Evaluation of human thyroid hormone receptor-antagonist activity in 691 chemical compounds using a yeast two-hybrid assay with Saccharomyces cerevisiae Y190

Abstract

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.

Keywords

• yeast two-hybrid assay
• human thyroid receptor
• antagonist activity
• EDSP21