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2001 Fiscal Year Final Research Report Summary

Effects of Endocrine Disrupting Chemicals on Thyroid Hormone Binding

Research Project

Project/Area Number 11839009
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research InstitutionShizuoka University

Principal Investigator

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

Project Period (FY) 1999 – 2001
KeywordsThyroid Hormone / Endocrine Disrupting Chemicals / Hormone Binding Proteins / Synthetic Xencestrogens / Alkylated Phenols / chichen / Amphibian
Research Abstract

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

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Kiyoshi Yamauchi: "Xenopus cytosclic thyroid hormone-binding protein (xCTBP) is aldehyde dehydrogenase catalizing the formation of retinoic acid"The Journal of Biological Chemistry. 274. 8460-8469 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kiyoshi Yamauchi: "Purification and characterization of thyroid-hormone-binding protein from masu salmon serum"European Journal of Biochemistry. 265. 944-949 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Porntip Prapunpoj: "Evolution of structure, ontogeny of gane expression and function of Xenopus laevis transthyretin"Americal Journal of Phyziology. 279. R2026-R2041 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kiyoshi Yamauchi: "Effect of diethylstilbestrol on thyroid-hormone-binding to amphibian transthyretin"General and Comparative Endocrinology. 119. 329-339 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kiyoshi Yamauchi: "Characterization of Xenopus cytosolic thyroid-hormone-binding protein(xCTBP)with aldehyde dehydrogenase activity"Chemico-Biological Interactions. 130-132. 309-321 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyoshi Yamauchi: "Purification and characterization of thyroid-hormone-binding protein from masu salmon serum"European Journal of Biochemistry. 265(3). 944-949 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Porntip Prapunpoj: "Evolution of structure, ontogeny of gene expression and function of Xenopus transthyretin"American Journal of Physiology. 279(6). R2026-R2041 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyoshi Yamauchi: "Effect of diethylstilbestrol on thyroid-hormone-binding to amphibian transthyretins"General and Comparative Endocrinology. 119(3). 329-339 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiyoshi Yamauchi: "Characterization of Xenopus cytosolic thyroid-hormone-binding protein (xCTBP) with aldehyde dehydrogenase activity"Chemico-Biological Interactions. 130-132. 309-321 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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