This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nguyen Dinh Cat, A. Articles by Jaisser, F. Search for Related Content PubMed PubMed Citation Articles by Nguyen Dinh Cat, A. Articles by Jaisser, F.

Conditional Transgenic Mice for Studying the Role of the Glucocorticoid Receptor in the Renal Collecting Duct

Institut National de la Santé et de la Recherche Médicale, Unité 772 (A.N.D.C., A.O.-P., D.G.-N., N.F., F.J.), College de France (A.N.D.C., A.O.-P., M.C., D.G.-N., N.F., F.J.), Université Paris Descartes (A.N.D.C., A.O.-P., F.T., M.C., D.G.-N., N.F., F.J.), Centre National de la Recherche Scientifique Unité Mixte de Recherche 7148 (F.T.), and Institut National de la Santé et de la Recherche Médicale, Unité 833 (M.C.), 75005 Paris, France

Address all correspondence and requests for reprints to: Dr. Frederic Jaisser, Institut Natíonal de la Santé et de la Recherche Medicalé Unité 772 College de France, 11 Place Marcelin Berthelot, 75005 Paris, France. E-mail: frederic.jaisser{at}college-de-france.fr.

The mineralocorticoid receptor (MR) is a major regulator of renal sodium reabsorption and body fluid homeostasis. However, little is known about glucocorticoid receptor (GR)-dependent renal effects. Glucocorticoids may activate both receptors, so it is difficult to distinguish between MR- and GR-mediated effects in vivo. To overcome this complexity, we used a transgenic mouse model allowing conditional GR overexpression (doxycycline inducible TetON system, Hoxb7 promoter) in the renal collecting duct (CD) to identify GR-regulated genes involved in sodium transport in the CD. In microdissected cortical CD, induction of GR expression led (after 2 d of doxycycline) to increased -epithelial sodium channel and glucocorticoid-induced leucine zipper and decreased abundance of with-no-lysine kinase 4 transcripts, without modification of Na,K-ATPase, serum- and glucocorticoid-kinase-1, or MR expression. No changes occurred in the upstream distal and connecting tubules [distal convoluted tubule (DCT), connecting tubule (CNT)]. Sodium excretion was unaltered, but the urinary aldosterone concentration was reduced, suggesting compensation of transitory extracellular volume expansion that subsequently disappeared. At steady state, i.e. after 15 d of doxycycline administration, transcript abundance remained altered in the CD, whereas mirror changes appeared in the DCT and CNT. Plasma aldosterone or glucocorticoids and blood pressure were all unaffected. These experiments show that: 1) GR, in addition to MR, controls epithelial sodium channel- and glucocorticoid-induced leucine zipper expression in vivo in the CD; 2) with-no-lysine kinase 4 is negatively controlled by GR; and 3) the DCT and CNT compensate for these alterations to maintain normal sodium reabsorption and blood pressure. These results suggest that enhanced GR expression may contribute to enhanced sodium retention in some pathological situations.

This article has been cited by other articles:

				M. A. Bailey, J. J. Mullins, and C. J. Kenyon Mineralocorticoid and Glucocorticoid Receptors Stimulate Epithelial Sodium Channel Activity in a Mouse Model of Cushing Syndrome Hypertension, October 1, 2009; 54(4): 890 - 896. [Abstract] [Full Text] [PDF]