Mechanism of glucocorticoid receptor down-regulation by glucocorticoids

S. Rosewicz, A. R. McDonald, B. A. Maddux, I. D. Goldfine, Roger Miesfeld, C. D. Logsdon

Research output: Contribution to journalArticle

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Abstract

The effect of glucocorticoids on the regulation of glucocorticoid receptor mRNA was studied in two different cell lines, human IM-9 lymphocytes and rat pancreatic acinar AR42J cells. Using a glucocorticoid receptor cDNA probe, glucocorticoid receptor mRNA was examined by Northern blot hybridization and quantitated by slot-blot hybridization. In IM-9 and AR42J cells, dexamethasone decreased steady-state glucocorticoid receptor mRNA levels to approximately 50% of control. This decrease occurred with a one-half time of 3 h for IM-9 cells and 6 h for AR42J cells. Dexamethasone was the most potent steroid tested with a one-half maximal effect occurring at 10 nM and a maximal effect occurring at 100 nM. Glucocorticoid receptor mRNA half-life and gene transcription were then studied to determine the mechanism of decreased mRNA levels. The glucocorticoid mRNA half-life was approximately 120 min in IM-9 cells and 240 min in AR42J cells; these rates were not affected by dexamethasone treatment. In contrast, the rate of glucocorticoid gene transcription as measured by run-on assays in IM-9 cells was decreased to 50 ± 6% of control by dexamethasone. These results indicate therefore that glucocorticoids regulate glucocorticoid receptor mRNA levels by influencing gene transcription.

Original languageEnglish (US)
Pages (from-to)2581-2584
Number of pages4
JournalJournal of Biological Chemistry
Volume263
Issue number6
StatePublished - 1988
Externally publishedYes

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Glucocorticoid Receptors
Glucocorticoids
Down-Regulation
Messenger RNA
Dexamethasone
Transcription
Genes
Half-Life
Lymphocytes
Acinar Cells
Northern Blotting
Rats
Assays
Complementary DNA
Steroids
Cells
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

Rosewicz, S., McDonald, A. R., Maddux, B. A., Goldfine, I. D., Miesfeld, R., & Logsdon, C. D. (1988). Mechanism of glucocorticoid receptor down-regulation by glucocorticoids. Journal of Biological Chemistry, 263(6), 2581-2584.

Mechanism of glucocorticoid receptor down-regulation by glucocorticoids. / Rosewicz, S.; McDonald, A. R.; Maddux, B. A.; Goldfine, I. D.; Miesfeld, Roger; Logsdon, C. D.

In: Journal of Biological Chemistry, Vol. 263, No. 6, 1988, p. 2581-2584.

Research output: Contribution to journalArticle

Rosewicz, S, McDonald, AR, Maddux, BA, Goldfine, ID, Miesfeld, R & Logsdon, CD 1988, 'Mechanism of glucocorticoid receptor down-regulation by glucocorticoids', Journal of Biological Chemistry, vol. 263, no. 6, pp. 2581-2584.
Rosewicz S, McDonald AR, Maddux BA, Goldfine ID, Miesfeld R, Logsdon CD. Mechanism of glucocorticoid receptor down-regulation by glucocorticoids. Journal of Biological Chemistry. 1988;263(6):2581-2584.
Rosewicz, S. ; McDonald, A. R. ; Maddux, B. A. ; Goldfine, I. D. ; Miesfeld, Roger ; Logsdon, C. D. / Mechanism of glucocorticoid receptor down-regulation by glucocorticoids. In: Journal of Biological Chemistry. 1988 ; Vol. 263, No. 6. pp. 2581-2584.
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