Functional studies of 11β-hydroxysteroid dehydrogenase

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

11β-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11-HSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the "short chain dehydrogenase" family. Using site-directed mutagenesis, it was demonstrated that two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Elimination of the amino terminus or the two glycosylation sites also destroys enzymatic activity. This may be due to actual disruption of enzymatic function or to effects on intracellular localization or stability of the enzyme. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11-HSD deficiency, did not reveal any mutations in the gene for this enzyme. There is substantial evidence for a second 11-HSD isozyme with distinct kinetic properties that is expressed in the renal distal tubule and possibly other sites of mineralocorticoid action. Apparent mineralocorticoid excess may involve this enzyme.

Original languageEnglish (US)
Pages (from-to)65-68
Number of pages4
JournalSteroids
Volume60
Issue number1
DOIs
StatePublished - 1995

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11-beta-Hydroxysteroid Dehydrogenases
Mineralocorticoids
Enzymes
Hydrocortisone
Apparent Mineralocorticoid Excess Syndrome
Distal Kidney Tubule
Rats
Enzyme Stability
Mineralocorticoid Receptors
Cortisone
Glycosylation
Site-Directed Mutagenesis
Aldosterone
Mutagenesis
Isoenzymes
Oxidoreductases
Complementary DNA
Clone Cells
Liver
Hypertension

Keywords

  • 11β-hydroxysteroid dehydrogenase
  • apparent mineralocorticoid excess
  • cortisol
  • cortisone
  • hypertension
  • mineralocorticoid receptor

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

Cite this

Functional studies of 11β-hydroxysteroid dehydrogenase. / White, Perrin C.; Mune, Tomoatsu; Agarwal, Anil K.

In: Steroids, Vol. 60, No. 1, 1995, p. 65-68.

Research output: Contribution to journalArticle

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