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

1）。在体外培养的大鼠肝癌细胞（dRLH-84）生长周期中，细胞和细胞核对三碘甲腺原氨酸（T3）的摄取在G1早期逐渐增加，向G1晚期逐渐增加。细胞核T3受体水平也在G1期晚期增加。T3通过缩短dRLH-84细胞的G1晚期而促进其增殖。这些数据表明细胞在G1期晚期对T3敏感。另一方面，细胞和核甲状腺素（T4）的摄取在细胞周期中没有改变，表明T3和T4之间的细胞转运机制的差异。丁酸钠处理后，T3和T4之间的细胞和核摄取增加的差异也支持这种差异。2)拟甲状腺化合物SK&F L-94901（SKF）对肝脏发挥其活性，但对心脏或脑垂体不发挥其活性，并且可用于高脂血症的医学治疗而无肝外副作用。我们证明SKF在细胞激素水平上具有肝特异性拟甲状腺活性，而在核受体水平上则无此活性。这表明甲状腺激素的细胞转运在器官间是有差异的。3）。近年来的研究表明，细胞因子（IL-1 β、IL-6、TNF α）参与了病态甲状腺功能正常综合征（SES）的发病机制。我们发现，甲状腺激素的摄取和细胞因子的激素作用的改变，可以解释在SES的基础和TRH诱导的血清TSH水平下降，尽管血清T3水平低。数据还表明，细胞因子调节甲状腺激素的作用。4)利用非洲爪蟾卵母细胞表达系统，证明了在培养的大鼠垂体细胞（GH 3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).