hormone binding to Xenopus laevis transthyretin and thyroid hormone receptor"Clinical Chemistry and Laboratory Medicine. 40・12. 1250-1256 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 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)

    • Related Report
      2002 Annual Research Report
  • [Publications] 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)

    • Related Report
      2001 Annual Research Report
  • [Publications] 吉村 仁: "脱・環境ホルモン社会"三学出版. 155 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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