Stimulation of 11-beta-hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake.

ABSTRACT

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-beta-hydroxysteroid dehydrogenase type 2 (11betaHSD-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, 11betaHSD-2 protein by Western blot analysis, and localization of GR and 11betaHSD-2 by immunohistochemistry. NaCl restriction elevated plasma renin and aldosterone concentration, whereas corticosterone was unaltered. In distal colon, 11betaHSD-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 11betaHSD-2 mRNAs were not changed in kidney cortex and medulla, left cardiac ventricle, and aorta. Immunofluorescence labeling showed that GR and 11betaHSD-2 localization was mutually exclusive in kidney. In colon epithelium, nuclear staining for GR subsided as perinuclear 11betaHSD-2 immunoreactivity increased with NaCl restriction. As a functional correlate of increased 11betaHSD-2 expression in colon, the GR-stimulated sodium-hydrogen exchanger NHE-3 was lowered by NaCl restriction. Inhibition of 11betaHSD-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 11betaHSD-2 expression and tissue distribution in the distal colon, but not in the kidney.