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Third Department of Internal Medicine, University of Yamanashi Medical School, Tamaho, Yamanashi 409–38, Japan
Address all correspondence and requests for reprints to: Toshimasa Onaya, M.D., Third Department of Internal Medicine, University of Yamanashi Medical School, Tamaho, Yamanashi 409–38, Japan.
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.
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