Polychlorinated biphenyls suppress thyroid hormone-induced transactivation.
Polychlorinated biphenyls (PCBs) have been known as environmental endocrine disrupting chemical that causes various abnormalities in many organs including the central nervous system (CNS). To examine the effect of PCBs on thyroid hormone (T3)-mediated transcription, transfection-based reporter assays were performed. Surprisingly, as low as 10(-10)M of 4(OH)-2('),3,3('),4('),5(')-pentachloro biphenyl suppressed T3-induced transactivation by thyroid hormone receptor (TR) in various cell lines. Interestingly, among the cell lines that we tested, brain-derived cell line TE671 cells showed strong suppression by the PCB. The suppression of TR action by the PCB was not likely due to the ligand competition with T3. Various compounds of PCBs showed similar suppression. However, PCBs did not suppress glucocorticoid receptor-mediated transcription. Finally, we showed that PCBs suppress TR/coactivator (SRC-1) complex-mediated transactivation. In summary, our results suggest that very low dose of PCBs can potentially interfere with TR-mediated transactivation by influencing on TR/coactivator complex. As such, PCBs may disturb growth and development of TH target organ, particularly in the CNS.
Iwasaki
Toshiharu
T
Department of Physiology, Gunma University School of Medicine, Maebashi, Gunma, Japan.
Miyazaki
Wataru
W
Takeshita
Akira
A
Kuroda
Yoichiro
Y
Koibuchi
Noriyuki
N
D002460:Cell Line; D004785:Environmental Pollutants / Q000494:pharmacology*; D017930:Genes, Reporter; D051548:Histone Acetyltransferases; D006801:Humans; D056920:Nuclear Receptor Coactivator 1; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D014284:Triiodothyronine / Q000378:metabolism*
D004785:Environmental Pollutants; D037042:Thyroid Hormone Receptors beta; D015534:Trans-Activators; D014157:Transcription Factors; D014284:Triiodothyronine; D011078:Polychlorinated Biphenyls; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1