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Catalyzes the conversion of cortisol to the inactive metabolite cortisone. Modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids.
Gene References into Functions
Sequence defects (16q22.1) cause Monogenic Hypertension Syndrome in children (with muscle weakness in severe forms)as result of apparent mineralocorticoid excess. PMID: 29229168
High systemic 11beta-HSD2 activity in preeclampsia but not in intrauterine growth retardation suggests an increased cortisol deactivation in maternal tissue in preeclampsia rather than in the placenta. PMID: 29523277
Analyses demonstrated a trend in the association between maternal trait anxiety and depression symptoms with placental gene expression of NR3C1. We found a significant interaction with maternal ethnicity. In Caucasians only, prenatal trait anxiety and depressive symptoms were associated with an increase in placental NR3C1 expression, and prenatal life events were associated with a down regulation of HSD11B2 PMID: 29100173
mutations that allow the formation of an inactive dimer, alter substrate/coenzyme binding, or impair structural stability of HSD11B2 yield severe apparent mineralocorticoid excess (AME). In contrast, mutations that cause an indirect disruption of substrate binding or mildly alter intramolecular interactions result in type 2 AME. PMID: 29229831
Six sequence variations were observed. Four mutations were indicated in the coding region of HSD11B2 and the other two in 3'-UTR. Two SNPs: c.468C > A and c.534G > A were found to be in total disequilibrium. High variability in HSD11B2 sequence was indicated in the study population, but the relevance of observed SNPs to gestational hypertension or pre-eclampsia development was not confirmed. PMID: 27686600
the role of 11beta-HSD2 in determining birth weight PMID: 28502862
SUMOylation of 11beta-HSD2 at residue K266 modulates cortisol-mediated MR nuclear translocation independently of effects on transactivation. PMID: 28938454
11beta-HSD2 activity is not reduced in patients with drug resistant hypertension, suggesting that variation in the conversion of cortisol to cortisone does not contribute to development of antihypertensive treatment resistance. PMID: 28180242
abundantly localized in syncytial layer of the chorionic villi and the decidual epithelium PMID: 27697223
The data demonstrate for the first time that 11b- HSD2 plays a key role in the pathophysiology of malignant epidermal cells. PMID: 28797028
DNA sequence analysis of affected members of Apparent mineralocorticoid excess family revealed homozygous c.799A>G mutations within exon 4 of HSD11B2, corresponding to a p.T267A mutation of 11betaHSD2. PMID: 27526338
activation of Hedgehog signaling is crucial for the upregulation and maintenance of 11beta-HSD2 expression in placenta PMID: 27379371
enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11beta-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11beta-HSD2 gene. PMID: 28302719
Sensitivity to glucocorticoids did not appear to be mediated by changes in the expression of the beta variant of the glucocorticoid receptor or the 11-beta hydroxysteroid dehydrogenase 2 isozyme. PMID: 26963327
Review of the role of HSD11B2 in pregnancy complications, fetal diseases, and later life morbidity. PMID: 27018008
Since increased DNA methylation in HSD11B2 and FKBP5 are seen in a minority of bisulfite sequencing clones, these epigenetic changes, and functional consequences, may affect subpopulations of placental cells. PMID: 27013342
significant positive correlation between DNA methylation of 11beta-HSD2 CpG 1 in infants and maternal sensitivity. PMID: 26822444
The 11beta-HSD2 expression decreased in pre-eclamptic women of Chinese Han ethnicity, but was not interrelated with the promoter methylation status. PMID: 25331012
zearalenone is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as kidney and placentas. PMID: 26798634
Infants with the high-risk neurobehavioral profile showed more methylation than infants with the low-risk neurobehavioral profile at CpG3 for NR3C1 and less methylation of CpG3 for HSD11B2. PMID: 26585459
The CA-repeat length did not influence BP levels or serum F/E ratios in pediatric subjects. However, the serum F/E ratio was associated with BP, suggesting a role of 11betaHSD2 in mineralocorticoid hypertension. PMID: 25907225
growth potential of fetus related to the 11beta-HSD2 expression in the placenta, and 11beta-HSD2 expression related to the trace metals status of the mother PMID: 26462907
maternal depression and anxiety may impact on fetal programming by down-regulating HSD11B2, and antidepressant treatment alone is unlikely to protect against this effect. PMID: 26593902
Data show that glucocorticoid response genes NR3C1, ADCYAP1R1 and HSD11B2 were relatively hypomethylated whereas FKBP5 was hypermethylated. PMID: 26343289
No interaction was found between HSD11B2 and exposure during pregnancy, but individuals with the A allele of rs5479 had an increased risk of schizophrenia after exposure at age 3-9 years PMID: 26115144
11betaHSD2 inhibition suppressed lung tumor growth and invasion in association with increased tissue active glucocorticoid levels, decreased COX-2 expression, inhibition of ERK and mTOR signaling pathways. PMID: 26011146
A novel HSD11B2 functional mutation accounting for an Ala221Gly substitution causes Apparent mineralocorticoid excess. The hypertension phenotype is also epigenetically modulated by HSD11B2 methylation in subjects heterozygous for the mutation PMID: 26126204
infants with low NR3C1 methylation but high HSD11B2 methylation had lower excitability scores; those with high NR3C1 methylation but low HSD11B2 methylation had more asymmetrical reflexes PMID: 25459891
Insulin reduced the 11beta-HSD2 activity in cancer colon cell lines (HCT116, SW620 and HT-29) at the transcriptional level, in a time and dose dependent manner. PMID: 25133511
Preeclampsia reduces methylation level at fetal HSD11B2 promoter. PMID: 25200528
hypertensivesThe 11bHSD2 polymorphism-derived allele frequency was very low, completely absent in controls and no homozygous mutants were found PMID: 25572238
variants of HSD11B2 may be not a cause of obesity. PMID: 24729284
The inverse association of offspring 11beta-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. PMID: 24971590
No correlation was observed between the placental gene expression of 11bHSD-2 and infantile growth at 10 months of age. PMID: 24147632
Results show a link between the site-specific methylation of placental 11beta-hydroxysteroid dehydrogenase (HSD11B2) promoter and the development of intrauterine growth restriction (IUGR). PMID: 24129435
the downregulation of 11HSD2 gene expression is a typical feature of the development of colorectal polypous lesions and their transformation into colorectal adenocarcinoma PMID: 24189979
fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration PMID: 24685985
placental 11bHSD2 expression is significantly reduced in pregnancies complicated by intrahepatic cholestasis of pregnancy. PMID: 24262137
Increased glucocorticoid exposure as a consequence of reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is likely to be a critical determinant of growth in early life PMID: 24517145
analysis of placental 11-B hydroxysteroid dehydrogenase methylation patterns and how they relate to prenatal socioeconomic adversity PMID: 24040322
Data suggest that placental HSD11B2 mRNA expression during prolonged pregnancy is higher in women who do not respond to induction of labor than in responders and in women who enter labor spontaneously. PMID: 24054540
Data suggest that expression of HSD11B2 in placenta/trophoblast cells is regulated, in part, via the ERK1/2 (mitogen-activated protein kinases 3/1) signaling pathway; this pathway mediates cadmium chloride repression of placental HSD11B2 activity. PMID: 23966319
HSD11B2 CA-repeat genotype is not associated with hypertension itself, but with renal sodium excretion, probably through salt intake/appetite. PMID: 23446772
11beta-HSD2 expression can be modulated by PPARalpha and PPARgamma in placental trophoblasts through Sp-1 PMID: 24169559
HSD11B1 and HSD11B2 single nucleotide polymorphisms in hypertensive disorders in pregnancy. PMID: 23659736
Genotyping indicated no hypertension related mutations in the coding region and short introns of HSD11B2 PMID: 23303402
genetic association studies in Japan: Data suggest that in normal subjects total CA-repeat length in HSD11B2 is negatively correlated with insulin secretion; subjects with longer CA repeats in HSD11B2 are more susceptible to glucose intolerance. PMID: 23357976
Data suggest that interaction of p300/Sp1 (lysine acetyltransferase 2B/transcription factor Sp1) with HSD11B2 promoter plays crucial role in histone acetylation in syncytiotrophoblasts; these interactions may be important in placentation. PMID: 23714681
cortisol/cortisone ratio increased with age, but cortisone decreased, suggesting decrease in 11beta-HSD2 activity. Results suggest that cortisol-mediated activation of mineralocorticoid receptor may explain blood pressure increase in elderly subjects. PMID: 23443726
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Involvement in disease
Apparent mineralocorticoid excess (AME)
Subcellular Location
Microsome. Endoplasmic reticulum.
Protein Families
Short-chain dehydrogenases/reductases (SDR) family
Tissue Specificity
Expressed in kidney, pancreas, prostate, ovary, small intestine and colon. At midgestation, expressed at high levels in placenta and in fetal kidney and, at much lower levels, in fetal lung and testis.