The mechanism of cAMP-induced glucocorticoid receptor expression. Correlation to cellular glucocorticoid response

Y. Dong, M. Aronsson, J. A. Gustafsson, S. Okret

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

The mechanism of regulation of glucocorticoid receptor (GR) expression by cAMP was investigated in rat hepatoma cells (HTC). Incubation of HTC cells with the cAMP-inducing agent, forskolin, caused a significant increase in the levels of both [3H]dexamethasone binding capacity and GR mRNA by about 2- to 2.4-fold within 4 h. Incubation of HTC cells with the cAMP analogue, 8-bromo-cAMP, also increased the GR mRNA level to a similar degree in a concentration-dependent manner. The increase in GR mRNA did not require ongoing translation or transcription. Determination of GR mRNA stability in 8-bromo-cAMP-induced cells showed that the message had a half-life of approximately 10 h, which is about 2.5 times longer than the GR mRNA half-life in nontreated cells (t( 1/2 ) = 4 h). These results indicate that the increased steady state level of GR mRNA induced by cAMP analogue is, at least in part, caused by increased GR mRNA stability. In both forskolin-pretreated and nontreated HTC cells, dexamethasone caused an approximately 70% down-regulation of GR protein levels. However, since forskolin induced the GR level 2- to 2.4-fold, the relative amount of GR protein remaining in cells treated with both forskolin and dexamethasone was about 2- to 2.4-fold higher compared to cells treated with dexamethasone alone. This increased GR level correlated well with the increase in inducibility of two glucocorticoid regulated genes, the endogenous tyrosine aminotransferase and the stably integrated mouse mammary tumor virus. These data suggest that relatively small changes in GR levels are reflected in parallel changes in cellular response to glucocorticoid hormones. This also implicates a limiting nature of the GR protein in determining the biological response.

Original languageEnglish (US)
Pages (from-to)13679-13683
Number of pages5
JournalJournal of Biological Chemistry
Volume264
Issue number23
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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