抄録
Polychrolinated biphenyls (PCBs) and dioxins (PCDD, PCDF, coplaner-PCB) are known as the environmental chemicals that may cause adverse effects of many organs including developing brain. WHO determined toxic index of dioxins as toxicity equivalent factor (TEF). We have previously reported that the magnitude of suppression of thyroid hormone (TH) receptor (TR)-mediated transcription by environmental chemicals does not always correlate to their TEFs. The magnitude of suppression by each congener was not correlated with the degree of dissociation. These findings have let us hypothesize that environmental chemicals may act on DNA binding domain of TR.In this study, we have investigated which domain of TR is responsible for such action of dioxins and PCBs. For this purpose, we performed transient cotransfection experiments using several chimeric proteins constructed by combination of glucocorticoid and TH receptors. EDCs suppressed the transactivation mediated by chimeric receptors that contain DNA binding domain (DBD) of TR. We also performed electrophoretic mobility shift assay (EMSA) with chimeric receptors and obtained that PCBs dissociated chimeric receptors containing DBD of TR from HRE. These results suggest that PCBs may affect TR-mediated transcription through DBD. [J Physiol Sci. 2007;57 Suppl:S171]
