Glucocorticoid receptor concentration modulates glucocorticoid-regulated gene expression in rat pancreatic AR42J cells.
In this study we investigated the effects of altered intracellular glucocorticoid receptor (GR) concentrations on glucocorticoid-regulated gene expression in the rat pancreatic acinar cell line AR42J. Incubation of AR42J cells with dexamethasone results in a time-dependent transcriptional 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-regulated amylase and BR gene expression. In contrast, increasing the intracellular GR concentration 2-fold by preincubation with the phosphodiesterase inhibitor IBMX significantly enhances the glucocorticoid inhibition of BR gene expression whereas amylase mRNA concentrations remain unaltered. These data demonstrate that intracellular GR concentrations determine the sensitivity of glucocorticoid-regulated gene expression in rat pancreatic AR42J cells.
Kaiser
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Abteilung für Gastroenterologie, Klinikum Benjamin-Franklin, Freie Universität Berlin, Deutschland.
Stier
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Riecken
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Rosewicz
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000681:Amylases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D018004:Receptors, Bombesin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D006727:Hormone Antagonists; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D018004:Receptors, Bombesin; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D000681:Amylases; D015056:1-Methyl-3-isobutylxanthine