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

Rikke Nørregaard, Torben R Uhrenholt, Claus Bistrup, Ole Skøtt, Boye L Jensen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology - Renal Physiology
Vol/bind285
Udgave nummer2
Sider (fra-til)F348-F358
ISSN0363-6127
DOI
StatusUdgivet - 2003

Fingeraftryk

11-beta-Hydroxysteroid Dehydrogenase Type 2
Colon
Kidney
Glucocorticoid Receptors
Messenger RNA
Mineralocorticoids
Epithelium
Heart Ventricles
Kidney Medulla
Mineralocorticoid Receptors
Kidney Cortex
Ribonucleases
Aldosterone
Renin
Proteins

Citer dette

@article{53297cb0ba9a11dc9626000ea68e967b,
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.",
keywords = "11-beta-Hydroxysteroid Dehydrogenase Type 2, Aldosterone, Animals, Cardiovascular System, Colon, Corticosterone, Epithelial Cells, Gene Expression, Gene Expression Regulation, Enzymologic, Hydroxysteroid Dehydrogenases, Kidney Cortex, Male, Rats, Rats, Sprague-Dawley, Receptors, Glucocorticoid, Receptors, Mineralocorticoid, Renin, Sodium Chloride, Dietary, Journal Article, Research Support, Non-U.S. Gov't",
author = "Rikke N{\o}rregaard and Uhrenholt, {Torben R} and Claus Bistrup and Ole Sk{\o}tt and Jensen, {Boye L}",
year = "2003",
doi = "10.1152/ajprenal.00061.2003",
language = "English",
volume = "285",
pages = "F348--F358",
journal = "American Journal of Physiology: Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "2",

}

Stimulation of 11-beta hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake. / Nørregaard, Rikke; Uhrenholt, Torben R; Bistrup, Claus; Skøtt, Ole; Jensen, Boye L.

I: American Journal of Physiology - Renal Physiology, Bind 285, Nr. 2, 2003, s. F348-F358.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Stimulation of 11-beta hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake

AU - Nørregaard, Rikke

AU - Uhrenholt, Torben R

AU - Bistrup, Claus

AU - Skøtt, Ole

AU - Jensen, Boye L

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - 11-beta-Hydroxysteroid Dehydrogenase Type 2

KW - Aldosterone

KW - Animals

KW - Cardiovascular System

KW - Colon

KW - Corticosterone

KW - Epithelial Cells

KW - Gene Expression

KW - Gene Expression Regulation, Enzymologic

KW - Hydroxysteroid Dehydrogenases

KW - Kidney Cortex

KW - Male

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Glucocorticoid

KW - Receptors, Mineralocorticoid

KW - Renin

KW - Sodium Chloride, Dietary

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1152/ajprenal.00061.2003

DO - 10.1152/ajprenal.00061.2003

M3 - Journal article

C2 - 12842861

VL - 285

SP - F348-F358

JO - American Journal of Physiology: Renal Physiology

JF - American Journal of Physiology: Renal Physiology

SN - 1931-857X

IS - 2

ER -