PMID- 20861076
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20131121
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 299
IP  - 6
DP  - 2010 Dec
TI  - In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors 
      in rat kidney: differential effect of corticosteroids along the distal tubule.
PG  - F1473-85
LID - 10.1152/ajprenal.00437.2010 [doi]
AB  - 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 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) that 
      inactivates 11beta-hydroxy glucocorticoids. High expression levels of 11beta-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 
      11beta-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 11beta-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.
FAU - Ackermann, Daniel
AU  - Ackermann D
AD  - Unit of Anatomy, Department of Medicine, University of Fribourg, Fribourg, 
      Switzerland.
FAU - Gresko, Nikolay
AU  - Gresko N
FAU - Carrel, Monique
AU  - Carrel M
FAU - Loffing-Cueni, Dominique
AU  - Loffing-Cueni D
FAU - Habermehl, Daniel
AU  - Habermehl D
FAU - Gomez-Sanchez, Celso
AU  - Gomez-Sanchez C
FAU - Rossier, Bernard C
AU  - Rossier BC
FAU - Loffing, Johannes
AU  - Loffing J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100922
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Mineralocorticoid)
RN  - 0 (Sodium, Dietary)
RN  - 4964P6T9RB (Aldosterone)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism
MH  - Adrenalectomy
MH  - Aldosterone/metabolism/pharmacology
MH  - Animals
MH  - Antibody Specificity
MH  - Corticosterone/administration & dosage/metabolism/pharmacology
MH  - Kidney Tubules, Distal/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Nephrons/metabolism
MH  - *Protein Transport
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptors, Glucocorticoid/immunology/*metabolism
MH  - Receptors, Mineralocorticoid/immunology/*metabolism
MH  - Sodium, Dietary/administration & dosage/pharmacology
EDAT- 2010/09/24 06:00
MHDA- 2011/01/11 06:00
CRDT- 2010/09/24 06:00
PHST- 2010/09/24 06:00 [entrez]
PHST- 2010/09/24 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
AID - ajprenal.00437.2010 [pii]
AID - 10.1152/ajprenal.00437.2010 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2010 Dec;299(6):F1473-85. doi: 
      10.1152/ajprenal.00437.2010. Epub 2010 Sep 22.