| The role of 11β-hydroxysteroid dehydrogenase type 2 in human hypertension. | |
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MedLine Citation:
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PMID: 19909806 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cortisol and aldosterone have the same in vitro affinity for the mineralocorticoid receptor (MR), although in vivo only aldosterone acts as a physiologic agonist of the MR, despite circulating levels of cortisol in humans and corticosterone in rodents being three orders of magnitude higher than aldosterone levels. In mineralocorticoid target organs the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) inactivates 11-hydroxy steroids, to their inactive keto-forms, thus protecting the nonselective MR from activation by glucocorticoids. The gene is highly expressed in all sodium-transporting epithelia, particularly in the kidney and colon, but also in human placenta and vascular wall. Mutations in the HSD11B2 gene cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, compromised 11βHSD2 enzyme activity results in activation of the MR by cortisol, causing sodium retention, hypokalaemia, and salt-dependent hypertension. Whereas mutations or inhibition of 11βHSD2 by licorice have been clearly shown to produce a congenital or acquired syndrome of mineralocorticoid excess, the questions remaining are the extent to which subtle abnormalities in MR/11βHSD2 mechanisms may contribute to essential hypertension. Studies in patients with essential hypertension showed a prolonged half-life of cortisol and an increased ratio of urinary cortisol to cortisone metabolites, suggesting a deficient 11βHSD2 activity. These abnormalities may be genetically determined, as suggested by the association of a microsatellite flanking the HSD11B2 gene with hypertension in black patients with end-stage kidney disease and with salt sensitivity of blood pressure in healthy subjects. These findings indicate that variants of the HSD11B2 gene may contribute to the enhanced blood pressure response to salt and possibly to hypertension in humans. |
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Authors:
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Paolo Ferrari |
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Publication Detail:
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Type: Journal Article; Review Date: 2009-11-10 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1802 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-12-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1178-87 Citation Subset: IM |
Copyright Information:
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Copyright © 2009 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Nephrology, University of Western Australia, Alma Street, Perth, Western Australia 6160, Australia. paolo.ferrari@health.wa.gov.au |
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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genetics,
metabolism* Aldosterone / genetics, metabolism Animals Blood Pressure* Colon / metabolism Corticosterone / genetics, metabolism Humans Hydrocortisone / genetics, metabolism Hypertension / genetics, metabolism* Kidney / metabolism* Microsatellite Repeats / genetics Receptors, Mineralocorticoid / genetics, metabolism Rodentia Sodium / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Mineralocorticoid; 50-22-6/Corticosterone; 50-23-7/Hydrocortisone; 52-39-1/Aldosterone; 7440-23-5/Sodium; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2; EC 1.1.1.146/HSD11B2 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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