Modification of thyroid hormone action and molecular cloning of cDNA encoding cellular transporter of thyroid hormones.

1)。在培养的大鼠肝癌细胞(dRLH-84)的生长周期中，细胞和细胞核摄取三碘甲腺原氨酸(T3)在G1期早期最高，到G1期晚期逐渐增加。细胞核T_3受体水平也在G1期晚期升高。T3通过缩短dRLH84细胞的G1期晚期而促进该细胞的增殖。这些数据表明，在G1期晚期，细胞对T3敏感。另一方面，细胞和核的甲状腺激素(T4)摄取在细胞周期中没有改变，这表明T3和T4的细胞转运机制不同。这种差异也得到了丁酸钠治疗后T3和T4在细胞和核摄取增加方面的差异的支持。2)拟甲状腺化合物SK&F L-94901(SKF)作用于肝脏，而不作用于心脏和脑垂体，可用于治疗高脂血症，而无肝外不良反应。我们证明SKF是在激素的细胞转位水平上发挥肝脏特异性的类甲状腺激素活性，而不是在核受体水平上。这表明甲状腺激素的细胞转运在不同器官之间是不同的。3)。最近的研究表明，细胞因子(IL-1β、IL-6、肿瘤坏死因子α)参与了病态正常甲状腺综合征(SES)的发病机制。我们发现，细胞因子对甲状腺激素摄取和激素作用的改变，可能解释了基础水平和TRH诱导的血清TSH水平下降的原因，尽管自闭症患者血清T3水平较低。4)利用非洲爪哇卵母细胞表达系统，证明在培养的大鼠垂体细胞(GH3细胞)中存在编码甲状腺激素细胞转运蛋白的mRNA。

1). During cell growth cycle of cultured rat hepatoma cells (dRLH-84) , cellular and nuclear uptake of triiodothyronine (T3) was manimal in early G1 phase, was gradually incresed toward late G1 phase. Levels of the nuclear T3 receptor also increased in late G1 phase. T3 promoted the proliferation of dRLH-84 cells through shortening of late G1 phase in this cell line. These data indicate that cells are sensitive to T3 in late G1 phase. On the other hand, cellular and nuclear thyroxine (T4) uptake was not altered during cell cycle, indicating the difference in the cellular transport mechanism between T3 and T4. Such a difference was also supported by the differences between T3 and T4 in increases of cellular and nuclear uptake after sodium butyrate treatment. 2) The thyromimetic compound, SK&F L-94901 (SKF) , exerts its activity on liver but not on heart or pituitary gland and may be useful for medical treatment of hyperlipidemia without extrahepatic adverse effects. We proved that SKF exerts liver-specific thyromimetic activity at the level of cellular transoprt of hormones, but not at the level of nuclear receptor. This suggests that cellular transport of thyroid hormone deffers among organs. 3). Recent studies suggest the involvement of cytokines (IL-1 beta, IL-6, TNF alpha) in pathogenesis of sick euthyroid syndrome (SES) . We found that alteration of thyroid hormone uptake and hormone action by cytokines, may explain decrese in basal and TRH-induced serum TSH levels despite low serum T3 levels in SES.The data also suggest that cytokines modify thyroid hormone action. 4) By means of Xenopus oocyte expression system, we proved that mRNA encoding cellular transporter of thyroid hormone exists in cultured rat pituitary cells (GH3 cells).