Sgk1 gene expression in kidney and its regulation by aldosterone: Spatio-temporal heterogeneity and quantitative analysis

Jianghui Hou, Helen J.L. Speirs, Jonathan R. Seckl, Roger W. Brown

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The serine-threonine kinase sgk1 was recently identified as a gene rapidly induced by mineralocorticoids, resulting in increased sodium transport in vitro. To carefully localize and quantify the renal sgk1 expression response to aldosterone, in situ hybridization was performed on kidneys of mice having aldosterone excess over a range of doses and durations. In control and adrenalectomized animals, the glomeruli and inner medullary collecting ducts were the major sites of sgk1 expression, which was maintained independent of aldosterone. Sgk1 upregulation induced by aldosterone excess exhibited spatio-temporal heterogeneity. Both acute (3-h) and chronic (6-d) aldosterone excess stimulated sgk1 expression in the distal nephron, i.e., from the distal convoluted tubules through to the outer medullary collecting ducts. Treatments for 6 d with low sodium diet (0.03% [I]) and aldosterone infusions (50 μg/kg per d [II], 150 μg/kg per d [III], and 750 μg/kg per d [IV]) generated elevation of circulating aldosterone. Across these treatments (I through IV), the circulating level correlated with the progressive induction of sgk1 expression, with highly stimulated tubules first appearing in cortex (I) and continuing downward (II) until there was a strong stimulation throughout outer medulla (III and IV). Interestingly, chronic but not acute aldosterone excess caused a slight increase of sgk1 expression in glomerulus (30 to 50%; P < 0.01) and a dramatic down-regulation in the initial portion of inner medulla, which could result from diminished interstitial osmolarity. Relative quantification (versus control) of sgk1 upregulation in individual tubules revealed: (1) a 1.8-fold increase of sgk1 mRNA at 3 h (150 μg/kg injection) and (2) a dose-dependence of chronic upregulation reaching a ceiling of eightfold elevation.

Original languageEnglish
Pages (from-to)1190-1198
Number of pages9
JournalJournal of the American Society of Nephrology
Volume13
Issue number5
DOIs
StatePublished - May 7 2002
Externally publishedYes

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