Evaluation of human thyroid receptor-agonist activity in 796 chemical compounds using a yeast two-hybrid assay with <i>Saccharomyces cerevisiae</i> Y190

Abstract

The human thyroid receptor (hTR)-agonist activities of 796 compounds were evaluated using a yeast two-hybrid assay in this study. A total of 17 compounds exhibited agonist activity at tenfold the effective concentration (EC × 10 ) [0.0083 -7,500 nM]. Additionally, TRIAC, TETRAC, and GC-1, which exhibited 30 -200 times higher activities than T3 and T4, may cause thyroid-hormone receptors (TR) activity at extremely low concentrations in real environmental water. Moreover, 3-chloro-3',5,5'-triiodo-L-thyronine exhibited high TR-agonist activity for the first time. Chemicals with a structure equivalent to thyroid hormones exhibited TR-agonist activity regardless of the TR type. Information on hTR-agonist activity is important because previous studies, such as those involving EDSP21, have focused exclusively on rTR-agonist activity. Therefore, the knowledge gained from the present study will boost chemical regulation strategies benefiting human and wildlife.

Identification by Liquid Chromatography–Tandem Mass Spectrometry and Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry of the Contributor to the Thyroid Hormone Receptor Agonist Activity in Effluents from Sewage Treatment Plants

“…The EC ×10 value is close to the TRIAC concentrations detected in this study, and it was reported that the zebrafish genome shares 71% homology with humans . In addition, 10 nM T3 affected the ontogenetic expression of TH signaling genes in developing zebrafish, and the T3 concentration may be equivalent to 32 ng/L TRIAC because TRIAC has a 200 times higher hTR-agonist activity compared to T3 . These studies suggest that the environmental concentrations of TRIAC may affect the thyroid system of aquatic organisms.…”

“…In our previous study, we suggested that TRIAC, TETRAC, and GC-1 could strongly cause hTR-agonist activity . This study identified TRIAC in all the STP effluent samples, suggesting that it might closely relate to the hTR-agonist activity in the environment.…”

“…However, these contributors were unknown compounds in the case of the two Site1 samples mentioned above. They were probably excluded from not only the 13 compounds investigated here but also the list of compounds with rat TR-agonist activity published by the EDSP21 since all the latter were evaluated in our previous study …”

“…They were probably excluded from not only the 13 compounds investigated here but also the list of compounds with rat TR-agonist activity published by the EDSP21 30 since all the latter were evaluated in our previous study. 21 The Site4 sample showed a different trend. It did not exhibit hTR-agonist activity in the TR yeast cell assay, and TRIAC was not identified.…”

“…In our previous study, we suggested that TRIAC, TETRAC, and GC-1 could strongly cause hTR-agonist activity. 21 This study identified TRIAC in all the STP effluent samples, suggesting that it might closely relate to the hTR-agonist activity in the environment. Moreover, it was reported that an EC 80 of TRIAC is 6 nM (3726 ng/L) to zebrafish, 2 but EC ×10 was 0.008 nM to hTR (4.9 ng/L).…”