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Gene expression profiling to examine the thyroid hormone‐disrupting activity of hydroxylated polychlorinated biphenyls in metamorphosing amphibian tadpole
Author(s) -
Ishihara Akinori,
Makita Yu,
Yamauchi Kiyoshi
Publication year - 2011
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20390
Subject(s) - metamorphosis , thyroid , biology , hormone , xenopus , cytochrome p450 , amphibian , gene expression , medicine , gene , endocrinology , tadpole (physics) , gene expression profiling , thyroid hormone receptor , toad , metabolism , biochemistry , larva , ecology , physics , particle physics
Hydroxylated polychlorinated biphenyls are the metabolites produced from parent compounds by the drug‐metabolizing enzyme cytochrome P450. These compounds are suspected to disrupt postembryonic neural development in the brains of mammals including humans. We studied the effects of these compounds on thyroid hormone function in the brain by using metamorphosing tadpoles of the African clawed toad ( Xenopus laevis ) as a model for mammalian postembryonic development. The metamorphosis assay revealed that these compounds inhibit thyroid hormone‐induced metamorphosis. Genome‐wide gene expression analysis in the brain following short‐term exposure demonstrated that delayed metamorphosis could partially be caused by disruption of thyroid hormone‐induced gene expression. Furthermore, we associated the terms of functional ontology with the genes, whose expression was disrupted by these compounds. We suggest that the use of a genome‐wide analysis coupled with bioinformatics might provide an overview of the molecular mechanism underlying thyroid‐disrupting activities in vivo. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:303–311, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20390