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Cited by 517Hormonal Regulation and HypertensionAdrenal Hormones and DisordersRenin-Angiotensin System Studies

11β-Hydroxysteroid Dehydrogenase and the Syndrome of Apparent Mineralocorticoid Excess*

White, Perrin C., Mune, Tomoatsu, Agarwal, Anil K.·1997·Endocrine Reviews
DOI 10.1210/edrv.18.1.0288
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Abstract

Whereas aldosterone is normally a much stronger mineralocorticoid than cortisol in vivo, mineralocorticoid receptors have identical in vitro affinities for these hormones. The in vivo specificity of the receptors is, at least in part, the result of activity of 11-HSD, an enzyme located in most mineralocorticoid target tissues that converts cortisol to cortisone. Cortisone is not a ligand for the receptor, whereas aldosterone is not a substrate of the enzyme. The syndrome of AME is a rare form of juvenile hypertension in which 11-HSD is defective. This deficiency allows mineralocorticoid receptors to be occupied by cortisol, leading to hypertension, because plasma concentrations of cortisol are much higher than those of aldosterone. Licorice, which contains 11-HSD inhibitors, causes a similar syndrome. There are two known isozymes of 11-HSD. The liver or type I isozyme is expressed at high levels in the liver, has a relatively low affinity for steroids (micromolar Km), catalyzes both dehydrogenation and the reverse reductase reaction, and utilizes NADP+ or NADPH as cofactors. The kidney or type 2 isozyme is expressed at high levels in the kidney and placenta, has a high affinity (nanomolar Km) for steroids, catalyzes only dehydrogenation, and utilizes NAD+ as a cofactor. Mutations in the HSD11B2 (HSD11K) gene encoding the kidney isozyme of 11-HSD have been detected in all kindreds with AME studied thus far. This gene represents a candidate locus for the common, "essential" form of hypertension.

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Crossref · 10.1210/edrv.18.1.0288

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  • The placenta has abundant NADP+ favoring the oxidative action of 11βHSD1, so that in placenta both enzymes protect the fetus from high maternal concentrations of cortisol.

    “The placenta also has abundant NADP ϩ favoring the oxidative action of 11␤HSD1, so that in placenta both enzymes protect the fetus from high maternal concentrations of cortisol (570).”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [570]

  • Patients with AME have hypervolemic hypertension, salt retention, and hypokalemic alkalosis with suppressed plasma renin activity and without measurable serum mineralocorticoids due to recessive mutations of 11βHSD2.

    “Patients with AME have hypervolemic hypertension, salt retention, and hypokalemic alkalosis-the classic picture of hyperaldosteronism-but with suppressed plasma renin activity and without measurable serum mineralocorticoids due to recessive mutations of 11␤HSD2 (570).”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [570]

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Authors
White, P. C., Mune, T., & Agarwal, A. K.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Gifu University (JP)
ORCID
Venue
Endocrine Reviews
Publisher
The Endocrine Society
Published
1997-02-01
Volume
18
Issue
1
Pages
135-156
ISSN
  • 0163-769X (ISSN-L)
  • 1945-7189
DOI
10.1210/edrv.18.1.0288
OpenAlex
W1969503127
Cited by
517
References
4
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 11 · 2015: 10 · 2014: 20 · 2013: 26 · 2012: 16
FWCI
6.34
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrine Reviews (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk042169-12)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK42169)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords
11β-hydroxysteroid dehydrogenase, 11β-hydroxysteroid dehydrogenase type 2, apparent mineralocorticoid excess, mineralocorticoid receptor, cortisol, aldosterone, pediatric hypertension, licorice, 11β-hydroxysteroid dehydrogenase type 1, NAD+ cofactor, essential hypertension, genetic mutations
MeSH terms
ACTH Syndrome, Ectopic, Aldosterone, Glycyrrhiza, Humans, Hydroxysteroid Dehydrogenases, Hypertension, Isoenzymes, Mineralocorticoids, Mutation, Plants, Medicinal, Syndrome, Receptors, Mineralocorticoid, 11-beta-Hydroxysteroid Dehydrogenases

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