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Establishment of transactivation assay systems using fish, amphibian, reptilian and human thyroid hormone receptors
Author(s) -
Oka Tomohiro,
MitsuiWatanabe Naoko,
Tatarazako Norihisa,
Onishi Yuta,
Katsu Yoshinao,
Miyagawa Shinichi,
Ogino Yukiko,
Yatsu Ryohei,
Kohno Satomi,
Takase Minoru,
Kawashima Yukio,
Ohta Yasuhiko,
Aoki Yasunobu,
Guillette Louis J.,
Iguchi Taisen
Publication year - 2013
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2825
Subject(s) - transactivation , thyroid hormone receptor , thyroid , medicine , hormone , biology , endocrinology , receptor , dio2 , triiodothyronine , deiodinase , biochemistry , gene expression , gene
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 (T 3 : 10 –11 M in TRα and 10 –10 M in TRβ) and thyroxine (T 4 : 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 T 3 and T 4 . 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 T 3 ‐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.