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-hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake
Department of Physiology and Pharmacology, University of Southern Denmark, Odense DK-5000, Denmark
Submitted 14 February 2003 ; accepted in final form 16 April 2003
Data suggest that mineralocorticoid selectivity is differentially regulated
in epithelial target tissues. We investigated whether the level of dietary
NaCl intake influenced the expression and tissue distribution of
11-
-hydroxysteroid dehydrogenase type 2 (11HSD-2), aldosterone
receptor (MR), and glucocorticoid receptor (GR) in rat colon, kidney, and
cardiovascular tissue. Rats were fed a diet with 0.01 or 3% NaCl for 10 days.
Messenger RNAs were analyzed with ribonuclease protection assay, 11HSD-2
protein by Western blot analysis, and localization of GR and 11HSD-2 by
immunohistochemistry. NaCl restriction elevated plasma renin and aldosterone
concentration, whereas corticosterone was unaltered. In distal colon,
11HSD-2 mRNA and protein were augmented significantly by low-NaCl intake
and immunolabeling was widely distributed in crypt and surface epithelium. The
MR mRNA level was decreased, whereas GR mRNA was unaltered in distal colon.
MR, GR, and 11HSD-2 mRNAs were not changed in kidney cortex and medulla,
left cardiac ventricle, and aorta. Immunofluorescence labeling showed that GR
and 11HSD-2 localization was mutually exclusive in kidney. In colon
epithelium, nuclear staining for GR subsided as perinuclear 11HSD-2
immunoreactivity increased with NaCl restriction. As a functional correlate of
increased 11HSD-2 expression in colon, the GR-stimulated sodium-hydrogen
exchanger NHE-3 was lowered by NaCl restriction. Inhibition of 11HSD-2
activity by carbenoxolone during NaCl restriction stimulated NHE-3 expression
in colon. Dexamethasone stimulated NHE-3 both in colon and kidney. These data
indicate that mineralocorticoid selectivity is physiologically regulated by
NaCl intake at the level of 11HSD-2 expression and tissue distribution
in the distal colon, but not in the kidney.
receptor; glucocorticoid; mineralocorticoid; aldosterone; corticosterone
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