Abstract
Normal cerebellar development requires several hormones. Recently, it has been a concern that environmental endocrine disrupters may interfere with hormonal functions in brain development. Polychlorinated biphenyls (PCBs) and hydroxylated PCB (OH-PCB) metabolites are widely distributed bioaccumulative environmental chemicals and have similar chemical structures to those of thyroid hormones (THs). Previously, we reported that THs are essential for the normal dendritic development of Purkinje cells, and low doses of two OH-PCBs, namely, 4-OH-2',3,3',4',5'-pentachlorobiphenyl (4'OH-PCB106) and 4-OH-2',3,3',4',5,5'-hexachlorobiphenyl (4'OH-PCB159), inhibited their TH-dependent development in mouse cerebellar cultures (Develop. Brain Res., 154: 259, 2005). Koibuchi et al. clarified in reporter gene assay that they interfere with TH-dependent gene expressions (JBC, 279:18195, 2004). On the other hand, 4-OH-2,2',3,4',5,5',6-heptachlorobiphenyl (4OH-PCB187), which was found to have the highest concentration among OH-PCB congeners in human cerebrospinal fluid (CSF) (Takasuga et al. Organo Halog Compounds 66:2529, 2004), did not inhibit TH activity in cerebellar cultures. However, it promoted an abnormal dendritic development of Purkinje cells and affects their survival rate. Furthermore, 4OH-PCB187 showed an inhibitory effect on synapse formation, which is essential for normal brain development. These results indicate that OH-PCB congeners may interfere with hormonal functions in brain development via several mechanisms depending on their chemical structure. [J Physiol Sci. 2007;57 Suppl:S44]
