Document Detail

Growth hormone suppression of insulin-like growth factor binding protein-1 promoter activity.
MedLine Citation:
PMID:  10375014     Owner:  NLM     Status:  MEDLINE    
Hepatic transcription of insulin-like growth factor binding protein-1 (IGFBP-1) is rapidly downregulated by growth hormone (GH) which is also known to induce expression of c-fos and c-jun. Co-expression of c-fos or c-jun in rat hepatocytes, individually or together, suppresses IGFBP-1 promoter activity by approximately 60%. When hepatic nuclear extracts from sham-operated, hypophysectomized (hypox) and GH-treated hypox rats were analyzed by DNase-1 footprinting, differences in the protection pattern were identified in three regions of the IGFBP-1 promoter. F1 corresponding to - 660 to - 640 bp showed acute changes in response to GH administration. In additional regions, F2 and F3, representing - 758 to - 748 bp and - 477 to - 447 bp, respectively, differences were apparent between nuclear extracts from the hypox and sham-operated rats. When F1 and F2 were removed by deletion of the region from - 824 to - 557 bp, the GH response was lost but suppression by co-expression of c-fos and c-jun was preserved. A putative AP-1 binding site was present in the F3 footprint region, however removal of F3 did not affect the GH responsiveness. These data indicate that several distinct sequences, other than the putative AP-1 site are involved in mediating the GH effects on IGFBP-1 transcription.
X Lu; Z Shi; L J Murphy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  149     ISSN:  0303-7207     ISO Abbreviation:  Mol. Cell. Endocrinol.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-08-20     Completed Date:  1999-08-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  19-28     Citation Subset:  IM    
Department of Physiology, University of Manitoba, Winnipeg, Canada.
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MeSH Terms
Base Sequence
DNA Probes / genetics
Gene Expression / drug effects
Genes, fos
Genes, jun
Growth Hormone / pharmacology*
Insulin-Like Growth Factor Binding Protein 1 / genetics*
Liver / cytology,  metabolism
Promoter Regions, Genetic / drug effects*
Rats, Sprague-Dawley
Transcription Factor AP-1 / metabolism
Reg. No./Substance:
0/DNA Probes; 0/Insulin-Like Growth Factor Binding Protein 1; 0/Transcription Factor AP-1; 9002-72-6/Growth Hormone

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

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