Hexose 6-phosphate dehydrogenase (H6PD) and corticosteroid metabolism

PC White, D Rogoff, DR McMillan, Gareth Lavery

    Research output: Contribution to journalArticle

    32 Citations (Scopus)


    Cortisone or (in rodents) 11-dehydrocorticosterone are reduced to cortisol or corticosterone, respectively, by the oxo-reductase activity of 11 beta-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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)89-92
    Number of pages4
    JournalMolecular and Cellular Endocrinology
    Publication statusPublished - 1 Jan 2007


    • polycystic ovarian syndrome
    • cortisol
    • corticosterone
    • 11 beta-hydroxysteroid dehydrogenase
    • endoplasmic reticulum
    • pentose phosphate pathway


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