Establishment of transactivation assay systems using fish, amphibian, reptilian and human thyroid hormone receptors

Authors

  • Tomohiro Oka,

    1. Integrated Environmental Risk Research Section, Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan
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  • Naoko Mitsui-Watanabe,

    1. Environmental Risk Research Center, Institute of Environmental Ecology, IDEA Consultants, Inc., Yaizu, Shizuoka, Japan
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  • Norihisa Tatarazako,

    1. Integrated Environmental Risk Research Section, Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan
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  • Yuta Onishi,

    1. Environmental Risk Research Center, Institute of Environmental Ecology, IDEA Consultants, Inc., Yaizu, Shizuoka, Japan
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  • Yoshinao Katsu,

    1. Department of Biological Sciences, Hokkaido University, Sapporo, Japan
    2. Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi, Japan
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  • Shinichi Miyagawa,

    1. Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi, Japan
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  • Yukiko Ogino,

    1. Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi, Japan
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  • Ryohei Yatsu,

    1. Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi, Japan
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  • Satomi Kohno,

    1. Department of Obstetrics and Gynecology & Marine Biomedicine and Environmental Science Center, Medical University of South Carolina and Hollings Marine Laboratory, Charleston, SC, USA
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  • Minoru Takase,

    1. Institute for Amphibian Biology, Graduate School of Science, Hiroshima University, Hiroshima, Japan
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  • Yukio Kawashima,

    1. Japan NUS Co. Ltd., Tokyo, Japan
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  • Yasuhiko Ohta,

    1. Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori, Japan
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  • Yasunobu Aoki,

    1. Integrated Environmental Risk Research Section, Research Center for Environmental Risk, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan
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  • Louis J. Guillette Jr,

    1. Department of Obstetrics and Gynecology & Marine Biomedicine and Environmental Science Center, Medical University of South Carolina and Hollings Marine Laboratory, Charleston, SC, USA
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  • Taisen Iguchi

    Corresponding author
    1. Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies, Okazaki, Aichi, Japan
    • Correspondence to: Taisen Iguchi, National Institute for Basic Biology, Okazaki, Japan. Email: taisen@nibb.ac.jp

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ABSTRACT

Thyroid hormones are essential for the regulation of a wide range of biological processes associated with normal development and metabolism in vertebrates. For the screening of chemicals with a potential thyroid hormone and anti-thyroid hormone activities, we have established transient transactivation assay systems using thyroid hormone receptors (TRα and TRβ) from three frog species (Xenopus laevis, Silurana tropicalis and Rana rugosa), a fish (Oryzias latipes), an alligator (Alligator mississippiensis) and a human (Homo sapiens). In all species examined, similar transcriptional activities were found for triiodothyronine (T3: 10–11 M in TRα and 10–10 M in TRβ) and thyroxine (T4: 10–9 M in TRα and 10–8 M in TRβ). Analogs of thyroid hormone (3,5,3′,-triiodothyroacetic acid and 3,3′,5,5′-tetraiodothyroacetic acid) exhibited weaker activity, requiring 10-fold higher concentrations for induction of activity when compared with T3 and T4. These results provide support for the usefulness of in vitro screening assay systems as part of an approach to test chemicals for potential thyroid hormone receptor activity. In addition, we observed that T3-stimulated transcriptional activity of the O. latipes TRα was inhibited by 10–5 M tetrabromobisphenol A (TBBPA). In contrast, TR antagonist activities on TRα were not encountered in other species, even with TBBPA concentrations at 10–5 M. In vitro transactivation assay systems using TRs from various species can be used for the screening of chemicals with thyroid-receptor agonist and antagonist activities. They also can be used for studies that examine evolutionary differences among species in the potency of TR activation. Copyright © 2012 John Wiley & Sons, Ltd.

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