|11-beta-hydroxysteroid dehydrogenase (NADP+)|
11-beta-hydroxysteroid dehydrogenase 1, dimer, Human
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
11β-Hydroxysteroid dehydrogenase (HSD-11β or 11β-HSD) is a family of enzymes that catalyze the conversion of inert 11 keto-products (cortisone) to active cortisol, or vice versa, thus regulating the access of glucocorticoids to the steroid receptors:
- 11β-hydroxysteroid + NADP+ ⇌ an 11-oxosteroid + NADPH + H+
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 11beta-hydroxysteroid:NADP+ 11-oxidoreductase. Other names in common use include corticosteroid 11β-dehydrogenase, β-hydroxysteroid dehydrogenase, 11β-hydroxy steroid dehydrogenase, corticosteroid 11-reductase, and dehydrogenase, 11β-hydroxy steroid. This enzyme participates in c21-steroid hormone metabolism and androgen and estrogen metabolism.
Cortisol, a glucocorticoid, binds the glucocorticoid receptor. However, because of its molecular similarity to aldosterone it is also capable of binding the mineralcorticoid receptor. Both aldosterone and cortisol have a similar affinity for the mineralocorticoid receptor; however, there is vastly more cortisol in circulation than aldosterone. To prevent over-stimulation of the mineralocorticoid receptor by cortisol, 11β-HSD converts the biologically active cortisol to the inactive cortisone, which can no longer bind to the mineralocorticoid receptor. 11β-HSD co-localizes with intracellular adrenal steroid receptors. Licorice, which contains glycyrrhetinic acid, or enoxolone, can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome.
|HSD11B1||NADPH-dependent||Highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system.||In these tissues, HSD11B1 reduces cortisone to the active hormone cortisol that activates glucocorticoid receptors.|
|HSD11B2||NAD+-dependent||Expressed in aldosterone-selective tissues, including kidneys, liver, lungs, colon, salivary glands, HSD2 neurons and placenta.||In these tissues, HSD11B2 oxidizes cortisol to cortisone and prevents illicit activation of the mineralocorticoid receptor.|
- Steroidogenic enzyme
- 11β-Hydroxysteroid dehydrogenase type 1
- 11β-Hydroxysteroid dehydrogenase type 2
- Cortisone reductase deficiency
- Seckl JR, Walker BR (April 2001). "Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action". Endocrinology. 142 (4): 1371–6. doi:10.1210/en.142.4.1371. PMID 11250914.
- Seckl JR (January 1997). "11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action?". Front Neuroendocrinol. 18 (1): 49–99. doi:10.1006/frne.1996.0143. PMID 9000459.
- Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP (2009). "Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis". The Journal of Clinical Endocrinology and Metabolism. 94 (8): 2692–2701. doi:10.1210/jc.2009-0370. PMID 19470627.
- Agarwal AK, Monder C, Eckstein B, White PC (1989). "Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase". J. Biol. Chem. 264 (32): 18939–43. PMID 2808402.
- Bush IE, Hunter SA, Meigs RA (1968). "Metabolism of 11-oxygenated steroids. Metabolism in vitro by preparations of liver". Biochem. J. 107 (2): 239–58. PMC . PMID 4384445.
- Lakshmi V, Monder C (1988). "Purification and characterization of the corticosteroid 11 beta-dehydrogenase component of the rat liver 11 beta-hydroxysteroid dehydrogenase complex". Endocrinology. 123 (5): 2390–8. doi:10.1210/endo-123-5-2390. PMID 3139396.
- Phillips DM, Lakshmi V, Monder C (1989). "Corticosteroid 11 beta-dehydrogenase in rat testis". Endocrinology. 125 (1): 209–16. doi:10.1210/endo-125-1-209. PMID 2661206.