Evaluation of human thyroid hormone receptor-antagonist activity in 691 chemical compounds using a yeast two-hybrid assay with Saccharomyces cerevisiae Y190
Ryo Omagari,
Mayuko Yagishita,
Fujio Shiraishi,
Ryo Kamata,
Masanori Terasaki,
Takuya Kubo,
Daisuke Nakajima
Affiliations
Ryo Omagari
Health and Environmental Risk Division, National Institute for Environmental Studies, Japan; Corresponding author at: Health and Environmental Risk Division, National Institute for Environmental Studies (NIES), 16-2 Onogawa, Tsukuba-shi, Ibaraki-ken 305-8506 Japan
Mayuko Yagishita
Department of Life and Environmental Science, Prefectural University of Hiroshima, Japan
Fujio Shiraishi
Health and Environmental Risk Division, National Institute for Environmental Studies, Japan
Ryo Kamata
Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University, Japan
Masanori Terasaki
Graduate School of Arts and Sciences, Iwate University, Japan
Takuya Kubo
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Japan
Daisuke Nakajima
Health and Environmental Risk Division, National Institute for Environmental Studies, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Japan
The human thyroid receptor (hTR)-antagonist activities of 691 compounds were evaluated using a yeast two-hybrid assay with Saccharomyces cerevisiae Y190 introduced hTRα and coactivator. In parallel, those YTOX tests were conducted to evaluate whether those compounds affected either antagonism or toxicity. This is the first report that focuses on the hTR-antagonist activity of many chemical compounds suspected to be endocrine disruptor. In this study, 46 compounds exhibited antagonist activity at 50% of the maximum activity (IC × 50) within 11–9940 nM. In particular, 10,10-Oxybisphenoxarsine, triphenyltin fluoride, triphenyltin hydroxide, and chlorothalonil had strong hTR-antagonist activities. This knowledge gained from the present study will boost chemical regulation strategies for human and wildlife health.
