Document Detail


Insulin and insulin-like growth factor I regulate a thyroid-specific nuclear protein that binds to the thyroglobulin promoter.
MedLine Citation:
PMID:  1406708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
P Santisteban; A Acebrón; M Polycarpou-Schwarz; R Di Lauro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  6     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1992 Aug 
Date Detail:
Created Date:  1992-11-06     Completed Date:  1992-11-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1310-7     Citation Subset:  IM    
Affiliation:
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Cell Line
Chloramphenicol O-Acetyltransferase / genetics
DNA-Binding Proteins / biosynthesis,  metabolism*
Insulin / physiology*
Insulin-Like Growth Factor I / physiology*
Molecular Sequence Data
Nuclear Proteins / biosynthesis,  genetics,  metabolism*
Organ Specificity
Promoter Regions, Genetic*
Protein Binding
Rats
Thyroglobulin / genetics*
Thyroid Gland / chemistry*
Transcription Factors / genetics
Transcription, Genetic
Transfection / genetics
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/Transcription Factors; 0/thyroid nuclear factor 1; 11061-68-0/Insulin; 67763-96-6/Insulin-Like Growth Factor I; 9010-34-8/Thyroglobulin; EC 2.3.1.28/Chloramphenicol O-Acetyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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