Biology:11β-Hydroxysteroid dehydrogenase type 1

Short description: Mammalian protein found in Homo sapiens

Generic protein structure example

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.

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.

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.

Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and hence may explain why aspirin improves glycemic control in type 2 diabetes. Epigallocatechin gallate from green tea can also potently inhibit this enzyme; 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

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

External links

• Human HSD11B1 genome location and HSD11B1 gene details page in the UCSC Genome Browser.

Further reading

• "11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess". Endocrine Reviews 18 (1): 135–56. February 1997. doi:10.1210/edrv.18.1.0288. PMID 9034789. 
• "Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I enzyme and reduced co-factor NADPH". Endocrine Research 29 (4): 411–8. November 2003. doi:10.1081/ERC-120026947. PMID 14682470. 
• "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocrine Reviews 25 (5): 831–66. October 2004. doi:10.1210/er.2003-0031. PMID 15466942. 
• "Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity". Endocrine 29 (1): 101–8. February 2006. doi:10.1385/ENDO:29:1:101. PMID 16622297. 
• "The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization". The Journal of Biological Chemistry 266 (25): 16653–8. September 1991. doi:10.1016/S0021-9258(18)55351-5. PMID 1885595. 
• "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. June 1987. doi:10.1016/S0021-9258(18)47584-9. PMID 3034894. 
• "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. April 1995. doi:10.1016/0303-7207(95)03546-J. PMID 7545619. 
• "Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase". Nature Genetics 10 (4): 394–9. August 1995. doi:10.1038/ng0895-394. PMID 7670488. 
• "Immunohistochemical localization of type 1 11beta-hydroxysteroid dehydrogenase in human tissues". The Journal of Clinical Endocrinology and Metabolism 83 (4): 1325–35. April 1998. doi:10.1210/jcem.83.4.4706. PMID 9543163. 
• "Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL". Journal of Lipid Research 39 (4): 777–88. April 1998. doi:10.1016/S0022-2275(20)32566-9. PMID 9555943. 
• "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. October 1999. doi:10.1074/jbc.274.40.28762. PMID 10497248. 
• "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. October 1999. doi:10.1093/nar/27.20.3953. PMID 10497258. 
• "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. Jan 2000. doi:10.1101/gr.10.1.81. PMID 10645953. 
• "Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone". Bone 27 (3): 375–81. September 2000. doi:10.1016/S8756-3282(00)00344-6. PMID 10962348. 
• "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. April 2001. doi:10.1161/01.ATV.21.4.542. PMID 11304470. 
• "Effect of cellular differentiation on 11beta-hydroxysteroid dehydrogenase activity in the intestine". Steroids 67 (2): 119–26. February 2002. doi:10.1016/S0039-128X(01)00143-X. PMID 11755176. 
• "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. May 2002. doi:10.3892/ijmm.9.5.495. PMID 11956655. 
• "11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas". Journal of Investigative Medicine 50 (4): 288–92. July 2002. PMID 12109593. https://jim.bmj.com/lookup/pmidlookup?view=long&pmid=12109593.