抄録
Thyroid hormone (TH)plays an important role in the developing brain. Deficiency of TH during perinatal period induces abnormal brain development known as cretinism. The neurological mutant mouse, staggerer (sg), harbors a deletion within the gene encoding retinoic acid receptor-related orphan nuclear receptor (ROR) α. This mouse shows hypothyroid-mice like phenotype. We previously showed that an evident alteration of cerebellar neurotrophin mRNA levels in sg mice using semi-quantitative RT-PCR and in situ hybridization. Moreover we showed that the sg type ROR (RORsg) was not effective in augmenting TR action through various TREs, although wild type RORα augmented TR-mediated transcription. Since RORα and TR are coexpressed in many neurons including the Purkinje cell, RORα may be generally required for a full function of TR action. In the present study, we investigated the mechanism of crosstalk between TR and RORα. We showed that DNA-binding domain and ligand-binding domain are responsible to this augmentation using a series of TR-mutants and reporter gene assays. This augmentation may not due to direct binding of ROR to TR. On the other hand, it has been speculated that polychlorinated biphenyl (PCB) may be involved in the increase in number of cretinism. We previously showed that as low as 10−10 M of PCB, suppressed TR-mediated transcription. Low dose of PCB suppressed TR-ROR-augmented transcription. These results indicated that the augmentation of TR by ROR is possibly due to a novel mechanism and ROR did not rescue the suppression of TR-mediated transcription by PCB. [J Physiol Sci. 2007;57 Suppl:S74]
