Hexose 6-phosphate dehydrogenase (H6PD) and corticosteroid metabolism

Perrin C. White, Daniela Rogoff, D. Randy McMillan, Gareth G. Lavery

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations


Cortisone or (in rodents) 11-dehydrocorticosterone are reduced to cortisol or corticosterone, respectively, by the oxo-reductase activity of 11β-hydroxysteroid dehydrogenase type 1 (11-HSD1). This requires NADPH, generated by hexose-6-phosphate dehydrogenase (H6PD), a component of the pentose phosphate pathway. H6PD is located along with 11-HSD1 in the lumen of the endoplasmic reticulum (ER). Increasing or decreasing expression levels of H6PD in cultured cells has corresponding effects on the reductase activity of 11-HSD1. Mice carrying a targeted mutation in H6PD have drastically decreased 11-HSD1 oxo-reductase activity, but their 11-dehydrogenase activity is increased. They have many phenotypic features in common with mice carrying a mutation of 11-HSD1 itself. Polymorphisms in both H6PD and 11-HSD1 were originally identified in patients with apparent cortisone reductase deficiency (who have signs of hyperandrogenism and decreased urinary excretion of cortisol versus cortisone metabolites). However, these polymorphisms do not have detectable biochemical or physiologic effects when prospectively ascertained.

Original languageEnglish (US)
Pages (from-to)89-92
Number of pages4
JournalMolecular and Cellular Endocrinology
Issue numberSUPPL.
StatePublished - Feb 2007


  • 11β-Hydroxysteroid dehydrogenase
  • Corticosterone
  • Cortisol
  • Endoplasmic reticulum
  • Pentose phosphate pathway
  • Polycystic ovarian syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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