11β-hydroxysteroid dehydrogenase type 1

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Hydroxysteroid (11-beta) dehydrogenase 1
Protein HSD11B1 PDB 1xu7.png
PDB rendering based on 1xu7.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HSD11B1 ; 11-DH; 11-beta-HSD1; CORTRD2; HDL; HSD11; HSD11B; HSD11L; SDR26C1
External IDs OMIM600713 MGI103562 HomoloGene68471 IUPHAR: 2763 ChEMBL: 4235 GeneCards: HSD11B1 Gene
EC number 1.1.1.146
RNA expression pattern
PBB GE HSD11B1 205404 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3290 15483
Ensembl ENSG00000117594 ENSMUSG00000016194
UniProt P28845 P50172
RefSeq (mRNA) NM_001206741 NM_001044751
RefSeq (protein) NP_001193670 NP_001038216
Location (UCSC) Chr 1:
209.86 – 209.91 Mb
Chr 1:
193.22 – 193.26 Mb
PubMed search [1] [2]

11β-hydroxysteroid dehydrogenase type 1, or 'cortisone reductase' is an NADPH-dependent enzyme 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.

Function[edit]

The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Two transcript variants encoding the same protein have been found for this gene.[1]

Cortisol-cortisone equilibrium

Clinical significance[edit]

It is inhibited by carbenoxolone, a drug typically used in the treatment of peptic ulcers. Moreover, 18alpha-glycyrrhizic acid from the root of Glycyrrhiza glabra was discovered as an inhibitor [2] A study from 2014 found that Epigallocatechin gallate from Green tea can also potently inhibit this reaction,[3] which might partly explain the anti-stress properties of Green tea consumption.

See also[edit]

References[edit]

  1. ^ "Entrez Gene: HSD11B1 hydroxysteroid (11-beta) dehydrogenase 1". 
  2. ^ Classen-Houben D, Schuster D, Da Cunha T, Odermatt A, Wolber G, Jordis U et al. (Feb 2009). "Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid". The Journal of Steroid Biochemistry and Molecular Biology 113 (3-5): 248–52. doi:10.1016/j.jsbmb.2009.01.009. PMID 19429429. 
  3. ^ Hintzpeter J, Stapelfeld C, Loerz C, Martin HJ, Maser E (3 January 2014). "Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1". PloS One 9 (1): e84468. Bibcode:2014PLoSO...984468H. doi:10.1371/journal.pone.0084468. PMID 24404164. 


Further reading[edit]

  • White PC, Mune T, Agarwal AK (Feb 1997). "11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess". Endocrine Reviews 18 (1): 135–56. doi:10.1210/er.18.1.135. PMID 9034789. 
  • Agarwal AK (Nov 2003). "Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I enzyme and reduced co-factor NADPH". Endocrine Research 29 (4): 411–8. doi:10.1081/ERC-120026947. PMID 14682470. 
  • Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS et al. (Oct 2004). "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocrine Reviews 25 (5): 831–66. doi:10.1210/er.2003-0031. PMID 15466942. 
  • Odermatt A, Atanasov AG, Balazs Z, Schweizer RA, Nashev LG, Schuster D et al. (Mar 2006). "Why is 11beta-hydroxysteroid dehydrogenase type 1 facing the endoplasmic reticulum lumen? Physiological relevance of the membrane topology of 11beta-HSD1". Molecular and Cellular Endocrinology 248 (1-2): 15–23. doi:10.1016/j.mce.2005.11.040. PMID 16412558. 
  • Wake DJ, Walker BR (Feb 2006). "Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity". Endocrine 29 (1): 101–8. doi:10.1385/ENDO:29:1:101. PMID 16622297. 
  • Tannin GM, Agarwal AK, Monder C, New MI, White PC (Sep 1991). "The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization". The Journal of Biological Chemistry 266 (25): 16653–8. PMID 1885595. 
  • Graham DL, Oram JF (Jun 1987). "Identification and characterization of a high density lipoprotein-binding protein in cell membranes by ligand blotting". The Journal of Biological Chemistry 262 (16): 7439–42. PMID 3034894. 
  • Whorwood CB, Mason JI, Ricketts ML, Howie AJ, Stewart PM (Apr 1995). "Detection of human 11 beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 isoform to renal collecting ducts". Molecular and Cellular Endocrinology 110 (1-2): R7–12. doi:10.1016/0303-7207(95)03546-J. PMID 7545619. 
  • Mune T, Rogerson FM, Nikkilä H, Agarwal AK, White PC (Aug 1995). "Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase". Nature Genetics 10 (4): 394–9. doi:10.1038/ng0895-394. PMID 7670488. 
  • Ricketts ML, Verhaeg JM, Bujalska I, Howie AJ, Rainey WE, Stewart PM (Apr 1998). "Immunohistochemical localization of type 1 11beta-hydroxysteroid dehydrogenase in human tissues". The Journal of Clinical Endocrinology and Metabolism 83 (4): 1325–35. doi:10.1210/jc.83.4.1325. PMID 9543163. 
  • Calvo D, Gómez-Coronado D, Suárez Y, Lasunción MA, Vega MA (Apr 1998). "Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL". Journal of Lipid Research 39 (4): 777–88. PMID 9555943. 
  • Odermatt A, Arnold P, Stauffer A, Frey BM, Frey FJ (Oct 1999). "The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane". The Journal of Biological Chemistry 274 (40): 28762–70. doi:10.1074/jbc.274.40.28762. PMID 10497248. 
  • Sriskanda V, Schwer B, Ho CK, Shuman S (Oct 1999). "Mutational analysis of Escherichia coli DNA ligase identifies amino acids required for nick-ligation in vitro and for in vivo complementation of the growth of yeast cells deleted for CDC9 and LIG4". Nucleic Acids Research 27 (20): 3953–63. doi:10.1093/nar/27.20.3953. PMC 148661. PMID 10497258. 
  • Schutte BC, Bjork BC, Coppage KB, Malik MI, Gregory SG, Scott DJ et al. (Jan 2000). "A preliminary gene map for the Van der Woude syndrome critical region derived from 900 kb of genomic sequence at 1q32-q41". Genome Research 10 (1): 81–94. doi:10.1101/gr.10.1.81 (inactive 2015-02-15). PMC 310500. PMID 10645953. 
  • Cooper MS, Walker EA, Bland R, Fraser WD, Hewison M, Stewart PM (Sep 2000). "Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone". Bone 27 (3): 375–81. doi:10.1016/S8756-3282(00)00344-6. PMID 10962348. 
  • Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A et al. (Apr 2001). "Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids". Arteriosclerosis, Thrombosis, and Vascular Biology 21 (4): 542–7. doi:10.1161/01.ATV.21.4.542. PMID 11304470. 
  • Pácha J, Lisá V, Miksík I (Feb 2002). "Effect of cellular differentiation on 11beta-hydroxysteroid dehydrogenase activity in the intestine". Steroids 67 (2): 119–26. doi:10.1016/S0039-128X(01)00143-X. PMID 11755176. 
  • Albertin G, Tortorella C, Malendowicz LK, Aragona F, Neri G, Nussdorfer GG (May 2002). "Human adrenal cortex and aldosterone secreting adenomas express both 11beta-hydroxysteroid dehydrogenase type 1 and type 2 genes". International Journal of Molecular Medicine 9 (5): 495–8. doi:10.3892/ijmm.9.5.495. PMID 11956655. 
  • Mazzocchi G, Malendowicz LK, Aragona F, Tortorella C, Gottardo L, Nussdorfer GG (Jul 2002). "11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas". Journal of Investigative Medicine : The Official Publication of the American Federation for Clinical Research 50 (4): 288–92. doi:10.2310/6650.2002.33012. PMID 12109593.