Physiological roles of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase

Perrin C. White, Daniela Rogoff, D. Randy McMillan

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Purpose of Review: Inactive cortisone is converted to active cortisol by the reductase activity of 11β-hydroxysteroid dehydrogenase type 1, which can thus increase glucocorticoid effects in target tissues. This paper reviews the functional role(s) of 11β-hydroxysteroid dehydrogenase type 1 and examines factors influencing its activity. Recent Findings: In obese humans, 11β-hydroxysteroid dehydrogenase type 1 is relatively highly expressed in adipose tissue. In mice, overexpression of 11β-hydroxysteroid dehydrogenase type 1 in adipose or liver causes obesity or insulin resistance, respectively, whereas mice lacking 11β-hydroxysteroid dehydrogenase type 1 resist diet-induced obesity and are insulin-sensitive. Thus, 11β-hydroxysteroid dehydrogenase type 1 is a promising drug target for treating the metabolic syndrome and type 2 diabetes. Studies in vitro and in mutant mice demonstrate that the reductase activity of 11β-hydroxysteroid dehydrogenase type 1 depends on reduced nicotinamide adenine dinucleotide phosphate synthesized within the endoplasmic reticulum by hexose-6-phosphate dehydrogenase. Apparent cortisone reductase deficiency is characterized by androgen excess in women or children and decreased urinary excretion of cortisol metabolites. Although polymorphisms in the genes encoding 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase were initially implicated in this condition, subsequent reports have not confirmed this. Summary: Hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1 may play important roles in the pathogenesis of obesity and metabolic syndrome. Although the importance of polymorphisms in the corresponding genes remains uncertain, rare mutations have not been ruled out.

Original languageEnglish (US)
Pages (from-to)453-457
Number of pages5
JournalCurrent opinion in pediatrics
Volume20
Issue number4
DOIs
StatePublished - Aug 1 2008

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Keywords

  • Cortisol
  • Endoplasmic reticulum
  • Metabolic syndrome
  • Pentose phosphate pathway

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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