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-hydroxysteroid
dehydrogenase isoforms in rat intestinal epithelia
Baker Medical Research Institute, Melbourne, Victoria 8008, Australia
To evaluate the potential roles that both
receptors and enzymes play in corticosteroid regulation of intestinal
function, we have determined glucocorticoid receptor (GR),
mineralocorticoid receptor (MR), and 11
-hydroxysteroid dehydrogenase
(11-HSD) expression in intestinal epithelial cells. GR and MR mRNA
and receptor binding were ubiquitously expressed in epithelial cells, with receptor levels higher in ileum and colon than jejunum and duodenum. RNase protection analysis showed that 11-HSD1 was not expressed in intestinal epithelial cells, and enzyme activity studies
detected no 11-reductase activity. 11-HSD2 mRNA and protein were
demonstrated in ileal and colonic epithelia; both MR and GR binding
increased when enzyme activity was inhibited with carbenoxolone. Duodenal and jejunal epithelial cells showed very little 11-HSD2 mRNA and undetectable 11-HSD2 protein; despite minor (<7%)
dehydrogenase activity in these cells, enzyme activity did not alter
binding of corticosterone to either MR or GR. These findings
demonstrate the ubiquitous but differential expression of MR and GR in
intestinal epithelia and that 11-HSD2 modulates corticosteroid
binding to both MR and GR in ileum and proximal and distal colon but
not in duodenum or jejunum.
glucocorticoid receptor; mineralocorticoid receptor
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