11β-Hydroxysteroid dehydrogenases: Key modulators of glucocorticoid action in vivo

Yuri Kotelevtsev, Jonathan R. Seckl, John J. Mullins

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Intracellular interconversion of active 11-hydroxy glucocorticoids (cortisol, corticosterone) and inert 11 keto products (cortisone, 11- dehydrocorticosterone) by 11 β-hydroxysteroid dehydrogenase (11 β-HSD) enzymes has emerged as a new, potent mechanism of regulation of glucocorticoid action. 11β-hydroxysteroid dehydrogenase type 1 is a widespread, NADP(H)-dependent enzyme that shows bidirectional activity in tissue homogenates and microsomal preparations but functions predominantly as an 11β-reductase (regenerating active glucocorticoids) in intact cells. 11β-hydroxysteroid dehydrogenase type 2 is a much higher-affinity, NAD- dependent, exclusive 11β-dehydrogenase (glucocorticoid inactivating) enzyme that protects mineralocorticoid receptors in distal nephrons from nonselective activation by glucocorticoids in vivo. This review discusses the physiologic functions of 11β-HSDs and their potential diagnostic and therapeutic implications, as revealed by comparison of specific inhibition of 11β-HSD activity by pharmacologic substances and by genetic mutations (spontaneous in humans; targeted in mice).

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalCurrent Opinion in Endocrinology and Diabetes
Volume6
Issue number3
DOIs
Publication statusPublished - 1999
Externally publishedYes

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