Genomes and Genes
Gene Symbol: Hsd11b1
Description: hydroxysteroid 11-beta dehydrogenase 1
Alias: corticosteroid 11-beta-dehydrogenase isozyme 1, 11-DH, 11-beta-HSD1, 11-beta-hydroxysteroid dehydrogenase 1, 11beta-HSD-1, 11beta-HSD1A, 11beta-hydroxysteroid dehydrogenase type 1, Corticosteroid 11-beta-dehydrogenase, isozyme 1 (11-DH) (11-beta-hydroxysteroid dehydrogenase 1) (11-beta-HSD1) (11beta-HSD1A)
- Balazs Z, Nashev L, Chandsawangbhuwana C, Baker M, Odermatt A. Hexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11beta-hydroxysteroid dehydrogenase 1. Mol Cell Endocrinol. 2009;301:117-22 pubmed publisher..In conclusion, cellular factors such as H6PDH can significantly modulate the effect of inhibitors and alternative 7-oxygenated substrates on intracellular glucocorticoid availability. ..
- Swali A, Walker E, Lavery G, Tomlinson J, Stewart P. 11beta-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets. Diabetologia. 2008;51:2003-11 pubmed publisher..mRNA expression of 11beta-HSD1 (also known as HSD11B1), glucocorticoid receptor and H6PDH (also known as H6PD) in human pancreas and murine islets was examined by real-..
- Dover A, Hadoke P, Macdonald L, Miller E, Newby D, Walker B. Intravascular glucocorticoid metabolism during inflammation and injury in mice. Endocrinology. 2007;148:166-72 pubmed..We conclude that increased generation of glucocorticoids by 11betaHSD1 in the murine vessel wall is unlikely to contribute to feedback regulation of inflammation. ..
- Hult M, Elleby B, Shafqat N, Svensson S, Rane A, Jornvall H, et al. Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. Cell Mol Life Sci. 2004;61:992-9 pubmed..These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7beta-OH cholesterol in humans, and point to a possible involvement of 11beta-HSD1 in atherosclerosis. ..
- Iqbal J, Macdonald L, Low L, Seckl J, Yau C, Walker B, et al. Contribution of endogenous glucocorticoids and their intravascular metabolism by 11Î²-HSDs to postangioplasty neointimal proliferation in mice. Endocrinology. 2012;153:5896-905 pubmed publisher..Reducing glucocorticoid action with 11Î²-HSD1 inhibitors that are being developed for type 2 diabetes appears not to risk enhanced neointimal proliferation. ..
- Yau J, McNair K, Noble J, BROWNSTEIN D, Hibberd C, Morton N, et al. Enhanced hippocampal long-term potentiation and spatial learning in aged 11beta-hydroxysteroid dehydrogenase type 1 knock-out mice. J Neurosci. 2007;27:10487-96 pubmed..These data suggest that 11beta-HSD1 deficiency enhances synaptic potentiation in the aged hippocampus and this may underlie the better maintenance of learning and memory with aging, which occurs in the absence of increased neurogenesis. ..
- Mitić T, Andrew R, Walker B, Hadoke P. 11?-Hydroxysteroid dehydrogenase type 1 contributes to the regulation of 7-oxysterol levels in the arterial wall through the inter-conversion of 7-ketocholesterol and 7?-hydroxycholesterol. Biochimie. 2013;95:548-55 pubmed publisher..This mechanism may be important in the cardioprotective effects of 11?-HSD1 inhibitors. ..
- Dzyakanchuk A, Balazs Z, Nashev L, Amrein K, Odermatt A. 11beta-Hydroxysteroid dehydrogenase 1 reductase activity is dependent on a high ratio of NADPH/NADP(+) and is stimulated by extracellular glucose. Mol Cell Endocrinol. 2009;301:137-41 pubmed publisher..Our results suggest significant cell type-specific differences in ER-luminal NADPH generation that might allow a fine-tuned regulation of glucocorticoid action. ..
- Luo M, Thieringer R, Springer M, Wright S, Hermanowski Vosatka A, Plump A, et al. 11?-HSD1 inhibition reduces atherosclerosis in mice by altering proinflammatory gene expression in the vasculature. Physiol Genomics. 2013;45:47-57 pubmed publisher..Taken together, our data suggest 11?-HSD1 inhibition regulates proinflammatory gene expression in atherosclerotic tissues of ApoE-/- mice, and this effect may contribute to the attenuation of atherosclerosis in these animals. ..
- Thompson A, Han V, Yang K. Differential expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 mRNA and glucocorticoid receptor protein during mouse embryonic development. J Steroid Biochem Mol Biol. 2004;88:367-75 pubmed
- Alberts P, Engblom L, Edling N, Forsgren M, Klingström G, Larsson C, et al. Selective inhibition of 11beta-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice. Diabetologia. 2002;45:1528-32 pubmed..These results suggest that a selective inhibitor of human 11beta-hydroxysteroid dehydrogenase type 1 can become a new approach for lowering blood glucose concentrations in Type II diabetes. ..
- Garcia R, Search D, Lupisella J, Ostrowski J, Guan B, Chen J, et al. 11?-hydroxysteroid dehydrogenase type 1 gene knockout attenuates atherosclerosis and in vivo foam cell formation in hyperlipidemic apoE?/? mice. PLoS ONE. 2013;8:e53192 pubmed publisher..The diminished cytokine response to oxidized LDL stimulation is consistent with the reduction in TLR expression and suggests involvement of 11?HSD1 in modulating binding of pro-atherogenic TLR ligands. ..
- Morgan S, Sherlock M, Gathercole L, Lavery G, Lenaghan C, Bujalska I, et al. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. Diabetes. 2009;58:2506-15 pubmed publisher..Selective 11beta-HSD1 inhibition decreases pSer(307) IRS1, increases pThr(308) Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action. ..
- Justesen J, Mosekilde L, Holmes M, Stenderup K, Gasser J, Mullins J, et al. Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation. Endocrinology. 2004;145:1916-25 pubmed..The clinical relevance of this observation remains to be determined. ..
- Staab C, Stegk J, Haenisch S, Neiss E, Köbsch K, Ebert B, et al. Analysis of alternative promoter usage in expression of HSD11B1 including the development of a transcript-specific quantitative real-time PCR method. Chem Biol Interact. 2011;191:104-12 pubmed publisherOverexpression of the microsomal enzyme 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1, human gene HSD11B1 or SDR26C1) associates with the metabolic syndrome as well as some inflammatory diseases...
- De Sousa Peixoto R, Turban S, Battle J, Chapman K, Seckl J, Morton N. Preadipocyte 11beta-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in vivo. Endocrinology. 2008;149:1861-8 pubmed publisher..The results suggest that 11beta-HSD1 reductase activity is augmented in mouse mesenteric preadipocytes where it promotes preadipocyte differentiation and contributes to visceral fat accumulation in obesity. ..
- Nixon M, Wake D, Livingstone D, Stimson R, Esteves C, Seckl J, et al. Salicylate downregulates 11?-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. 2012;61:790-6 pubmed publisher..Reduced intra-adipose glucocorticoid regeneration by 11?-HSD1 is a novel mechanism that contributes to the metabolic efficacy of salicylates. ..
- Small G, Hadoke P, Sharif I, Dover A, Armour D, Kenyon C, et al. Preventing local regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 enhances angiogenesis. Proc Natl Acad Sci U S A. 2005;102:12165-70 pubmed
- Morton N, Ramage L, Seckl J. Down-regulation of adipose 11beta-hydroxysteroid dehydrogenase type 1 by high-fat feeding in mice: a potential adaptive mechanism counteracting metabolic disease. Endocrinology. 2004;145:2707-12 pubmed..Adaptive down-regulation of adipose 11beta-HSD-1 in response to chronic HF represents a novel mechanism that may counteract metabolic disease. ..
- Michailidou Z, Turban S, Miller E, Zou X, Schrader J, Ratcliffe P, et al. Increased angiogenesis protects against adipose hypoxia and fibrosis in metabolic disease-resistant 11?-hydroxysteroid dehydrogenase type 1 (HSD1)-deficient mice. J Biol Chem. 2012;287:4188-97 pubmed publisher..Improved adipose angiogenesis and reduced fibrosis provide a novel mechanism whereby suppression of intracellular glucocorticoid regeneration promotes safer fat expansion with weight gain. ..
- Yau J, Noble J, Kenyon C, Hibberd C, Kotelevtsev Y, Mullins J, et al. Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments. Proc Natl Acad Sci U S A. 2001;98:4716-21 pubmed..The data emphasize the crucial importance of local enzymes in determining intracellular glucocorticoid activity. Selective 11beta-HSD-1 inhibitors may protect against hippocampal function decline with age. ..
- Masuzaki H, Paterson J, Shinyama H, Morton N, Mullins J, Seckl J, et al. A transgenic model of visceral obesity and the metabolic syndrome. Science. 2001;294:2166-70 pubmed..Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1)...
- McSweeney S, Hadoke P, Kozak A, Small G, Khaled H, Walker B, et al. Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11betaHSD1-deficient mice post-MI. Cardiovasc Res. 2010;88:159-67 pubmed publisher..Mature infarcts show less thinning and cardiac function is improved relative to wild-type mice, suggesting that 11?HSD1 may be a novel therapeutic target after MI. ..
- Morton N, Paterson J, Masuzaki H, Holmes M, Staels B, Fievet C, et al. Novel adipose tissue-mediated resistance to diet-induced visceral obesity in 11 beta-hydroxysteroid dehydrogenase type 1-deficient mice. Diabetes. 2004;53:931-8 pubmed..These data provide the first in vivo evidence that adipose 11 beta-HSD-1 deficiency beneficially alters adipose tissue distribution and function, complementing the reported effects of hepatic 11 beta-HSD-1 deficiency or inhibition. ..
- Speirs H, Seckl J, Brown R. Ontogeny of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development. J Endocrinol. 2004;181:105-16 pubmed
- Zhang T, Ding X, Daynes R. The expression of 11 beta-hydroxysteroid dehydrogenase type I by lymphocytes provides a novel means for intracrine regulation of glucocorticoid activities. J Immunol. 2005;174:879-89 pubmed..Thus, the presence of 11beta-HSD1 provides an additional means to facilitate GCS influences over lymphocyte activities, uncoupled from the plasma concentration of GCS. ..
- Paterson J, Holmes M, Kenyon C, Carter R, Mullins J, Seckl J. Liver-selective transgene rescue of hypothalamic-pituitary-adrenal axis dysfunction in 11beta-hydroxysteroid dehydrogenase type 1-deficient mice. Endocrinology. 2007;148:961-6 pubmed..Therefore, hepatic glucocorticoid metabolism influences basal as well as stress-associated functions of the HPA axis. ..
- Sooy K, Webster S, Noble J, Binnie M, Walker B, Seckl J, et al. Partial deficiency or short-term inhibition of 11beta-hydroxysteroid dehydrogenase type 1 improves cognitive function in aging mice. J Neurosci. 2010;30:13867-72 pubmed publisher..These data support the use of selective 11?-HSD1 inhibitors in the treatment of age-related cognitive impairments. ..
- Kotelevtsev Y, Holmes M, Burchell A, Houston P, Schmoll D, Jamieson P, et al. 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc Natl Acad Sci U S A. 1997;94:14924-9 pubmed..The 11beta-HSD-1 -/- mice were found to resist hyperglycamia provoked by obesity or stress. Attenuation of hepatic 11beta-HSD-1 may provide a novel approach to the regulation of gluconeogenesis. ..
- Lee J, Gao Z, Ye J. Regulation of 11?-HSD1 expression during adipose tissue expansion by hypoxia through different activities of NF-?B and HIF-1?. Am J Physiol Endocrinol Metab. 2013;304:E1035-41 pubmed publisher..This study suggests that NF-?B may mediate the inflammatory cytokine signal to upregulate 11?-HSD1 expression. ..
- Ortsäter H, Alberts P, Warpman U, Engblom L, Abrahmsen L, Bergsten P. Regulation of 11beta-hydroxysteroid dehydrogenase type 1 and glucose-stimulated insulin secretion in pancreatic islets of Langerhans. Diabetes Metab Res Rev. 2005;21:359-66 pubmed..Increased levels of 11beta-HSD1 were associated with impaired GSIS. ..
- Wamil M, Andrew R, Chapman K, Street J, Morton N, Seckl J. 7-oxysterols modulate glucocorticoid activity in adipocytes through competition for 11beta-hydroxysteroid dehydrogenase type. Endocrinology. 2008;149:5909-18 pubmed publisher..Thus, the activity and reaction direction of adipose 11beta-HSD1 is altered under conditions of oxysterol excess, and could impact upon the pathophysiology of obesity and its complications. ..
- Morton N, Holmes M, Fievet C, Staels B, Tailleux A, Mullins J, et al. Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11beta-hydroxysteroid dehydrogenase type 1 null mice. J Biol Chem. 2001;276:41293-300 pubmed..Further, 11beta-HSD-1(-/-) mice have improved glucose tolerance. These data suggest that 11beta-HSD-1 deficiency produces an improved lipid profile, hepatic insulin sensitization, and a potentially atheroprotective phenotype. ..
- Hadoke P, Christy C, Kotelevtsev Y, Williams B, Kenyon C, Seckl J, et al. Endothelial cell dysfunction in mice after transgenic knockout of type 2, but not type 1, 11beta-hydroxysteroid dehydrogenase. Circulation. 2001;104:2832-7 pubmed..This appears to be independent of renal sodium retention and may contribute to hypertension in 11betaHSD2 deficiency. ..
- Hardy R, Doig C, Hussain Z, O LEARY M, Morgan S, Pearson M, et al. 11?-Hydroxysteroid dehydrogenase type 1 within muscle protects against the adverse effects of local inflammation. J Pathol. 2016;240:472-483 pubmed publisher..2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. ..
- Doig C, Bashir J, Zielinska A, Cooper M, Stewart P, Lavery G. TNF?-mediated Hsd11b1 binding of NF-?B p65 is associated with suppression of 11?-HSD1 in muscle. J Endocrinol. 2014;220:389-96 pubmed publisher..This upregulation was mediated by the P2 promoter of the Hsd11b1 gene and was dependent on the NF-?B signalling pathway...
- Liu X, Tan X, Xia M, Wu C, Song J, Wu J, et al. Loss of 11Î²HSD1 enhances glycolysis, facilitates intrahepatic metastasis, and indicates poor prognosis in hepatocellular carcinoma. Oncotarget. 2016;7:2038-53 pubmed publisher..In conclusion, 11Î²HSD1 inhibits the intrahepatic metastasis of HCC via restriction of tumor glycolysis activity and may serve as a prognostic biomarker for patients. ..
- Verma M, Kipari T, Zhang Z, Man T, Forster T, Homer N, et al. 11Î²-hydroxysteroid dehydrogenase-1 deficiency alters brain energy metabolism in acute systemic inflammation. Brain Behav Immun. 2018;69:223-234 pubmed publisher..Inflammation was induced in 11Î²-HSD1 deficient (Hsd11b1Del/Del) and C57BL/6 control mice by intraperitoneal injection of lipopolysaccharide (LPS)...
- Mitić T, Shave S, Semjonous N, McNae I, Cobice D, Lavery G, et al. 11?-Hydroxysteroid dehydrogenase type 1 contributes to the balance between 7-keto- and 7-hydroxy-oxysterols in vivo. Biochem Pharmacol. 2013;86:146-53 pubmed publisher..In health, 7-oxysterols are unlikely to regulate glucocorticoid metabolism. However, in hyperlipidaemia, 7-oxysterols may inhibit glucocorticoid metabolism and modulate signaling through corticosteroid receptors. ..
- Stulnig T, Oppermann U, Steffensen K, Schuster G, Gustafsson J. Liver X receptors downregulate 11beta-hydroxysteroid dehydrogenase type 1 expression and activity. Diabetes. 2002;51:2426-33 pubmed..In conclusion, LXR ligands could mediate beneficial metabolic effects in insulin resistance syndromes including type 2 diabetes by interfering with peripheral glucocorticoid activation. ..
- Terao M, Itoi S, Murota H, Katayama I. Expression profiles of cortisol-inactivating enzyme, 11?-hydroxysteroid dehydrogenase-2, in human epidermal tumors and its role in keratinocyte proliferation. Exp Dermatol. 2013;22:98-101 pubmed publisher..Assessing 11?-HSD1 and 11?-HSD2 expression could be a useful tool for diagnosing and characterizing skin tumors...
- Harno E, Cottrell E, Yu A, Deschoolmeester J, Gutierrez P, Denn M, et al. 11?-Hydroxysteroid dehydrogenase type 1 (11?-HSD1) inhibitors still improve metabolic phenotype in male 11?-HSD1 knockout mice suggesting off-target mechanisms. Endocrinology. 2013;154:4580-93 pubmed publisher..These data challenge the concept that inhibition of 11?-HSD1 is likely to produce a "step-change" treatment for diabetes and/or obesity. ..
- Yau J, Wheelan N, Noble J, Walker B, Webster S, Kenyon C, et al. Intrahippocampal glucocorticoids generated by 11Î²-HSD1 affect memory in aged mice. Neurobiol Aging. 2015;36:334-43 pubmed publisher..These data provide the first in vivo evidence that dynamic increases in hippocampal 11Î²-HSD1 regenerated CORT levels during learning and retrieval play a key role in age- and stress-associated impairments of spatial memory. ..
- Terao M, Itoi S, Matsumura S, Yang L, Murota H, Katayama I. Local Glucocorticoid Activation by 11?-Hydroxysteroid Dehydrogenase 1 in Keratinocytes: The Role in Hapten-Induced Dermatitis. Am J Pathol. 2016;186:1499-510 pubmed publisher..of 11?-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific 11?-HSD1 knockout (K5-Hsd11b1-KO) mice and analyzed the inflammatory response in models of hapten-induced contact irritant dermatitis...
- Chapagain A, Caton P, Kieswich J, Andrikopoulos P, Nayuni N, Long J, et al. Elevated hepatic 11?-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia. Proc Natl Acad Sci U S A. 2014;111:3817-22 pubmed publisher..Specific 11?HSD1 inhibitors potentially represent a novel therapeutic approach for management of insulin resistance in patients with CKD. ..
- Liu J, Kong X, Wang L, Qi H, Di W, Zhang X, et al. Essential roles of 11?-HSD1 in regulating brown adipocyte function. J Mol Endocrinol. 2013;50:103-13 pubmed publisher..2733. Our results indicate that 11?-HSD1 acts as a vital regulator that controls the expression of genes related to brown fat function and as such may become a potential target in preventing obesity. ..
- Kim J, Temple K, Jones S, Meredith K, Basko J, Brady M. Differential modulation of 3T3-L1 adipogenesis mediated by 11beta-hydroxysteroid dehydrogenase-1 levels. J Biol Chem. 2007;282:11038-46 pubmed
- Muraoka T, Hizuka N, Fukuda I, Ishikawa Y, Ichihara A. Mechanism of repression of 11?-hydroxysteroid dehydrogenase type 1 by growth hormone in 3T3-L1 adipocytes. Endocr J. 2014;61:675-82 pubmed..8%). These results suggest that GH directly represses 11?-HSD1 mRNA rather than acting via the IGF-I receptor, and that GH represses H6PDH through locally produced IGF-I. ..
- Yau J, Noble J, Kenyon C, Ludwig M, Seckl J. Diurnal and stress-induced intra-hippocampal corticosterone rise attenuated in 11Î²-HSD1-deficient mice: a microdialysis study in young and aged mice. Eur J Neurosci. 2015;41:787-92 pubmed publisher..This contribution is even greater with ageing. Thus, 11Î²-HSD1 inhibition may be an attractive target for treating cognitive impairments associated with stress or ageing. ..
- Koh E, Kim A, Kim H, Kim J, Park H, Ko M, et al. 11Î²-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes. J Endocrinol. 2015;225:147-58 pubmed publisher..In conclusion, increased 11Î²-HSD1 expression contributes to reduced mitochondrial respiration and adiponectin synthesis in hypertrophic adipocytes. ..
- Wang M, Tian X, Leung L, Wang J, Houvig N, Xiang J, et al. Comparative pharmacokinetics and metabolism studies in lean and diet- induced obese mice: an animal efficacy model for 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) inhibitors. Drug Metab Lett. 2011;5:55-63 pubmed..This study highlights the needs to take caution when extrapolating PK and exposure data from healthy animals to diseased animals in designing pharmacological studies. ..
- Larner D, Morgan S, Gathercole L, Doig C, Guest P, Weston C, et al. Male 11?-HSD1 Knockout Mice Fed Trans-Fats and Fructose Are Not Protected From Metabolic Syndrome or Nonalcoholic Fatty Liver Disease. Endocrinology. 2016;157:3493-504 pubmed publisher..However, global deficiency of 11?-HSD1 did increase markers of hepatic inflammation and suggests a critical role for 11?-HSD1 in restraining the transition to NASH. ..
- Gong R, Morris D, Brem A. Variable expression of 11beta Hydroxysteroid dehydrogenase (11beta-HSD) isoforms in vascular endothelial cells. Steroids. 2008;73:1187-96 pubmed publisher..Changes in 11beta-HSD1 with growth and during repair occurred at the transcription level. Thus, 11beta-HSD1 protein expression predominates in endothelial cells and varies during periods of growth. ..
- Zhang Z, Coutinho A, Man T, Kipari T, Hadoke P, Salter D, et al. Macrophage 11Î²-HSD-1 deficiency promotes inflammatory angiogenesis. J Endocrinol. 2017;234:291-299 pubmed publisher..Here, we generated Hsd11b1MKO mice with LysM-Cre mediated deletion of Hsd11b1 to investigate whether 11Î..
- Loerz C, Staab Weijnitz C, Huebbe P, Giller K, Metges C, Rimbach G, et al. Regulation of 11?-hydroxysteroid dehydrogenase type 1 following caloric restriction and re-feeding is species dependent. Chem Biol Interact. 2017;276:95-104 pubmed publisher..Overall, the results demonstrate species-dependent differences in regulation of 11?-HSD1 following CR and suggest the presence of an additional regulation step for 11?-HSD1 activity in mouse liver. ..