Insulin and insulin-like growth factor I regulate a thyroid-specific nuclear protein that binds to the thyroglobulin promoter.
The mechanism responsible for the stimulation of thyroglobulin (Tg) gene expression by insulin and insulin-like growth factor I (IGF-I) in rat thyroid FRTL-5 cells has been investigated. Both insulin and IGF-I stimulate transcription from the Tg promoter in a transient transfection assay demonstrating that the promoter used contains the DNA signals necessary for insulin and IGF-I regulation. Promoter mutations that interfere with the binding of thyroid transcription factor 1 (TTF-1), TTF-2, and the ubiquitous transcription factor abolish the insulin/IGF-I response, indicating that the three factors may be involved in the observed transcriptional control. Protein-DNA binding studies did not reveal any effect of insulin/IGF-I on the ubiquitous transcription factor and the TTF-1 binding capacity. Instead, TTF-2 is absent in nuclear extracts from cells depleted of serum and insulin. Addition of insulin or IGF-I restores the TTF-2 concentration to normal levels and requires ongoing protein synthesis. The insulin effect was maximal at 24 h and at a concentration of 1 microgram/ml. The same effect was observed with a 10-fold lower concentration of IGF-I. These results suggest that insulin (probably through the IGF-I receptor) and IGF-I modulate the levels of TTF-2, which results in an increased expression of the Tg gene.
Santisteban
P
P
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Acebrón
A
A
Polycarpou-Schwarz
M
M
Di Lauro
R
R
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D013954:Thyroglobulin / Q000235:genetics*; D013961:Thyroid Gland / Q000737:chemistry*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection / Q000235:genetics
D004268:DNA-Binding Proteins; D007328:Insulin; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D013954:Thyroglobulin; D015500:Chloramphenicol O-Acetyltransferase