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. It is encoded by the HSD11B1 gene.

HSD11B1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4P38, 1XU9, 2BEL, 2ILT, 2IRW, 2RBE, 3BYZ, 3BZU, 3CH6, 3CZR, 3D3E, 3D4N, 3D5Q, 3EY4, 3FCO, 3FRJ, 3H6K, 3HFG, 3OQ1, 3PDJ, 3QQP, 3TFQ, 4BB5, 4BB6, 4C7J, 4C7K, 4HFR, 4HX5, 4IJU, 4IJV, 4IJW, 4K1L, 4YYZ, 1XU7
Identifiers
Aliases	HSD11B1, 11-DH, 11-beta-HSD1, CORTRD2, HDL, HSD11, HSD11B, HSD11L, SDR26C1, hydroxysteroid (11-beta) dehydrogenase 1, hydroxysteroid 11-beta dehydrogenase 1
External IDs	OMIM: 600713; MGI: 103562; HomoloGene: 68471; GeneCards: HSD11B1; OMA:HSD11B1 - orthologs
EC number	1.1.1.146
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q32.2 Start 209,686,178 bp[1] End 209,734,949 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 H6 Start 192,903,942 bp[2] End 192,946,383 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in decidua right lobe of liver islet of Langerhans skin of thigh right ovary left ovary urethra right lung stromal cell of endometrium upper lobe of left lung Top expressed in left lobe of liver right lung lobe left lung umbilical cord gastrula decidua left lung lobe right kidney granulocyte white adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function 11-beta-hydroxysteroid dehydrogenase (NADP+) activity oxidoreductase activity 11-beta-hydroxysteroid dehydrogenase [NAD(P) activity] steroid binding Cellular component integral component of membrane endoplasmic reticulum membrane endoplasmic reticulum membrane Biological process glucocorticoid biosynthetic process lung development lipid metabolism steroid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3290 15483 Ensembl ENSG00000117594 ENSMUSG00000016194 UniProt P28845 P50172 RefSeq (mRNA) NM_181755 NM_001206741 NM_005525 NM_001044751 NM_008288 RefSeq (protein) NP_001193670 NP_005516 NP_861420 NP_001193670.1 NP_005516.1 NP_861420.1 NP_001038216 NP_032314 Location (UCSC) Chr 1: 209.69 – 209.73 Mb Chr 1: 192.9 – 192.95 Mb PubMed search [3] [4]
Wikidata
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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 liquorice root 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.^{[citation needed]}

Emestedastat is a compound being developed as a potential treatment of Alzheimer's disease and depression that acts by inhibiting 11β-HSD1.

See also

• Cortisone reductase deficiency
• 11β-hydroxysteroid dehydrogenase type 2