Saito T, Endo T, Nakazato M, Kogai T, Onaya T
Third Department of Internal Medicine, University of Yamanashi Medical School, Japan.
Endocrinology. 1997 Feb;138(2):602-6. doi: 10.1210/endo.138.2.4918.
Thyroid transcription factor 1 (TTF-1) is thought to play an important role in the expression of genes that encode thyroid-specific proteins such as thyroglobulin, thyroid peroxidase, and TSH-receptor. The role of TSH in the regulation of TTF-1 messenger RNA (mRNA) and protein abundance was investigated in rat thyroid FRTL-5 cells. Northern blot analysis revealed that TSH reduced TTF-1 mRNA abundance in a dose- and time-dependent manner. Immunoblot analysis with rabbit antibodies prepared against a recombinant fragment of TTF-1 expressed in bacteria showed that TSH also reduced the amount of TTF-1 protein in FRTL-5 cells. Whereas the effect of TSH on TTF-1 mRNA was apparent after 3 h, the effect on TTF-1 protein was not apparent until 12 h after TSH addition to the cells. Both TTF-1 mRNA and protein were significantly decreased after the addition of (Bu)2 cAMP or forskolin for 24 h, whereas they were not decreased by 12-O-tetradecanoyl-phorbol-13-acetate. These results indicate that TSH down-regulates TTF-1 expression in FRTL-5 cells via the cAMP pathway.
甲状腺转录因子1（TTF-1）被认为在编码甲状腺特异性蛋白（如甲状腺球蛋白、甲状腺过氧化物酶和促甲状腺激素受体）的基因表达中起重要作用。在大鼠甲状腺FRTL-5细胞中研究了促甲状腺激素（TSH）对TTF-1信使核糖核酸（mRNA）和蛋白质丰度的调节作用。Northern印迹分析显示，TSH以剂量和时间依赖性方式降低TTF-1 mRNA丰度。用针对在细菌中表达的TTF-1重组片段制备的兔抗体进行免疫印迹分析表明，TSH也降低了FRTL-5细胞中TTF-1蛋白的量。虽然TSH对TTF-1 mRNA的作用在3小时后明显，但对TTF-1蛋白的作用直到向细胞中添加TSH后12小时才明显。添加（Bu）2 cAMP或福斯高林24小时后，TTF-1 mRNA和蛋白均显著降低，而12-O-十四烷酰佛波醇-13-乙酸酯未使其降低。这些结果表明，TSH通过cAMP途径下调FRTL-5细胞中TTF-1的表达。
