| Cortisol metabolism in hypertension. | |
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MedLine Citation:
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PMID: 16980198 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Corticosteroids are critically involved in blood pressure regulation. Lack of adrenal steroids in Addison's disease causes life-threatening hypotension, whereas glucocorticoid excess in Cushing's syndrome invariably results in high blood pressure. At a pre-receptor level, glucocorticoid action is modulated by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). 11Beta-HSD1 activates cortisone to cortisol to facilitate glucocorticoid receptor (GR)-mediated action. By contrast, 11beta-HSD2 plays a pivotal role in aldosterone target tissues where it catalyses the opposite reaction (i.e. inactivation of cortisol to cortisone) to prevent activation of the mineralocorticoid receptor (MR) by cortisol. Mutations in the 11beta-HSD2 gene cause a rare form of inherited hypertension, the syndrome of apparent mineralocorticoid excess (AME), in which cortisol activates the MR resulting in severe hypertension and hypokalemia. Ingestion of competitive inhibitors of 11beta-HSD2 such as liquorice and carbenoxolone result in a similar but milder clinical phenotype. Epidemiological data suggests that polymorphic variability in the HSD11B2 gene determines salt sensitivity in the general population, which is a key predisposing factor to adult onset hypertension in some patients. Extrarenal sites of glucocorticoid action and metabolism that might impact on blood pressure include the vasculature and the central nervous system. Intriguingly, increased exposure to glucocorticoids during fetal life promotes high blood pressure in adulthood suggesting an early programming effect. Thus, metabolism and action in many peripheral tissues might contribute to the pathophysiology of human hypertension. |
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Authors:
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Fabian Hammer; Paul M Stewart |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Best practice & research. Clinical endocrinology & metabolism Volume: 20 ISSN: 1521-690X ISO Abbreviation: Best Pract. Res. Clin. Endocrinol. Metab. Publication Date: 2006 Sep |
Date Detail:
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Created Date: 2006-09-18 Completed Date: 2006-12-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101120682 Medline TA: Best Pract Res Clin Endocrinol Metab Country: England |
Other Details:
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Languages: eng Pagination: 337-53 Citation Subset: IM |
Affiliation:
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Division of Medical Sciences, University of Birmingham, Institute of Biomedical Research, Birmingham B15 2TT, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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11-beta-Hydroxysteroid Dehydrogenase Type 2
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antagonists & inhibitors ACTH Syndrome, Ectopic / diagnosis Antihypertensive Agents / therapeutic use Blood Pressure / drug effects Brain / drug effects Carbenoxolone / adverse effects Cardiovascular System / drug effects Fetal Growth Retardation / chemically induced Glucocorticoids / adverse effects Glycyrrhetinic Acid / analogs & derivatives Glycyrrhiza / adverse effects Humans Hydrocortisone / metabolism* Hypertension / metabolism* Mineralocorticoid Excess Syndrome, Apparent / diagnosis, drug therapy, genetics Models, Biological |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Glucocorticoids; 471-53-4/Glycyrrhetinic Acid; 50-23-7/Hydrocortisone; 5697-56-3/Carbenoxolone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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