Monden Tsuyoshi, Nakajima Yasuyo, Hashida Tetsu, Ishii Sumiyasu, Tomaru Takuya, Shibusawa Nobuyuki, Hashimoto Koshi, Satoh Teturou, Yamada Masanobu, Mori Masatomo, Kasai Kikuo
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Tochigi, Japan.
Endocr J. 2006 Apr;53(2):181-7. doi: 10.1507/endocrj.53.181.
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 TRalpha2 mRNA but not TRalpha1, beta1 or beta2 mRNA in the cell. The TRalpha1 and TRbeta1 mRNAs were detected only by RT-PCR method and TRbeta2 was not expressed. Incubation of T3 for 24 h decreased TRalpha1, TRalpha2 and TRbeta1 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.
甲状腺激素（T3）在包括小脑在内的中枢神经系统生长发育调节中的作用已得到充分证实。然而，甲状腺激素对源自小脑的恶性肿瘤的影响仍知之甚少。我们的分析主要集中在TR亚型的表达水平以及甲状腺激素对人髓母细胞瘤HTB - 185细胞的影响。Northern印迹分析显示该细胞中有TRα2 mRNA，但没有TRα1、β1或β2 mRNA。仅通过RT - PCR方法检测到TRα1和TRβ1 mRNA，且未表达TRβ2。用T3孵育24小时可降低TRα1、TRα2和TRβ1 mRNA水平。加入放线菌素D导致基础TR mRNA水平急剧增加，与对照组相比，T3处理组中各种TR亚型mRNA的下降速率加快，表明TR mRNA的稳定性受T3影响。用环己酰亚胺孵育也可阻断T3处理的HTB - 185细胞中TR mRNA水平的下降，这表明TR mRNA的下调需要新蛋白质的合成。我们的数据为HTB - 185细胞中T3下调TRs的表达提供了新证据，表明TR表达在RNA稳定性水平上受到T3的转录后调控。
