11β-hydroxysteroid dehydrogenase type 1
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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.
It is inhibited by carbenoxolone, a drug typically used in the treatment of peptic ulcers.
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]
See also
References
Further reading
- White PC, Mune T, Agarwal AK (1997). "11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess.". Endocr. Rev. 18 (1): 135–56. doi:10.1210/er.18.1.135. PMID 9034789.
- Agarwal AK (2004). "Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I enzyme and reduced co-factor NADPH.". Endocr. Res. 29 (4): 411–8. doi:10.1081/ERC-120026947. PMID 14682470.
- Tomlinson JW, Walker EA, Bujalska IJ et al. (2005). "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocr. Rev. 25 (5): 831–66. doi:10.1210/er.2003-0031. PMID 15466942.
- Odermatt A, Atanasov AG, Balazs Z et al. (2006). "Why is 11beta-hydroxysteroid dehydrogenase type 1 facing the endoplasmic reticulum lumen? Physiological relevance of the membrane topology of 11beta-HSD1". Mol. Cell. Endocrinol. 248 (1–2): 15–23. doi:10.1016/j.mce.2005.11.040. PMID 16412558.
- Wake DJ, Walker BR (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 et al. (1991). "The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization". J. Biol. Chem. 266 (25): 16653–8. PMID 1885595.
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- Whorwood CB, Mason JI, Ricketts ML et al. (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". Mol. Cell. Endocrinol. 110 (1–2): R7–12. doi:10.1016/0303-7207(95)03546-J. PMID 7545619.
- Mune T, Rogerson FM, Nikkilä H et al. (1995). "Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase". Nat. Genet. 10 (4): 394–9. doi:10.1038/ng0895-394. PMID 7670488.
- Ricketts ML, Verhaeg JM, Bujalska I et al. (1998). "Immunohistochemical localization of type 1 11beta-hydroxysteroid dehydrogenase in human tissues". J. Clin. Endocrinol. Metab. 83 (4): 1325–35. doi:10.1210/jc.83.4.1325. PMID 9543163.
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- Sriskanda V, Schwer B, Ho CK, Shuman S (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 Res. 27 (20): 3953–63. doi:10.1093/nar/27.20.3953. PMC 148661. PMID 10497258.
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- Reddy ST, Wadleigh DJ, Grijalva V et al. (2001). "Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids". Arterioscler. Thromb. Vasc. Biol. 21 (4): 542–7. doi:10.1161/01.ATV.21.4.542. PMID 11304470.
- Pácha J, Lisá V, Miksík I (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 et al. (2002). "Human adrenal cortex and aldosterone secreting adenomas express both 11beta-hydroxysteroid dehydrogenase type 1 and type 2 genes". Int. J. Mol. Med. 9 (5): 495–8. PMID 11956655.
- Mazzocchi G, Malendowicz LK, Aragona F et al. (2002). "11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas". J. Investig. Med. 50 (4): 288–92. doi:10.2310/6650.2002.33012. PMID 12109593.
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