Document Detail

In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule.
MedLine Citation:
PMID:  20861076     Owner:  NLM     Status:  MEDLINE    
Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the aldosterone-sensitive distal nephron (ASDN), which comprises the segment-specific cells of late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). We used MR- and GR-specific antibodies to study localization and regulation of MR and GR in kidneys of rats with altered plasma aldosterone and corticosterone levels. In control rats, MR and GR were found in cell nuclei of thick ascending limb (TAL), DCT, CNT, CD cells, and intercalated cells (IC). GR was also abundant in cell nuclei and the subapical compartment of proximal tubule (PT) cells. Dietary NaCl loading, which lowers plasma aldosterone, caused a selective removal of GR from cell nuclei of 11β-HSD2-positive ASDN. The nuclear localization of MR was unaffected. Adrenalectomy (ADX) resulted in removal of MR and GR from the cell nuclei of all epithelial cells. Aldosterone replacement rapidly relocated the receptors in the cell nuclei. In ASDN cells, low-dose corticosterone replacement caused nuclear localization of MR, but not of GR. The GR was redistributed to the nucleus only in PT, TAL, early DCT, and IC that express no or very little 11β-HSD2. In ASDN cells, nuclear GR localization was only achieved when corticosterone was replaced at high doses. Thus ligand-induced nuclear translocation of MR and GR are part of MR and GR regulation in the kidney and show remarkable segment- and cell type-specific characteristics. Differential regulation of MR and GR may alter the level of heterodimerization of the receptors and hence may contribute to the complexity of corticosteroid effects on ASDN function.
Daniel Ackermann; Nikolay Gresko; Monique Carrel; Dominique Loffing-Cueni; Daniel Habermehl; Celso Gomez-Sanchez; Bernard C Rossier; Johannes Loffing
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-22
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  299     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-08     Completed Date:  2011-01-10     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1473-85     Citation Subset:  IM    
Unit of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
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MeSH Terms
11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
Aldosterone / metabolism,  pharmacology
Antibody Specificity
Corticosterone / administration & dosage,  metabolism,  pharmacology
Kidney Tubules, Distal / drug effects*,  metabolism
Nephrons / metabolism
Protein Transport*
RNA, Messenger / metabolism
Receptors, Glucocorticoid / immunology,  metabolism*
Receptors, Mineralocorticoid / immunology,  metabolism*
Sodium, Dietary / administration & dosage,  pharmacology
Reg. No./Substance:
0/RNA, Messenger; 0/Receptors, Glucocorticoid; 0/Receptors, Mineralocorticoid; 0/Sodium, Dietary; 50-22-6/Corticosterone; 52-39-1/Aldosterone; EC Dehydrogenase Type 2

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