title: 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.
authors.affiliation: Department of Physiology and Pharmacology, University of Southern Denmark, Winsloewparken 21, 3 DK-5000 Odense C, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Nørregaard
authors.forename: Torben R
authors.initials: TR
authors.lastname: Uhrenholt
authors.forename: Claus
authors.initials: C
authors.lastname: Bistrup
authors.forename: Ole
authors.initials: O
authors.lastname: Skøtt
authors.forename: Boye L
authors.initials: BL
authors.lastname: Jensen
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000450:Aldosterone / Q000097:blood; D000818:Animals; D002319:Cardiovascular System / Q000201:enzymology; D003106:Colon / Q000201:enzymology*; D003345:Corticosterone / Q000097:blood; D004847:Epithelial Cells / Q000201:enzymology; D015870:Gene Expression / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D007672:Kidney Cortex / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
chemical_list: D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D012083:Renin; D003345:Corticosterone