11β-Hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess

Perrin C. White, Tomoatsu Mune, Fraser M. Rogerson, Kathleen M. Kayes, Anil K. Agarwal

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Aldosterone, the most important mineralocorticoid, regulates electrolyte excretion and intravascular volume mainly through its effects on renal tubules and cortical collecting ducts, where it acts to increase sodium resorption from and potassium excretion into the urine. Excess secretion of aldosterone or other mineralocorticoids, or abnormal sensitivity to mineralocorticoids, may result in hypokalemia, suppressed plasma renin activity, and hypertension. The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11β-hydroxysteroid dehydrogenase (11β-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. Because mineralocorticoid receptors themselves have similar affinities for cortisol and aldosterone, it is hypothesized that the deficiency allows these receptors to be occupied by cortisol, which normally circulates at levels far higher than those of aldosterone. We cloned cDNA and genes encoding two isozymes of 11β-HSD. The liver (L) or type 1 isozyme has relatively low affinity for steroids, is expressed at high levels in the liver but poorly in the kidney, and is not defective in AME. The kidney (K) or type 2 isozyme had high steroid affinity and is expressed at high levels in the kidney and placenta. Mutations in the gene for the latter isozyme have been detected in all kindreds with AME. Moreover, the in vitro enzymatic activity conferred by each mutation is strongly correlated with the ratio of cortisol to cortisone metabolites in the urine [tetrahydrocortisone (THF) + allo-THF]/THE. This suggests that the biochemical phenotype of AME is largely determined by genotype.

Original languageEnglish (US)
Pages (from-to)25-29
Number of pages5
JournalPediatric Research
Volume41
Issue number1
DOIs
StatePublished - Jan 1997

    Fingerprint

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this