11β-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response

Abstract

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) interconverts inactive cortisone and active cortisol. Although bidirectional, in vivo it is believed to function as a reductase generating active glucocorticoid at a prereceptor level, enhancing glucocorticoid receptor activation. In this review, we discuss both the genetic and enzymatic characterization of 11beta-HSD1, as well as describing its role in physiology and pathology in a tissue-specific manner. The molecular basis of cortisone reductase deficiency, the putative "11beta-HSD1 knockout state" in humans, has been defined and is caused by intronic mutations in HSD11B1 that decrease gene transcription together with mutations in hexose-6-phosphate dehydrogenase, an endoluminal enzyme that provides reduced nicotinamide-adenine dinucleotide phosphate as cofactor to 11beta-HSD1 to permit reductase activity. We speculate that hexose-6-phosphate dehydrogenase activity and therefore reduced nicotinamide-adenine dinucleotide phosphate supply may be crucial in determining the directionality of 11beta-HSD1 activity. Therapeutic inhibition of 11beta-HSD1 reductase activity in patients with obesity and the metabolic syndrome, as well as in glaucoma and osteoporosis, remains an exciting prospect.

Evaluating the Fat Distribution in Idiopathic Intracranial Hypertension Using Dual-Energy X-ray Absorptiometry Scanning

“…Regional fat mass was analysed as described previously. 9–11 The precision of total fat mass measures in terms of coefficients of variation (CV) was less than 3%, and for regional fat analyses it was less than 5%. Regional fat data were expressed as a percentage of the total body fat.…”

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Switch of glycolysis to gluconeogenesis by dexamethasone for treatment of hepatocarcinoma

“…To maintain homeostasis within the body, GCs have to be precisely regulated in different tissues. Besides receptor-based regulation 23 , prereceptor metabolic regulation by dehydrogenase enzymes is also extremely important [24][25][26] . 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) intracellularly converts inert cortisone in human or dehydrocorticosterone in rodents into the active form, cortisol or corticosterone.…”