Regulation of Glucocorticoid Receptor Expression: Evidence for Transcriptional and Posttranslational Mechanisms
- 30 November 1988
- journal article
- research article
- Published by The Endocrine Society in Molecular Endocrinology
- Vol. 2 (12) , 1256-1264
- https://doi.org/10.1210/mend-2-12-1256
Abstract
The mechanism of ligand-induced (homologous) down-regulation of the glucocorticoid receptor (GR) has been studied. Dexamethasone caused a down-regulation of the levels of GR mRNA and protein both in hepatoma tissue culture cells and rat liver in vivo. The decrease in the level of rat liver GR mRNA was due to a reduced transcription rate of the GR gene, as assessed by nuclear run-on transcription experiments. The half-life of GR mRNA in hepatoma tissue culture cells was determined to be approximately 4.5 h and ws unaffected by dexamethasone. In addition to the transcriptional regulation of GR gene expression, a dexamethasone-dependent posttranslational modification in the rate of GR protein turnover was observed. In the absence of dexamethasone, GR protein half life was approximately 25 h whereas it decreased to approximately 11 h in the presence of hormone. Down-regulation of GR protein occurred with a 6- to 24-h delay as compared to the decline in GR mRNA. This is most likely due to the differences in half-lives of GR mRNA and protein, respectively. Our results suggest that autoregulation of GR by its cognate ligand is complex and occurs at both transcriptional and posttranslational levels.This publication has 37 references indexed in Scilit:
- Glucocorticoids regulate the glucocorticoid receptor in the AtT-20 cell.Journal of Biological Chemistry, 1981
- Glucocorticoid regulation of metallothionein-I mRNA synthesis in cultured mouse cells.Journal of Biological Chemistry, 1981
- Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose.Proceedings of the National Academy of Sciences, 1980
- Glucocorticoids and lymphocytes. II. Cell cycle-dependent changes in glucocorticoid receptor content.The Journal of Immunology, 1980
- Number and evolutionary conservation of α- and β-tubulin and cytoplasmic β- and γ-actin genes using specific cloned cDNA probesCell, 1980
- Isolation of biologically active ribonucleic acid from sources enriched in ribonucleaseBiochemistry, 1979
- ALTERATION IN BINDING OF DEXAMETHASONE TO GLUCOCORTICOID RECEPTORS IN REGENERATING RAT-LIVER AFTER PARTIAL-HEPATECTOMY1979
- Regulation of Translation of Ovalbumin Messenger RNA by Estrogens and Progesterone in Oviduct of Withdrawn ChicksEuropean Journal of Biochemistry, 1978
- Nuclei from Rat Liver: Isolation Method That Combines Purity with High YieldScience, 1966
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTJournal of Biological Chemistry, 1951