Regulation of epithelial ion transport by aldosterone through changes in gene expression.
The year 2003 marks the 50th year since the unfolding of the chemical structures of both aldosterone and DNA. Since the recognition in the early 1960's that aldosterone and its cousin cortisol act through DNA binding proteins that alter gene transcription, research on these corticosteroid hormones and their receptors has attracted fervent attention, both for their importance in endocrine physiology, and as model systems for understanding gene regulation. Recently, aldosterone has emerged as arguably the single most important physiological regulator of extracellular fluid volume and blood pressure in mammals, and has been implicated in a variety of disease states in humans. Moreover, its principal receptor, the mineralocorticoid receptor is increasingly recognized as an important therapeutic target for the treatment of hypertension and congestive heart failure, as well as an important model system for understanding aspects of gene regulation. This increased insight into the functional and pathophysiologic importance of aldosterone has been accompanied by increased insight into its cellular and molecular mechanisms of action. Aldosterone acts in a variety of epithelial and non-epithelial tissues to influence extracellular fluid volume, blood pressure, salt appetite, and can under the appropriate conditions cause cardiac fibrosis. This review will address the current view of aldosterone's molecular mechanism of action in epithelia focusing primarily on the classical MR and on a particular MR target gene, SGK1.
Bhargava
Aditi
A
Departments of Medicine, Cellular & Molecular Pharmacology, University of California-San Francisco, Box 2140, N272C Genentach Hall, San Francisco, CA 94143-2140, USA.
Wang
Jian
J
Pearce
David
D
D000450:Aldosterone / Q000378:metabolism* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D003348:Cortisone / Q000378:metabolism / Q000627:therapeutic use; D004847:Epithelial Cells / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D018161:Receptors, Mineralocorticoid; D014158:Transcription, Genetic / Q000502:physiology
D000893:Anti-Inflammatory Agents; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003348:Cortisone