Clinical implications of glucocorticoid metabolism by 11beta-hydroxysteroid dehydrogenases in target tissues

M Quinkler, W Oelkers, S Diederich
2001 European Journal of Endocrinology  
11b-Hydroxysteroid dehydrogenases (11b-HSD) are microsomal enzymes that catalyze the conversion of active glucocorticoids (GC) to their inactive 11-dehydro products and vice versa. Two isoenzymes of 11b-HSD have been characterized and cloned in human tissues. The tissue-specific metabolism of GC by these enzymes is important for mineralocorticoid (MC) and GC receptor occupancy and seems to play a crucial role in the pathogenesis of diseases such as apparent MC excess syndrome, and may play
more » ... in hypertension, obesity and impaired hepatic glucose homeostasis. This article reviews the literature and examines the role and importance of 11b-HSD in humans. Enzyme kinetics In vitro bidirectional, in vivo mainly reductase Only dehydrogenase activity for endogenous steroids Low substrate affinity (K m -value in the mmol/l range) High substrate affinity (K m -value in nmol/l range) NADP/H preference NAD + preference High expression Liver, lung, gonads, pituitary, brain Kidney, colon, salivary glands, placenta Molecular biology Chromosome 1 Chromosome 16 Gene: 9 kb length, six exons Gene: 6.2 kb length, five exons Enzyme: 292 amino acids, 34 kDa Enzyme: 405 amino acids, 40 kDa Only 14% homology with 11b-HSD-type2 35% homology with 17b-HSD/KSR-type2 Function in vivo Alteration of intracellular GC concentration, organ-specific enhancement of GC effect Protection of MC receptor from cortisol KSR ketosteroid reductase.
doi:10.1530/eje.0.1440087 pmid:11182744 fatcat:kszlc5fohbcvznybsc27d45ske