11β-Hydroxysteroid dehydrogenase type 1

11β-Hydroxysteroid dehydrogenase type 1, also known as 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. It belongs to the family of short-chain dehydrogenases.

HSD11B1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHSD11B1, 11-DH, 11-beta-HSD1, CORTRD2, HDL, HSD11, HSD11B, HSD11L, SDR26C1, hydroxysteroid (11-beta) dehydrogenase 1, hydroxysteroid 11-beta dehydrogenase 1
External IDsOMIM: 600713 MGI: 103562 HomoloGene: 68471 GeneCards: HSD11B1
EC number1.1.1.146
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1q32.2Start209,686,178 bp[1]
End209,734,949 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

3290

15483

Ensembl

ENSG00000117594

ENSMUSG00000016194

UniProt

P28845

P50172

RefSeq (mRNA)

NM_181755
NM_001206741
NM_005525

NM_001044751
NM_008288

RefSeq (protein)

NP_001038216
NP_032314

Location (UCSC)Chr 1: 209.69 – 209.73 MbChr 1: 193.22 – 193.26 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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.[5]

Cortisol-cortisone equilibrium

Clinical significance

11β-HSD1 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.[6]

Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and hence may explain why aspirin improves glycemic control in type 2 diabetes.[7] Epigallocatechin gallate from green tea can also potently inhibit this enzyme;[8] green tea is a complex mixture of various phenolics with contents varying with production and processing, and some of the phenolics are known HDAC inhibitors that alter genetic expression. EGCG as usually consumed in green tea is poorly absorbed into the bloodstream. More research is needed to reach firm conclusions.

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000117594 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000016194 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: HSD11B1 hydroxysteroid (11-beta) dehydrogenase 1".
  6. Classen-Houben D, Schuster D, Da Cunha T, Odermatt A, Wolber G, Jordis U, Kueenburg B (February 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. S2CID 21938309.
  7. Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR (April 2012). "Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization". Diabetes. 61 (4): 790–6. doi:10.2337/db11-0931. PMC 3314355. PMID 22357964.
  8. 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. PMC 3880318. PMID 24404164.

Further reading


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