Expression of thyroid hormone receptor isoforms down-regulated by thyroid hormone in human medulloblastoma cells

The role of thyroid hormone (T3) in the regulation of growth and development of the central nervous system including the cerebellum has been well established. However, the effects of thyroid hormone on malignant tumors derived from the cerebellum remain poorly understood. Our analysis mainly focused on expression levels of TR isoforms and the effects of thyroid hormone in human medulloblastoma HTB-185 cells. Northern blot analysis revealed TR alpha 2 mRNA but not TR alpha 1, beta 1 or beta 2 mRNA in the cell. The TR alpha 1 and TR beta 1 mRNAs were detected only by RT-PCR method and TR beta 2 was not expressed. Incubation of T3 for 24 h decreased TR alpha 1, TR alpha 2 and TR beta I mRNA. Addition of actinomycin D caused an acute increase in the basal TR mRNA levels and the rate of decrease of all kinds of TR isoform mRNA was accelerated in the T3-treated groups compared to controls, indicating that the stability of TR mRNA was affected by T3. Incubation with cycloheximide also blocked a decrease in TR mRNA levels in the T3-treated HTB-185 cells suggesting that down-regulation of TR mRNA required the synthesis of new protein. Our data provide novel evidence for the expression of TRs down-regulated by T3 in HTB-185 cells, suggesting that TR expression is post-transcriptionally regulated by T3 at the level of RNA stability.