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PMID: 3016728 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Down-regulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 16 ·1986-08-00 ·Pages 5899-903

Okret S, Poellinger L, Dong Y, Gustafsson JA

Abstract

A cDNA clone for the rat glucocorticoid receptor (GR) was used to study mechanisms of GR mRNA regulation. Treatment of rat hepatoma culture cells with 0.5 microM dexamethasone caused a small, initial increase in the GR mRNA level after 6 hr as well as a 50% to 95% reduction of the GR mRNA level after 24 hr of incubation when studied by RNA blot hybridization. After 72 hr, the initial GR mRNA level was restored. The down-regulation of GR mRNA levels appears to be independent of protein synthesis, since it also was observed in the presence of cycloheximide. However, cycloheximide caused a 4-fold increase in intracellular levels of GR mRNA. Using an immunoprecipitation assay, we could demonstrate that the GR specifically interacts with a GR cDNA clone, which represents a 2.6-kilobase fragment of the 3' nontranslated region of the GR mRNA. Nuclease protection experiments indicate the presence of several internal GR-binding regions in the above fragment.

MeSH Terms
Animals Cell Line Cloning, Molecular DNA/metabolism DNA Restriction Enzymes Dexamethasone/pharmacology Homeostasis Liver Neoplasms, Experimental/metabolism Nucleic Acid Hybridization RNA, Messenger/genetics Rats Receptors, Glucocorticoid/genetics,metabolism Transcription, Genetic/drug effects
Chemicals
RNA, Messenger Receptors, Glucocorticoid Dexamethasone DNA DNA Restriction Enzymes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Okret S
Poellinger L
Dong Y
Gustafsson J A
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44 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.16.5899
Published
1986-08-00
Pages
5899-903
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC386404
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.83.16.5899 PMC Full Text View journal details
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