Thyroid hormone action in developing brain and its modulation by polyhalogenated aromatic hydrocarbons

Thyroid hormone (TH) plays a crucial role in brain development, particularly during perinatal period. Deficiency of TH during such period results in abnormal development known as cretinism in human. When animals are exposed to polyhalogenated aromatic hydrocarbons (PAHs) such as polychlorinated biphenyls (PCBs) and dioxins, they exhibit neurological abnormalities similar to those seen in cretinism animals. Therefore, part of abnormal brain development induced by PAH may be induced through disruption of TH system. Thus, we examined the effect of PAHs on TH receptor (TR)-mediated transcription. Using transient transfection-based reporter gene assay, TR-mediated transcription was suppressed by these compounds at various degrees. The suppression was induced by partial dissociation of TR from TH response element of DNA. These results indicate that abnormal brain development induced by PAHs is at least in part mediated through disruption of TR-mediated transcription.