title: Establishment of transactivation assay systems using fish, amphibian, reptilian and human thyroid hormone receptors.
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.
authors.affiliation: Integrated Environmental Risk Research Section, Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Oka
authors.forename: Naoko
authors.initials: N
authors.lastname: Mitsui-Watanabe
authors.forename: Norihisa
authors.initials: N
authors.lastname: Tatarazako
authors.forename: Yuta
authors.initials: Y
authors.lastname: Onishi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Katsu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yatsu
authors.forename: Satomi
authors.initials: S
authors.lastname: Kohno
authors.forename: Minoru
authors.initials: M
authors.lastname: Takase
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ohta
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Aoki
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Guillette
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
mesh_terms: D000489:Alligators and Crocodiles / Q000378:metabolism; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D009990:Oryzias / Q000378:metabolism; D010802:Phylogeny; D011075:Polybrominated Biphenyls / Q000633:toxicity; D011898:Ranidae / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000378:metabolism; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D011075:Polybrominated Biphenyls; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; C020806:tetrabromobisphenol A; D013974:Thyroxine
keywords: alligator; amphibian; fish; human; thyroid hormone receptors; transactivation assay