GLUCOCORTICOID RECEPTOR CONCENTRATION MODULATES GLUCOCORTICOID-REGULATED GENE-EXPRESSION IN RAT PANCREATIC AR42J CELLS

In this study we investigated the effects of altered intracellular glu cocorticoid receptor (GR) concentrations on glucocorticoid-regulated g ene expression in the rat pancreatic acinar cell line AR42J. Incubatio n of AR42J cells with dexamethasone results in a time-dependent transc riptional stimulation of amylase gene expression (about 5-fold) and a transcriptional inhibition of bombesin receptor (BR) gene expression. Decreasing the intracellular GR concentration to 50% by preincubation with RU 38486 results in a significant attenuation of dexamethasone-re gulated amylase and BR gene expression. In contrast, increasing the in tracellular GR concentration 2-fold by preincubation with the phosphod iesterase inhibitor IBMX significantly enhances the glucocorticoid inh ibition of BR gene expression whereas amylase mRNA concentrations rema in unaltered. These data demonstrate that intracellular GR concentrati ons determine the sensitivity of glucocorticoid-regulated gene express ion in rat pancreatic AR42J cells.