Linked Life Data

15564339

Source:http://linkedlifedata.com/resource/pubmed/id/15564339

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-2-16
pubmed:abstractText
The mechanisms of receptor- and cell-specific effects of the adrenal corticosteroid hormones via mineralo- (MRs) and glucocorticoid receptors (GRs) are still poorly understood. Because the expression levels of two splice variants of the steroid receptor coactivator-1 (SRC-1) 1a and 1e, can differ significantly in certain cell populations, we tested the hypothesis that their relative abundance could determine cell- and receptor-specific effects of corticosteroid receptor-mediated transcription. In transient transfections, we demonstrate three novel types of SRC-1a- and SRC-1e-specific effects for corticosteroid receptors. One is promoter dependence: SRC-1e much more potently coactivated transcription from several multiple response element-containing promoters. Mammalian 1-hydrid studies indicated that this likely does not involve promoter-specific coactivator recruitment. Endogenous phenylethanolamine-N-methyltransferase mRNA induction via GRs was also differentially affected by the splice variants. Another type is receptor specificity: responses mediated by the N-terminal part of the MR, but not the GR, were augmented by SRC-1e at synergizing response elements. SRC fragment SRC(988-1240) by the MR but not the GR N-terminal fragment in a 1-hybrid assay. The last type, for GRs, is ligand dependence. Due to effects on partial agonism of RU486-activated GRs, different ratios of SRC-1a and 1e can lead to large differences in the extent of antagonism of RU486 on GR-mediated transcription. Furthermore, we show that SRC-1e but not SRC-1a mRNA expression was regulated in the pituitary by corticosterone. We conclude that the cellular differences in SRC-1a to SRC-1e ratio demonstrated in vivo might be involved in cell-specific responses to corticosteroids in a promoter- and ligand-dependent way.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
146
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1438-48
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15564339-Alternative Splicing, pubmed-meshheading:15564339-Animals, pubmed-meshheading:15564339-Blotting, Western, pubmed-meshheading:15564339-Cell Line, pubmed-meshheading:15564339-Cell Line, Tumor, pubmed-meshheading:15564339-Corticosterone, pubmed-meshheading:15564339-Genes, Reporter, pubmed-meshheading:15564339-Histone Acetyltransferases, pubmed-meshheading:15564339-Humans, pubmed-meshheading:15564339-In Situ Hybridization, pubmed-meshheading:15564339-Ligands, pubmed-meshheading:15564339-Models, Biological, pubmed-meshheading:15564339-Nuclear Receptor Coactivator 1, pubmed-meshheading:15564339-Plasmids, pubmed-meshheading:15564339-Polymerase Chain Reaction, pubmed-meshheading:15564339-Promoter Regions, Genetic, pubmed-meshheading:15564339-Protein Structure, Tertiary, pubmed-meshheading:15564339-RNA, Messenger, pubmed-meshheading:15564339-Rats, pubmed-meshheading:15564339-Rats, Wistar, pubmed-meshheading:15564339-Receptors, Steroid, pubmed-meshheading:15564339-Signal Transduction, pubmed-meshheading:15564339-Transcription, Genetic, pubmed-meshheading:15564339-Transcription Factors, pubmed-meshheading:15564339-Transfection
pubmed:year
2005
pubmed:articleTitle
Steroid receptor coactivator-1 splice variants differentially affect corticosteroid receptor signaling.
pubmed:affiliation
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research and Leiden University Medical Center, Leiden University, P.O. Box 9503, 2300 RA Leiden, The Netherlands. o.meijer@lacdr.leidenuniv.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't