Journal article

In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

  • Ackermann, Daniel Unit of Anatomy, Department of Medicine, University of Fribourg, Switzerland - Clinic for Nephrology and Hypertension, University Hospital of Bern, Switzerland
  • Gresko, Nikolay Institute for Anatomy, University of Zürich, Switzerland
  • Carrel, Monique Institute for Anatomy, University of Zürich, Switzerland
  • Loffing-Cueni, Dominique Institute for Anatomy, University of Zürich, Switzerland
  • Habermehl, Daniel German Cancer Research Center, Heidelberg, Germany
  • Gomez-Sanchez, Celso Department for Endocrinology, G. V. (Sonny) Montgomery Veterans Affairs Medical Center, University of Mississippi, Jackson, USA
  • Rossier, Bernard C. Department of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland
  • Loffing, Johannes Institute for Anatomy, University of Zürich, Switzerland
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  • American Journal of Physiology - Renal Physiology. - 2011, vol. 299, no. 6, p. F1473-F1485
English 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.
Faculté des sciences et de médecine
Département de Médecine
  • English
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