Thyroid-stimulating hormone-induced down-regulation of thyroid transcription factor 1 in rat thyroid FRTL-5 cells.
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.
Saito
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Third Department of Internal Medicine, University of Yamanashi Medical School, Japan.
Endo
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Nakazato
M
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Kogai
T
T
Onaya
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T
D000818:Animals; D000918:Antibody Specificity; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007106:Immune Sera; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology
D007106:Immune Sera; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D005576:Colforsin; D003994:Bucladesine; D013972:Thyrotropin; D013755:Tetradecanoylphorbol Acetate