Document Detail

Glucocorticoid regulation of c-fos, c-jun and transcription factor AP-1 in the AtT-20 corticotrope cell.
MedLine Citation:
PMID:  7894465     Owner:  NLM     Status:  MEDLINE    
Glucocorticoids (GC) are potent repressors of both basal and corticotropin releasing factor (CRF) stimulated transcription of the proopiomelanocortin (POMC) gene in corticotrope cells of the anterior pituitary. Despite the finding of a novel, high affinity glucocorticoid receptor (GR) binding site within the proximal region of the POMC promoter, the mechanism by which GC inhibit POMC transcription is still uncertain. Recent studies have described mechanisms whereby GC inhibit transcription of other genes via a direct interaction with components of the transcription factor AP-1. Since it has been shown that CRF stimulates c-fos in AtT-20 corticotrope cells, and that c-fos over-expression elevates POMC transcription, the current study has investigated whether GC can repress c-fos and c-jun gene expression and AP-1 DNA binding activity in AtT-20 corticotrope cells. Acute treatment with doses of dexamethasone (DEX) that markedly inhibited nuclear POMC hnRNA had no effect on basal c-fos mRNA expression, but resulted in a transient down regulation of c-jun. In addition, acute DEX pretreatment significantly lowered CRF stimulation of POMC gene expression and attenuated the CRF stimulation of c-fos mRNA by 25%. Although DEX treatment of AtT-20 cells did not affect AP-1 DNA binding capacity of nuclear extracts, DEX pretreatment blunted the stimulation of AP-1 binding in response to CRF. In further studies, nuclear extracts from CRF-treated cells were coincubated with nuclear extracts from control or DEX treated cells. High levels of DEX treated extracts led to a relative repression of CRF-induced AP-1 binding, suggesting that ligand-activated GR may lower available AP-1 levels by direct protein: protein interaction. Finally, the composition of AP-1 in AtT-20 nuclear extracts was found to be heterogeneous, with the variation dependent upon hormonal treatment. These data suggest that in the corticotrope cell relatively high levels of activated GR may influence CRF-induced AP-1 DNA binding via transient genomic actions on basal c-jun and stimulated c-fos and/or via direct protein:protein interactions.
D J Autelitano
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  6     ISSN:  0953-8194     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-04-21     Completed Date:  1995-04-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  627-37     Citation Subset:  IM    
Molecular Physiology Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
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MeSH Terms
Base Sequence
Binding Sites
Corticotropin-Releasing Hormone / pharmacology
DNA / metabolism
Dexamethasone / pharmacology
Gene Expression Regulation / drug effects*
Genes, fos*
Genes, jun*
Glucocorticoids / pharmacology*
Nucleic Acid Hybridization
Pituitary Gland, Anterior / metabolism*
Pituitary Neoplasms
Pro-Opiomelanocortin / genetics*
RNA Probes
RNA, Messenger / metabolism
Receptors, Glucocorticoid / metabolism
Transcription Factor AP-1 / metabolism*
Tumor Cells, Cultured
Reg. No./Substance:
0/Glucocorticoids; 0/RNA Probes; 0/RNA, Messenger; 0/Receptors, Glucocorticoid; 0/Transcription Factor AP-1; 50-02-2/Dexamethasone; 66796-54-1/Pro-Opiomelanocortin; 9007-49-2/DNA; 9015-71-8/Corticotropin-Releasing Hormone

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

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