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      Mineralocorticoid effects in the kidney: correlation between alphaENaC, GILZ, and Sgk-1 mRNA expression and urinary excretion of Na+ and K+.

      Journal of the American Society of Nephrology : JASN

      Aldosterone, blood, pharmacology, Animals, Dexamethasone, Epithelial Sodium Channels, Gene Expression, drug effects, physiology, Glucocorticoids, Immediate-Early Proteins, Kidney Cortex, metabolism, Kidney Tubules, Collecting, Male, Nuclear Proteins, Potassium, urine, Protein-Serine-Threonine Kinases, genetics, RNA, Messenger, analysis, Rats, Rats, Wistar, Sodium, Sodium Channels, Transcription Factors

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          Abstract

          Aldosterone exerts its effects through interactions with two types of binding sites, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors. Although both receptors are known to be involved in the anti-natriuretic response to aldosterone, the mechanisms of signal transduction leading to modulation of electrolyte transport are not yet fully understood. This study measured the Na(+) and K(+) urinary excretion and the mRNA levels of three known aldosterone-induced transcripts, the serum and glucocorticoid-induced kinase (Sgk-1), the alpha subunit of the epithelial Na(+) channel (alphaENaC), and the glucocorticoid-induced-leucine-zipper protein (GILZ) in the whole kidney and in isolated cortical collecting tubules of adrenalectomized rats treated with low doses of aldosterone and/or dexamethasone. The resulting plasma concentrations of both steroids were close to 1 nmol/L. Aldosterone, given with or without dexamethasone, induced anti-natriuresis and kaliuresis, whereas dexamethasone alone did not. GILZ and alphaENaC transcripts were higher after treatment with either or both hormones, whereas the mRNA abundance of Sgk-1 was increased in the cortical collecting tubule by aldosterone but not by dexamethasone. We conclude the increased expression of Sgk-1 in the cortical collecting tubules is a primary event in the early antinatriuretic and kaliuretic responses to physiologic concentrations of aldosterone. Induction of alphaENaC and/or GILZ mRNAs may play a permissive role in the enhancement of the early and/or late responses; these effects may be necessary for a full response but do not by themselves promote early changes in urinary Na(+) and K(+) excretion.

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          12707381

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