Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-.
A low-affinity 11 beta-hydroxysteroid dehydrogenase found in a variety of tissues, most notably in LIVER; LUNG; ADIPOSE TISSUE; vascular tissue; OVARY; and the CENTRAL NERVOUS SYSTEM. The enzyme acts reversibly and can use either NAD or NADP as cofactors.
An high-affinity, NAD-dependent 11-beta-hydroxysteroid dehydrogenase that acts unidirectionally to catalyze the dehydrogenation of CORTISOL to CORTISONE. It is found predominantly in mineralocorticoid target tissues such as the KIDNEY; COLON; SWEAT GLANDS; and the PLACENTA. Absence of the enzyme leads to a fatal form of childhood hypertension termed, APPARENT MINERALOCORTICOID EXCESS SYNDROME.
A class of enzymes that catalyzes the oxidation of 17-hydroxysteroids to 17-ketosteroids. EC 1.1.-.
Catalyze the oxidation of 3-hydroxysteroids to 3-ketosteroids.
Hydroxysteroid dehydrogenases that catalyzes the reversible conversion of CORTISOL to the inactive metabolite CORTISONE. Enzymes in this class can utilize either NAD or NADP as cofactors.
A group of enzymes that catalyze the reversible reduction-oxidation reaction of 20-hydroxysteroids, such as from a 20-ketosteroid to a 20-alpha-hydroxysteroid (EC 1.1.1.149) or to a 20-beta-hydroxysteroid (EC 1.1.1.53).
A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.
A 3-hydroxysteroid dehydrogenase which catalyzes the reversible reduction of the active androgen, DIHYDROTESTOSTERONE to 5 ALPHA-ANDROSTANE-3 ALPHA,17 BETA-DIOL. It also has activity towards other 3-alpha-hydroxysteroids and on 9-, 11- and 15- hydroxyprostaglandins. The enzyme is B-specific in reference to the orientation of reduced NAD or NADPH.
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
Enzymes that catalyze the oxidation of estradiol at the 17-hydroxyl group in the presence of NAD+ or NADP+ to yield estrone and NADH or NADPH. The 17-hydroxyl group can be in the alpha- or beta-configuration. EC 1.1.1.62
A naturally occurring glucocorticoid. It has been used in replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisone itself is inactive. It is converted in the liver to the active metabolite HYDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726)
Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2.
A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)
Reversibly catalyze the oxidation of a hydroxyl group of carbohydrates to form a keto sugar, aldehyde or lactone. Any acceptor except molecular oxygen is permitted. Includes EC 1.1.1.; EC 1.1.2.; and 1.1.99.
The rate dynamics in chemical or physical systems.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
A metabolite of TESTOSTERONE or ANDROSTENEDIONE with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.
A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of NAD. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of NADH and hydrogen.
An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC 1.1.1.70.
Enzymes that catalyze the dehydrogenation of GLYCERALDEHYDE 3-PHOSPHATE. Several types of glyceraldehyde-3-phosphate-dehydrogenase exist including phosphorylating and non-phosphorylating varieties and ones that transfer hydrogen to NADP and ones that transfer hydrogen to NAD.
An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.
Cytoplasmic proteins that specifically bind MINERALOCORTICOIDS and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA.
An enzymes that catalyzes the reversible reduction-oxidation reaction of 20-alpha-hydroxysteroids, such as from PROGESTERONE to 20-ALPHA-DIHYDROPROGESTERONE.
An enzyme that catalyzes the dehydrogenation of inosine 5'-phosphate to xanthosine 5'-phosphate in the presence of NAD. EC 1.1.1.205.
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.
Decrease in existing BODY WEIGHT.
Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.
A hereditary disease characterized by childhood onset HYPERTENSION, hypokalemic alkalosis, and low RENIN and ALDOSTERONE secretion. It results from a defect in the activity of the 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 enzyme which results in inadequate conversion of CORTISOL to CORTISONE. The build up of unprocessed cortisol to levels that stimulate MINERALOCORTICOID RECEPTORS creates the appearance of having excessive MINERALOCORTICOIDS.
A group of CORTICOSTEROIDS primarily associated with water and electrolyte balance. This is accomplished through the effect on ION TRANSPORT in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by PLASMA VOLUME, serum potassium, and ANGIOTENSIN II.
A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)

High dietary potassium chloride intake augments rat renal mineralocorticoid receptor selectivity via 11beta-hydroxysteroid dehydrogenase. (1/271)

Glucocorticoid access to renal corticosteroid receptors is regulated by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), converting 11beta-hydroxyglucocorticoids into inactive 11-ketones. This mechanism plays a key role in maintaining normal salt-water homeostasis and blood pressure. To study whether renal cortical proximal and distal tubular 11beta-HSDs are modulated, upon shifting the electrolyte status (and may thereby contribute to adjusting the salt-water homeostasis), rats were treated for 14 days with diets with low (0.058 w/w%), normal (0.58%, which is the KCl content of standard European laboratory rat food) or high (5.8%) potassium chloride content. In proximal tubules, dietary KCl had no effect regarding corticosterone 11beta-oxidation in intact cells as well as 11beta-HSD1 and 11beta-HSD2 protein (Western blotting) and mRNA levels (semi-quantitative RT-PCR). In distal tubules, the low KCl diet also had no effect. However, distal tubules of rats fed the high KCl diet showed increased corticosterone 11beta-oxidation rates (1.6-fold, P<0.01) and 11beta-HSD2 protein (4-fold, P<0.01), whereas 11beta-HSD1 protein was decreased (no longer detected, P<0.05). Distal tubular 11beta-HSD mRNA levels were not changed upon dietary treatment. Our results suggest that upon dietary KCl loading distal tubular mineralocorticoid receptor selectivity for aldosterone is increased because of enhanced corticosterone 11beta-oxidation. This may contribute to the fine-tuning of salt-water homeostasis by the kidney.  (+info)

Full induction of rat myometrial 11beta-hydroxysteroid dehydrogenase type 1 in late pregnancy is dependent on intrauterine occupancy. (2/271)

The 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) enzyme catalyses the conversion of the biologically inert glucocorticoid 11-dehydrocorticosterone to active corticosterone (11-oxoreductase activity) in vivo, and it is dramatically up-regulated in uterine myometrium in the days leading up to parturition. 11beta-HSD-1 is likely to enhance local concentrations of glucocorticoid within the myometrium and thus facilitate uterine contractility, but the stimulus for the increase in myometrial 11beta-HSD-1 is unknown. The objective of the present study was to test whether the induction of myometrial 11beta-HSD-1 is dependent on uterine occupancy or systemic hormonal signals of late pregnancy. This involved use of a unilateral pregnancy (ULP) model in which the gravid and nongravid uterine horns are both exposed to the normal systemic hormonal milieu of pregnancy. Western blot analysis showed that the 11beta-HSD-1 signal was only partially induced in the nongravid horn of ULP rats on Day 22 of pregnancy (term: Day 23). Moreover, artificial distension of this nongravid horn had no effect on myometrial 11beta-HSD-1 immunoreactivity or bioactivity at either Day 16 or Day 22 of pregnancy. Removal of fetuses and placentas on Day 18 reduced myometrial 11beta-HSD-1 bioactivity 4 days later, and this effect was not overcome by artificial maintenance of uterine distension. In contrast, after fetectomy at Day 18 (i.e., removal of the fetus but not placenta), myometrial 11beta-HSD-1 bioactivity was largely maintained on Day 22, indicative of placental support for myometrial 11beta-HSD-1 over this period. In conclusion, our data show that full induction of myometrial 11beta-HSD-1 expression and associated 11-oxoreductase bioactivity late in rat pregnancy is dependent upon intrauterine occupancy. Although the hormonal milieu of late pregnancy appears to stimulate myometrial 11beta-HSD-1 marginally, full induction clearly requires an additional stimulus. Manipulations involving fetectomy and artificial uterine distension indicate that the placenta provides at least part of this stimulus, but uterine stretch does not appear to play a role.  (+info)

Role of 11beta-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries. (3/271)

The aim of the present study was to demonstrate rapid effects of aldosterone on the Na(+)-H(+) exchanger in strips of human vascular vessels and to determine whether 11beta-hydroxysteroid dehydrogenase enzyme (11beta-HSD) could play a protective role in this response, such as that described for the classic type I mineralocorticoid receptor (MR). The activity of 11beta-HSD isoforms 1 and 2 were measured in fetal and adult arteries. Both isoforms are present in adult and fetal vessels. However, a significant difference in the proportion of each isoform was found. Isoform 1 activity (in pmol x min(-1) x 100 mg(-1) protein) was 42+/-5 in fetal vessels and 29+/-2 in adult arteries, and isoform 2 activity was 78+/-7 in fetal and 12+/-2 in adult tissue. The nongenomic effect of aldosterone on Na(+)-H(+) exchanger activity was measured in strips of chorionic and radial uterine arteries loaded with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein. Recordings of intracellular pH (pH(i)) were made by videofluorescence microscopy. Aldosterone (0.5 nmol/L) rapidly increased pH(i), with a half-maximal effect between 2 and 3 nmol/L in both fetal and adult vessels. Ethylisopropylamiloride, a specific inhibitor of the Na(+)-H(+) exchanger, inhibited this effect. The hormone-mediated increase in pH(i) was unaffected by spironolactone, a classic antagonist of MR, but was completely blocked by RU28318. Cortisol (up to 1 micromol/L) had no effect on pH(i), but when applied in the presence of carbenoxolone, a dramatic increase in Na(+)-H(+) exchanger activity was evident. The increments on pH(i) for each cortisol concentration were similar to those observed for aldosterone. These findings suggest that vascular 11beta-HSD plays an active role in maintaining the specificity of the rapid effects of aldosterone.  (+info)

Novel nuclear corticosteroid binding in rat small intestinal epithelia. (4/271)

When small intestinal epithelial cells are incubated with [(3)H]corticosterone, nuclear binding is displaced neither by aldosterone nor RU-28362, suggesting that [(3)H]corticosterone is binding to a site distinct from mineralocorticoid receptor and glucocorticoid receptor. Saturation and Scatchard analysis of nuclear [(3)H]corticosterone binding demonstrate a single saturable binding site with a relatively low affinity (49 nM) and high capacity (5 fmol/microg DNA). Competitive binding assays indicate that this site has a unique steroid binding specificity, which distinguishes it from other steroid receptors. Steroid specificity of nuclear binding mirrors inhibition of the low 11beta-dehydrogenase activity, suggesting that binding may be to an 11beta-hydroxysteroid dehydrogenase (11betaHSD) isoform, although 11betaHSD1 is not present in small intestinal epithelia and 11betaHSD2 does not colocalize intracellularly with the binding site. In summary, a nuclear [(3)H]corticosterone binding site is present in small intestinal epithelia that is distinct from other steroid receptors and shares steroid specificity characteristics with 11betaHSD2 but is distinguishable from the latter by its distinct intracellular localization.  (+info)

Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta -hydroxysteroid dehydrogenase type 1 expression and activity. (5/271)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been shown to play an important role in the regulation of expression of a subclass of adipocyte genes and to serve as the molecular target of the thiazolidinedione (TZD) and certain non-TZD antidiabetic agents. Hypercorticosteroidism leads to insulin resistance, a variety of metabolic dysfunctions typically seen in diabetes, and hypertrophy of visceral adipose tissue. In adipocytes, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) converts inactive cortisone into the active glucocorticoid cortisol and thereby plays an important role in regulating the actions of corticosteroids in adipose tissue. Here, we show that both TZD and non-TZD PPARgamma agonists markedly reduced 11beta-HSD-1 gene expression in 3T3-L1 adipocytes. This diminution correlated with a significant decrease in the ability of the adipocytes to convert cortisone to cortisol. The half-maximal inhibition of 11beta-HSD-1 mRNA expression by the TZD, rosiglitazone, occurred at a concentration that was similar to its K(d) for binding PPARgamma and EC(50) for inducing adipocyte differentiation thereby indicating that this action was PPARgamma-dependent. The time required for the inhibitory action of the TZD was markedly greater for 11beta-HSD-1 gene expression than for leptin, suggesting that these genes may be down-regulated by different molecular mechanisms. Furthermore, whereas regulation of PPARgamma-inducible genes such as phosphoenolpyruvate carboxykinase was maintained when cellular protein synthesis was abrogated, PPARgamma agonist inhibition of 11beta-HSD-1 and leptin gene expression was ablated, thereby supporting the conclusion that PPARgamma affects the down-regulation of 11beta-HSD-1 indirectly. Finally, treatment of diabetic db/db mice with rosiglitazone inhibited expression of 11beta-HSD-1 in adipose tissue. This decrease in enzyme expression correlated with a significant decline in plasma corticosterone levels. In sum, these data indicate that some of the beneficial effects of PPARgamma antidiabetic agents may result, at least in part, from the down-regulation of 11beta-HSD-1 expression in adipose tissue.  (+info)

Functional expression, characterization, and purification of the catalytic domain of human 11-beta -hydroxysteroid dehydrogenase type 1. (6/271)

11-beta-hydroxysteroid dehydrogenase type 1 catalyzes the conversion of cortisone to hormonally active cortisol and has been implicated in the pathogenesis of a number of disorders including insulin resistance and obesity. The enzyme is a glycosylated membrane-bound protein that has proved difficult to purify in an active state. Extracted enzyme typically loses the reductase properties seen in intact cells and shows principally dehydrogenase activity. The C-terminal catalytic domain is known to contain a disulfide bond and is located within the lumen of the endoplasmic reticulum, anchored to the membrane by a single N-terminal transmembrane domain. We report here the functional expression of the catalytic domain of the human enzyme, without the transmembrane domain and the extreme N terminus, in Escherichia coli. Moderate levels of soluble active protein were obtained using an N-terminal fusion with thioredoxin and a 6xHis tag. In contrast, the inclusion of a 6xHis tag at the C terminus adversely affected protein solubility and activity. However, the highest levels of active protein were obtained using a construct expressing the untagged catalytic domain. Nonreducing electrophoresis revealed the presence of both monomeric and dimeric disulfide bonded forms; however, mutation of a nonconserved cysteine residue resulted in a recombinant protein with no intermolecular disulfide bonds but full enzymatic activity. Using the optimal combination of plasmid construct and E. coli host strain, the recombinant protein was purified to apparent homogeneity by single step affinity chromatography. The purified protein possessed both dehydrogenase and reductase activities with a K(m) of 1.4 micrometer for cortisol and 9.5 micrometer for cortisone. This study indicates that glycosylation, the N-terminal region including the transmembrane helix, and intermolecular disulfide bonds are not essential for enzyme activity and that expression in bacteria can provide active recombinant protein for future structural and functional studies.  (+info)

A transgenic model of visceral obesity and the metabolic syndrome. (7/271)

The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1). We created transgenic mice overexpressing 11beta HSD-1 selectively in adipose tissue to an extent similar to that found in adipose tissue from obese humans. These mice had increased adipose levels of corticosterone and developed visceral obesity that was exaggerated by a high-fat diet. The mice also exhibited pronounced insulin-resistant diabetes, hyperlipidemia, and, surprisingly, hyperphagia despite hyperleptinemia. Increased adipocyte 11beta HSD-1 activity may be a common molecular etiology for visceral obesity and the metabolic syndrome.  (+info)

Correlation between decrease of 11beta-hydroxysteroid dehydrogenase activity and hypokalemia induced by furosemide in rats. (8/271)

AIM: To investigate the correlation between decrease of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity and hypokalemia induced by furosemide (Fur) in rats. METHODS: SD rats were given single dose or successive doses of Fur by gavage. The activity of 11beta-HSD was evaluated by measuring the ratio of 11-dehydrocorticosterone (A) and corticosterone (B) in urine and conversion rate of B to A in renal cortex microsome preparation was determined with HPLC. RESULTS: After giving single dose of Fur (40, 100, and 250 mg/kg) or multiple doses of Fur (10, 20, and 100 mg/kg, bid x 20 d), the ratio of A/B was reduced by 29.0 %, 58.6 %, and 60.9 % at 0 - 2 h; 14.4 %, 36.0 %, and 44.9 %, respectively; the conversion rate of B to A was decreased by 29 %, 33 %, and 37 %; 6 %, 17 %, and 23 %, respectively. The serum potassium was significantly reduced by multiple doses of Fur (20 and 100 mg/kg, bid x 20 d) (P < 0.01). The reduction in serum potassium was positively correlated with the lowering of A/B ratio and the conversion of B to A (P < 0.01). CONCLUSION: The inhibition of renal 11beta-HSD activity may be another new biochemical mechanism for hypokalemia induced by Fur.  (+info)

TY - JOUR. T1 - 11 beta-hydroxysteroid dehydrogenase type 2 in mouse aorta - Localization and influence on response to glucocorticoids. AU - Christy, C AU - Hadoke, P W F AU - Paterson, J M AU - Mullins, J J AU - Seckl, J R AU - Walker, B R PY - 2003/10. Y1 - 2003/10. N2 - Both isozymes of 11 beta-hydroxysteroid dehydrogenase, which interconvert active and inactive glucocorticoids, are expressed in the mouse aortic wall. Mice deficient in 11HSD type 2 ( which converts active corticosterone into inert 11-dehydrocorticosterone) have hypertension and impaired endothelial nitric oxide activity. It has been suggested that 11HSD2 influences vascular function directly by limiting glucocorticoid-mediated inhibition of endothelium-derived nitric oxide. This study sought to determine (1) the cellular distribution of the 11HSD isozymes within the mouse aortic wall and (2) the influence of 11HSD2 on direct glucocorticoid-mediated changes in aortic function. Mouse aortas were separated into their component ...
The global epidemic of obesity has heightened the need to understand the mechanisms that underpin its pathogenesis. Clinical observations in patients with Cushings syndrome have highlighted the link between cortisol and central obesity. However, although circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) has been postulated as a pathogenic mechanism. Although levels of expression of 11betaHSD1 in adipose tissue in human obesity are debated in the literature, global inhibition of 11betaHSD1 improves insulin sensitivity. We have determined the effects of significant weight loss on cortisol metabolism and adipose tissue 11betaHSD1 expression after 10-wk ingestion of a very low calorie diet in 12 obese patients (six men and six women; body mass index, 35.9 +/- 0.9 kg/m2; mean +/- SE). All patients achieved significant weight loss (14.1 +/- 1.3% of initial body weight). Total fat
KEE316Hu, HSD11b1L; SCDR10; HSD3; SDR26C2; 11-Beta Hydroxysteroid Dehydrogenase Type 1 Like Protein; Short chain dehydrogenase/reductase family 26C member 2 | Products for research use only!
4FAL: Crystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 in complex with 3-((3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl)-N-methylbenzamide (80)
Glucocorticoids are important regulators of glucose, lipid and protein metabolism, acting mainly in the liver, adipose tissue and muscle. Chronic glucocorticoid excess is associated with clinical features, such as insulin resistance, visceral obesity, hypertension, and dyslipidemia, which also represent the classical hallmarks of the metabolic syndrome. Elevenbeta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), a key intracellular enzyme which catalyses the conversion of inactive cortisone to active cortisol, has been implicated in the development of the metabolic syndrome. The shift of this reaction towards cortisol generation may lead to tissutal overexposure to glucocorticoids even with normal circulating cortisol levels. The most robust evidence in support of a pathogenetic role of this enzyme in the development of the metabolic syndrome has been reported in experimental animals, whereas results of human studies are less convincing with several case control and cross-sectional studies ...
Local brain amplification of glucocorticoids (GCs) by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a pivotal role in age-related memory deficits. 11β-HSD1 deficient mice are protected from...
The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) is thought to protect the non-selective mineralocorticoid receptor from occupation by glucocorticoids, and to modulate access of glucocorticoids to glucocorticoid receptors resulting in protection of the fetus and gonads. A ubiquitous low …
|i|Background|/i|. Glucocorticoid excess has been linked to clinical observations associated with the pathophysiology of metabolic syndrome. The intracellular glucocorticoid levels are primarily modulated by 11|i|β|/i|-hydroxysteroid dehydrogenase type 1 (11|i|β|/i|-HSD1) enzyme that is highly expressed in key metabolic tissues including fat, liver, and the central nervous system.|i| Methods|/i|. In this study we synthesized a set of novel tetrahydrothiazolopyridine derivatives, TR-01–4, that specifically target 11|i|β|/i|-HSD1 and studied their ability to interfere with the glucocorticoid and lipid metabolism in the 3T3-L1 adipocytes.|i| Results|/i|. Based on the docking model and structure-activity relationships, tetrahydrothiazolopyridine derivatives TR-02 and TR-04 showed the highest potency against 11|i|β|/i|-HSD1 by dose-dependently inhibiting conversion of cortisone to cortisol (IC|sub|50|/sub| values of 1.8 |i|μ|/i|M and 0.095 |i|μ|/i|M,
Q9EQC1: 3 beta-hydroxysteroid dehydrogenase type 7; 3 beta-hydroxysteroid dehydrogenase type VII; 3-beta-HSD VII; 3-beta-hydroxy-Delta(5)-C27 steroid oxidoreductase; C(27) 3-beta-HSD; 1.1.1.-; Cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase; 1.1. ...
Human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a steroid-converting enzyme that has long been known to play critical roles in estradiol synthesis and more recently in dihydrotestosterone (DHT) inactivation, showing a dual function that promotes breast cancer cell proliferation. Previously, we reported the first observation of the influence of the enzyme on endogenous estrogen-responsive gene expression. Here, we demonstrate the impact of 17β-HSD1 expression on the breast cancer cell proteome and investigate its role in cell migration. 17β-HSD1 was stably transfected in MCF7 cells and the proteome of the generated cells overexpressing 17β-HSD1 (MCF7-17βHSD1 cells) was compared to that of the wild type MCF7 cells. Proteomics study was performed using two-dimensional gel electrophoresis followed by mass spectrometry analysis of differentially expressed protein spots. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to investigate the transcription of individual gene.
4FAL: 3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids; a New Class of Highly Potent and Selective Inhibitors of the Type 5 17-beta-hydroxysteroid Dehydrogenase AKR1C3
17beta-hydroxysteroid dehydrogenase type12 (HSD17B12) has been demonstrated to be involved in regulation of in situ biosynthesis of estradiol (E2). HSD17B12 expression was reported in breast carcinomas but its functions have remained unknown. Therefore, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases in order to analyze an association of the enzyme expression with intratumoral E2 production. No significant correlations were detected between intratumoral HSD17B12expression and E2 concentration.These findings suggest that the presence of HSD17B12 in carcinoma cells contributes to a development of human breast carcinoma via a pathway other than in situ E2 biosynthesis.
Expression in E. coli and tissue distribution of the human homologue of the mouse Ke 6 gene, 17beta-hydroxysteroid dehydrogenase type 8 ...
The relationship between stress, cortisol and an increase in body fat has been well established. However, new research has identified a little known enzyme deep within fat cells called 11 beta-hydroxysteroid dehydrogenase-1 or HSD. The HSD enzyme converts the inactive form of cortisol (called cortisone) into the active, fat storing form called cortisol.. Researchers in Germany noted that the rate of activity of the HSD enzyme determines the rate of fat storage in the individual. When individuals were experiencing high levels of HSD activity, no amount of exercise, diet or stress management are able to prevent fat gain.. The activity of the HSD enzyme increases with age. Women and men in their thirties and forties can experience as much a 300% increase in HSD activity compared to an individual in their twenties. This may account to for steady increase in stubborn body fat observed in individuals as they age.. ...
Journal Article: On-column ligand exchange for structure-based drug design: a case study with human 11[beta]-hydroxysteroid dehydrogenase type 1 ...
The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is selectively expressed in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor. A diminished activity causes salt-sensitive hypertension. The mechanism of the variable and distinct 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) expression in the cortical collecting duct is poorly understood. Here, we analyzed for the first time whether the 11β-HSD2 expression is modulated by microRNAs (miRNAs). In silico analysis revealed 53 and 27 miRNAs with potential binding sites on human or rat HSD11B2 3′-untranslated region. A reporter assay demonstrated 3′-untranslated region-dependent regulation of human and rodent HSD11B2. miRNAs were profiled from cortical collecting ducts and proximal convoluted tubules. Bioinformatic analyses showed a distinct clustering for cortical collecting ducts and proximal convoluted tubules with 53 of 375 miRNAs, where 13 were predicted to bind to the ...
11 beta-hydroxysteroid dehydrogenase (11 beta HSD) has both dehydrogenase (11 beta DH) and reductase (11 beta R) activities, which catalyse the interconversion of cortisol and cortisone, and prednisolone and prednisone. This enzyme confers specificity
11ß-hydroxysteroid dehydrogenase type1 (11β-HSD1) converts inactive glucocorticoids to active glucocorticoids which, in excess, leads to development of the various risk factors of the metabolic syndrome. Recent studies clearly suggest that both increased expression and activity of 11β-HSD1 in metabolically active tissues such as liver, muscle and adipose are implicated in tissue specific dysregulation which collectively contribute to the whole body pathology seen in metabolic syndrome. In the present study we have evaluated CNX-010-49, a highly potent, selective and pan tissue acting 11β-HSD1 inhibitor, for its potential to modulate multiple risk factors of the metabolic syndrome. Male C57B6/J mice on high fat diet (DIO mice) were orally dosed with CNX-010-49 (30 mg/kg twice daily; n = 8) or vehicle for 10 weeks. Fasting glucose, triglycerides, glycerol, free fatty acids, body weight and feed intake were measured at selected time points. At the end of the treatment an OGTT and subsequently organ
Similar phenotypes in 46,XY DSD have different etiopathogenesis. Androgen (A) synthesis are rare respect to A action/metabolism defects. The most frequent cause in the former group is a mutation of HSD17B3, gene encoding for an enzyme (17BHSD3) converting delta4-androstenedione (D4) into testosterone (T). Homozygotes/compound heterozygotes have testes, male wolffian structures, completely female (F) or mildly virilized external genitalia (EG). Pts with not palpable testes may appear as F, but they virilize at puberty for the increase in serum T. Our patient (12-yrs-old. 46,XY) for FEG at birth was raised as girl until puberty, when clitoris enlargement (, 4 cm) and male pattern of body hair and timbre of voice appeared. The EG corresponded to Prader stage III. Pelvic echography: two hypoechogenic ovoid masses in inguinal regions, compatible with testes, no Müllerian structures, echogenic structure (20x5mm) like hypoplastic uterus, posteriorly to the bladder. T synthesis: reduced before (3.3 ...
Bile acids (BAs) are important modulators of metabolic functions such as lipid, triglyceride and glucose homeostasis. Intrahepatic accumulation of BAs is known to cause liver injury in cholestatic conditions, where normal trans-hepatic BA flow is impaired due to pathological conditions or induced by toxic drugs. Therefore, it is important to understand the mechanisms of BA homeostasis regulation and to identify novel players and characterize their functions. The main goal of the present work was to investigate the impact of altered hepatic glucocorticoid activation by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on BA homeostasis and to unravel the mechanisms of adaptations in a scenario of impaired 11β-HSD1 function. In order to achieve this goal, we developed and validated an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the quantification of a total of 24 BAs, including 11 unconjugated, 6 glycine-conjugated and 7 ...
Status of 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) immunoreactivity was significantly higher in invasive lobular carcinoma (ILC) than in invasive duc
TY - JOUR. T1 - The NGFI-B family of transcription factors regulates expression of 3β-hydroxysteroid dehydrogenase type 2 in the human ovary. AU - Havelock, Jon C.. AU - Smith, Allison L.. AU - Seely, Jeremiah B.. AU - Dooley, Christina A.. AU - Rodgers, Raymond J.. AU - Rainey, William E.. AU - Carr, Bruce R.. N1 - Funding Information: The authors would like to thank Bobbie Mayhew for her technical support. This work was supported by National Institutes of Health grant T32-HD007190 (BRC).. PY - 2005/2. Y1 - 2005/2. N2 - The nerve growth factor-induced clone B (NGFI-B) family of transcription factors are orphan members of the steroid hormone receptor superfamily. The NGFI-B expression was recently shown in the rat ovarian tissue and appears to be regulated by gonadotrophins. The purpose of our study was to investigate the role of the three members of this family [NGFI-B, Nur-related factor 1 (NURR1) and neuron derived orphan receptor 1 (NOR-1)] in the transcription of genes that encode key ...
The biological activity of steroid hormones is regulated at the pre-receptor level by several enzymes including 17 beta-hydroxysteroid dehydrogenases (17 beta -HSD). The latter are present in many microorganisms, invertebrates and vertebrates. Dysfunctions in human 17 beta-hydroxysteroid dehydrogenases result in disorders of biology of reproduction and neuronal diseases, the enzymes are also involved in the pathogenesis of various cancers. 17 beta-hydroxysteroid dehydrogenases reveal a remarkable multifunctionality being able to modulate concentrations not only of steroids but as well of fatty and bile acids. Current knowledge on genetics, biochemistry and medical implications is presented in this review.
17 beta-hydroxysteroid dehydrogenases catalyze the oxidoreduction of hydroxy/oxo groups at position C17 of steroid hormones, thereby constituting a prereceptor control mechanism of hormone action. At present, 11 different mammalian 17 beta-hydroxysteroid dehydrogenases have been identified, catalyzing the cell- and steroid-specific activation and inactivation of estrogens and androgens. The human type 10 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD-10) is a multifunctional mitochondrial enzyme that efficiently catalyzes the oxidative inactivation at C17 of androgens and estrogens. However, it also mediates oxidation of 3 alpha-hydroxy groups of androgens, thereby reactivating androgen metabolites. Finally, it is involved in beta-oxidation of fatty acids by catalyzing the L-hydroxyacyl CoA dehydrogenase reaction of the beta-oxidation cycle. These features and expression profiles suggest a critical role of 17 beta-HSD-10 in neurodegenerative and steroid-dependent cancer forms. Since no three
TY - JOUR. T1 - Increased in vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone. AU - Sandeep, Thekkepat C. AU - Andrew, Ruth. AU - Homer, Natalie Z M. AU - Andrews, Robert C. AU - Smith, Ken. AU - Walker, Brian R. PY - 2005. Y1 - 2005. N2 - 11beta-Hydroxysteroid dehydrogenase type 1 (11HSD1) regenerates cortisol from cortisone within adipose tissue and liver. 11HSD1 inhibitors may enhance insulin sensitivity in type 2 diabetes and be most efficacious in obesity when 11HSD1 is increased in subcutaneous adipose biopsies. We examined the regeneration of cortisol in vivo in obesity, and the effects of the 11HSD1 inhibitor carbenoxolone. We compared six lean and six obese men and performed a randomized, placebo-controlled crossover study of carbenoxolone in obese men. The obese men had no difference in their whole-body rate of regenerating cortisol (measured with 9,11,12,12-[(2)H(4)]cortisol tracer), ...
Clinical observations have highlighted the link between glucocorticoids and obesity. While exogenous glucocorticoids in excess predispose to the development of central obesity, we have focused on cortisol metabolism within human adipose tissue. 11beta-hydroxysteroid dehydrogenase (11beta-HSD) inter-converts the active glucocorticoid, cortisol, and inactive cortisone. 11beta-HSD1, the only isoform expressed in adipose tissue, acts predominantly as an oxoreductase to generate cortisol. Expression is higher in omental compared to subcutaneous preadipocytes and activity and expression are potently regulated by growth factors and cytokines. Mice over-expressing 11beta-HSD1 specifically within adipocytes develop central obesity. However, the situation is less clear in humans. Globally, there appears to be inhibition of the enzyme, but expression in human obesity is still not fully characterized; its functional role in adipocyte biology remains to be elucidated. In vitro, 11beta-HSD1 appears to function in
Clinical observations have highlighted the link between glucocorticoids and obesity. While exogenous glucocorticoids in excess predispose to the development of central obesity, we have focused on cortisol metabolism within human adipose tissue. 11beta-hydroxysteroid dehydrogenase (11beta-HSD) inter-converts the active glucocorticoid, cortisol, and inactive cortisone. 11beta-HSD1, the only isoform expressed in adipose tissue, acts predominantly as an oxoreductase to generate cortisol. Expression is higher in omental compared to subcutaneous preadipocytes and activity and expression are potently regulated by growth factors and cytokines. Mice over-expressing 11beta-HSD1 specifically within adipocytes develop central obesity. However, the situation is less clear in humans. Globally, there appears to be inhibition of the enzyme, but expression in human obesity is still not fully characterized; its functional role in adipocyte biology remains to be elucidated. In vitro, 11beta-HSD1 appears to function in
There are increasing data on the central role of miRNAs in the development of various diseases, including some kidney and cardiovascular entities.27,32,33 Whether miRNAs and the 3′-UTR of specific players in the field of renal or blood pressure physiology are relevant is yet to be addressed specifically. The 11β-HSD2 is an essential enzyme for blood pressure control.3 Therefore, the mechanisms accounting for its regulation are a prerequisite for understanding blood pressure in health and disease states. Here, we present evidence that HSD11B2 mRNA fulfills the prerequisites to be modulated by miRNAs. Because a multitude of miRNAs directly or indirectly affect the expression of a protein, special emphasis was given to the miRNA expression profile in the CCD, the main site of 11β-HSD2 action.. To the best of our knowledge, the relationship between miRNA and 11β-HSD2 was reported previously only once.34 Shang et al34 starved a human placental cell line (BeWo) from amino acids and observed a ...
11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the conversion of corticosterone to inert 11-dehydrocorticosterone, thus regulating glucocorticoid access to intracellular receptors. This type 1 isoform (11 beta HSD-1) is a bidirectional NADPH(H)-dependent enzyme in vitro and is highly e …
17Beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the NAD(P)(H) dependent oxidoreduction at C17 oxo/beta-hydroxyl groups of androgen and estrogen hormones. This reversible reaction constitutes an important pre-receptor control mechanism for nuclear receptor ligands, since the conversion switches between the 17beta-OH receptor ligands and their inactive 17-oxo metabolites. At present, 14 mammalian 17beta-HSDs are described, of which at least 11 exist within the human genome, encoded by different genes. The enzymes differ in their expression pattern, nucleotide cofactor preference, steroid substrate specificity and subcellular localization, and thus constitute a complex system ensuring cell-specific adaptation and regulation of sex steroid hormone levels. Broad and overlapping substrate specificities with enzymes involved in lipid metabolism suggest interactions of several 17beta-HSDs with other metabolic pathways. Several 17beta-HSDs enzymes constitute promising drug targets, of particular
17Beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the NAD(P)(H) dependent oxidoreduction at C17 oxo/beta-hydroxyl groups of androgen and estrogen hormones. This reversible reaction constitutes an important pre-receptor control mechanism for nuclear receptor ligands, since the conversion switches between the 17beta-OH receptor ligands and their inactive 17-oxo metabolites. At present, 14 mammalian 17beta-HSDs are described, of which at least 11 exist within the human genome, encoded by different genes. The enzymes differ in their expression pattern, nucleotide cofactor preference, steroid substrate specificity and subcellular localization, and thus constitute a complex system ensuring cell-specific adaptation and regulation of sex steroid hormone levels. Broad and overlapping substrate specificities with enzymes involved in lipid metabolism suggest interactions of several 17beta-HSDs with other metabolic pathways. Several 17beta-HSDs enzymes constitute promising drug targets, of particular
STUDY QUESTION: What are the in vivo and in vitro actions of kisspeptin-54 on the expression of genes involved in ovarian reproductive function, steroidogenesis and ovarian hyperstimulation syndrome (OHSS) in granulosa lutein (GL) cells when compared with traditional triggers of oocyte maturation? SUMMARY ANSWER: The use of kisspeptin-54 as an oocyte maturation trigger augmented expression of genes involved in ovarian steroidogenesis in human GL cells including, FSH receptor (FSHR), LH/hCG receptor (LHCGR), steroid acute regulatory protein (STAR), aromatase, estrogen receptors alpha and beta (ESR1, ESR2), 3-beta-hydroxysteroid dehydrogenase type 2 (3BHSD2) and inhibin A (INHBA), when compared to traditional maturation triggers, but did not alter markers of OHSS ...
An exciting era is upon us in terms of new therapies for patients with diabetes, obesity, and metabolic syndrome. One such advance is the ability to selectively manipulate tissue levels of glucocorticoids through targeted inhibition of cortisol metabolic pathways. Perhaps the best paradigm for metabolic syndrome comes from patients with Cushings syndrome, with their characteristic central obesity, glucose intolerance, hypertension, and premature cardiovascular mortality. Although circulating cortisol concentrations are invariably normal in patients with obesity and metabolic syndrome (1), in vitro, in vivo, and clinical studies over the last decade have collectively shown the importance of local generation of cortisol, via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in liver and fat, in mediating many facets of the metabolic syndrome (2). Major pharmaceutical companies are now engaged; over 50 patents have been issued detailing compounds and strategies for selective 11β-HSD1 ...
Rationale Rescuing adverse myocardial redesigning can be an unmet clinical goal and, correspondingly, pharmacological opportinity for its meant reversal are urgently required. cardiac redesigning without influencing the vasculature. Increasing the arsenal of remodeling-reversing medicines to pathways apart from RAAS, a particular inhibitor of 11-hydroxy-steroid dehydrogenase type 1 (11 HSD1), an integral enzyme necessary for producing active glucocorticoids, completely rescued myocardial hypertrophy. This is connected with mitigating the hypertrophy-associated gene personal, including reversing the myosin weighty chain isoform change however in a design distinguishable from that connected with neovascularization-induced reversal. Conclusions Something was developed ideal for determining novel remodeling-reversing medicines operating in various pathways as well as for getting insights to their systems of actions, exemplified right here by uncoupling their vascular impacts. Introduction Cardiac ...
[Inhibitory effect on pig testicular 20 beta-hydroxysteroid dehydrogenase by various inhibitors of steroid metabolizing enzymes].:
The PalmSens SDK is a set of libraries and examples that allows you to develop your own software for EmStat and PalmSens instruments in Visual Studio, Matlab or LabVIEW. ...
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Mutations in HSD3B2, the gene for 3beta-hydroxysteroid dehydrogenase type II (3beta-HSD II) have been detected and activities analysed through the in vitro expression of mutant cDNAs. Two full sibs with male pseudohermaphroditism were found to be double heterozygotes: N100S/266DeltaA. This genotype leads to the most profound loss of 3beta-HSD II enzyme activity (1.3% of normal) described to date in cases without severe salt-loss. One sib (N100S/266DeltaA) is the first reported male case of type II deficiency affected with premature adrenarche. Three apparently independent kindreds had propositi affected with the HSD3B2 mutation A82T/A82T, which is associated with a non salt-losing phenotype with variable expressivity in females. These three families had the same extended HSD3B haplotype and are likely to have inherited the same ancestral mutation. The significance of this finding is discussed in the light of the presence of A82T mutation at a homologous position in pseudogene varphi5 that is ...
Oestrogens play key roles in the development of the majority of breast tumours, a fact that has been exploited successfully in treating breast cancer with tamoxifen, which is a selective oestrogen receptor modulator. In post-menopausal women, oestrogens are synthesised in peripheral hormone-target tissues from adrenally derived precursors. Important in the peripheral fine-tuning of sex hormone levels are the 17β hydroxysteroid dehydrogenases (17βHSDs). These enzymes catalyse the oxidation/reduction of carbon 17β of androgens and oestrogens. Upon receptor binding, the 17β-hydroxy conformation of androgens and oestrogens (testosterone and oestradiol) triggers a greater biological response than the corresponding keto-conformation of the steroids (androstenedione and oestrone), and the 17βHSD enzymes are therefore important mediators in pre-receptor regulation of sex hormone action.. Breast tumours differ substantially with regards to molecular and/or biochemical signatures and thus clinical ...
Carbonyl reduction is a significant step in the biotransformation leading to the elimination, of endogenous and exogenous aldehydes, ketones and quinones. This reaction is mediated by members of the aldo-keto reductase and short-chain dehydrogenase/reductase (SDR) superfamilies. The essential role of these enzymes in protecting organisms from damage by the accumulation of toxic carbonyl compounds is generally accepted, although their physiological roles are not always clear. Recently, the SDR enzyme 11beta-hydroxysteroid dehydrogenase-1 has been identified to perform an important role in the detoxification of non-steroidal carbonyl compounds, in addition to metabolising its physiological glucocorticoid substrates. This review summarises the current knowledge of type-1 11beta-hydroxysteroid dehydrogenase and discusses possible substrate/inhibitor interactions. They might impair either the physiological function of glucocorticoids or the detoxification of non-steroid carbonyl compounds.
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Alterations in glucocorticoid (GC) biosynthesis and metabolism are associated with a variety of pathophysiological disorders including cholestasis, diabetes and other metabolic disorders. Bile acids (BA) are also important modulators of metabolic functions and regulate cholesterol, triglyceride and glucose homeostasis as well as being critical for dietary fat digestion, enterohepatic function, and postprandial thermogenesis. In intact cells and in vivo, the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme converts inactive GC precursors (cortisone in humans, and 11-dehydrocorticosterone in mice and rats) into their active forms (cortisol and corticosterone, respectively) thereby amplifying local intracellular GC levels. Interconversion by 11β-HSD1 of other sterols has also been described. These include conversions of 7keto-cholesterol to 7β-hydroxycholesterol, 7-oxodehydroepiandrosterone (7-oxo-DHEA) to 7α-hydroxy- and 7β-hydroxy DHEA, 7- oxo-lithocholic acid (LCA, a bile acid; ...
Mutagenetic replacements of conserved residues within the active site of the short-chain dehydrogenase/reductase (SDR) superfamily were studied using prokaryotic 3 beta/17 beta-hydroxysteroid dehydrogenase (3 beta/17 beta-HSD) from Comamonas testosteroni as a model system. The results provide novel data to establish Ser 138 as a member of a catalytically important triad of residues also involving Tyr151 and Lys155. A Ser--|Ala exchange at position 138 results in an almost complete (| 99.9%) loss of enzymatic activity, which is not observed with a Ser--|Thr replacement. This indicates that an essential factor for catalysis is the ability of side chain 138 to form hydrogen bond interactions. Mutations in the NAD(H) binding region, in strands beta A, beta D, and adjacent turns, reveal two additional residues, Thr12 and Asn87, which are important for correct binding of the coenzyme and with a differential effect on the reactions catalyzed. Thus, mutation of Thr12 to Ala results in a complete loss of the 3
Glucocorticoid (GC) excess adversely affects skin integrity, inducing thinning and impaired wound healing. Aged skin, particularly that which has been photo-exposed, shares a similar phenotype. Previously, we demonstrated age-induced expression of the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11β-HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11β-HSD1 KO mouse skin phenotype. 11β-HSD1 activity was elevated in aged human and mouse skin and in PE compared with donor-matched photo-protected human biopsies. Age-induced dermal atrophy with deranged collagen structural organization was prevented in 11β-HSD1 KO mice, which also exhibited increased collagen density. We found that treatment of HDFs with physiological concentrations of cortisol inhibited rate-limiting steps in collagen biosynthesis and processing. Furthermore, topical 11β-HSD1 inhibitor treatment ...
Glucocorticoid (GC) excess adversely affects skin integrity, inducing thinning and impaired wound healing. Aged skin, particularly that which has been photo-exposed, shares a similar phenotype. Previously, we demonstrated age-induced expression of the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11β-HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11β-HSD1 KO mouse skin phenotype. 11β-HSD1 activity was elevated in aged human and mouse skin and in PE compared with donor-matched photo-protected human biopsies. Age-induced dermal atrophy with deranged collagen structural organization was prevented in 11β-HSD1 KO mice, which also exhibited increased collagen density. We found that treatment of HDFs with physiological concentrations of cortisol inhibited rate-limiting steps in collagen biosynthesis and processing. Furthermore, topical 11β-HSD1 inhibitor treatment ...
BARNARD L. The Biosynthesis of Adrenal C11-Oxy C21 Steroids, Implicated in 21-Hydroxylase Deficiency - Desoxycortisol and Desoxycortisone and Their Downstream Metabolism. MSc, 2017. 105 pp. Studieleier: SWART AC.. BARNARD M. The characterization of 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) activity towards novel C19 substrates. MSc, 2017. 104 pp. Studieleier: STORBECK K.. BARRY CJ. Modelling the glucocorticoid receptor dimerisation cycle. MSc, 2017. 123 pp. Studieleier: ROHWER JM. Medestudieleier: LOUW A.. BURGER R. Flux balance analysis of Plasmodium falciparum growth and energy metabolism. MSc, 2017. 100 pp. Studieleier: SNOEP JL. Medestudieleier: EICHER JJ.. JOHNSTONE E. Comparative secretome analysis of normal prostate and prostate cancer cell models. MSc, 2017. 134 pp. Studieleier: STORBECK K. Medestudieleier: VLOK NM.. JONKER HI. Evaluation of DNA vaccines against Mycoplasma nasistruthionis sp. nov. str. Ms03 infections in ostriches and the production of IgA heavy chain proteins. ...
Cortisol opposes the activity of anabolic hormones, including testosterone, growth hormone, insulinlike growth factor 1 - a.k.a. IGF-1 - and insulin, although, conversely, the same hormones oppose cortisols catabolic activity. One measure of overtraining is the ratio of testosterone to cortisol - if it tips in favour of cortisol, youve slipped into overtraining. Interestingly, however, one study found that cortisol actually encourages greater activity of free - that is, active - testosterone following exercise by stimulating its release from its protein binder in the blood.1 Another recent study showed that intense training increases cortisol by stimulating the enzyme that converts inactive cortisone into active cortisol.2 Yet another found that, contrary to popular belief, low-intensity exercise not only doesnt increase cortisol but actually lowers it.3 ...
Differentiated OADs for geriatric and post-menopausal population with impact on sarcopenia, visceral adiposity and other metabolic outcomes.. 11HSDβ1 is a member of the short-chain dehydrogenase-reductase family and a key intracellular enzyme which catalyses the conversion of inactive cortisone to active cortisol. Tissue level 11HSDβ1 expression and activity is reported to be high in obese individuals with T2D. Reducing cortisol levels by inhibiting 11HSDβ1 activity in multiple metabolic tissues can provide an important therapeutic handle in these patient populations.. CNX-010-49 is the most advanced candidate from this program fulfilling the TPP of a next generation anti-diabetic, demonstrating significant impact on multiple metabolic parameters without causing HPA activation:. ...
This highly specific HSD17B4 / 17-beta-Hydroxysteroid dehydrogenase 4 antibody is suitable for use in WB, IHC-P and is guaranteed to work as stated on the product data sheet. | R30817
Stort Valley Healthcare, the federation for Stort Valley and Villages practices, continues to thrive in spite of practice pressures. Practices worked together to provide additional appointments for patients in the locality throughout the winter months to help manage the increased demand during this busy period. A new website has been developed which now allows for all the practices and practitioners to have their say and influence decision making at the locality board. An innovative pilot project is taking place to offer testing in practices to see if patients require antibiotics for respiratory tract infections. The federation has also helped develop links with external providers to bring about an improvement in the provision of sexual health services at Herts and Essex Hospital.. ...
"11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocrine Reviews. 25 (5 ... 5-beta THF), reactions for which 5-alpha reductase and 5-beta-reductase are the rate-limiting factors, respectively. 5-Beta ... The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH. Cortisol even has a ... the endogenous type I and type II receptor agonist) or RU28362 (a specific type II receptor agonist) to adrenalectomized ...
... beta}-hydroxysteroid dehydrogenase type 1 activity". Endocrinology. 146 (6): 2539-43. doi:10.1210/en.2005-0117. PMID 15774558. ... "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to ... "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to ... "Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1". ...
... possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processes". J. Steroid Biochem. Mol. Biol. 104 ( ... "CYP7B generates a selective estrogen receptor beta agonist in human prostate". J. Clin. Endocrinol. Metab. 89 (6): 2928-35. doi ... 316 (1): 158-64. doi:10.1016/j.bbrc.2004.02.029. PMID 15003524. Yau JL, Rasmuson S, Andrew R, Graham M, Noble J, Olsson T, ... "Entrez Gene: CYP7B1 cytochrome P450, family 7, subfamily B, polypeptide 1". Stapleton G, Steel M, Richardson M, Mason JO, Rose ...
Cooper MS, Stewart PM (2009). "11Beta-hydroxysteroid dehydrogenase type 1 and its role in the hypothalamus-pituitary-adrenal ... p. 1. Quirke, Viviane (2005). "Making British Cortisone: Glaxo and the development of Corticosteroids in Britain in the 1950s- ... 2010-11-16. Retrieved July 31, 2013. "Prednisone and other corticosteroids: Balance the risks and benefits". MayoClinic.com. ... It must be converted to cortisol by the action of 11β-Hydroxysteroid dehydrogenase type 1. This primarily happens in the liver ...
2005). "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocr. Rev. 25 (5 ... Persu A (2005). "11beta-Hydroxysteroid deshydrogenase: a multi-faceted enzyme". J. Hypertens. 23 (1): 29-31. doi:10.1097/ ... "Entrez Gene: HSD11B2 hydroxysteroid (11-beta) dehydrogenase 2". Geerling, Joel C.; Arthur D. Loewy (September 2009). " ... 1998). "Molecular basis for hypertension in the "type II variant" of apparent mineralocorticoid excess". Am. J. Hum. Genet. 63 ...
"Glucocorticoids and 11beta-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome". Endocrinology Unit, ... "Estrogen reduces 11beta-hydroxysteroid dehydrogenase type 1 in liver and visceral, but not subcutaneous, adipose tissue in rats ... "Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action". Endocrinology ... "Luteinizing hormone induces expression of 11beta-hydroxysteroid dehydrogenase type 2 in rat Leydig cells". Department of ...
11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action". Endocrinology. 142 (4): 1371 ... Seckl JR (January 1997). "11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action?". Front ... There are two types of 11β-Hydroxysteroid dehydrogenases that control cortisol concentration: HSD-11β Type 1 and HSD-11β Type 2 ... The dehydrogenase activity of a HSD-11β converts a 11beta-hydroxysteroid to the corresponding 11-oxosteroid by reducing NADP+ ...
... beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 ... Wake DJ, Walker BR (February 2006). "Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity". Endocrine. 29 (1): ... Agarwal AK (November 2003). "Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I ... "11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas". Journal of ...
3-hydroxysteroid dehydrogenases MeSH D08.811.682.047.436.350.100 - 3alpha-hydroxysteroid dehydrogenase (B-specific) MeSH ... myosin type iii MeSH D08.811.277.040.025.525.843 - myosin type iv MeSH D08.811.277.040.025.525.875 - myosin type v MeSH D08.811 ... dopamine beta-hydroxylase MeSH D08.811.682.690.708.392 - fatty acid desaturases MeSH D08.811.682.690.708.392.312 - beta- ... 20-hydroxysteroid dehydrogenases MeSH D08.811.682.047.436.400.074 - 20alpha-hydroxysteroid dehydrogenase MeSH D08.811.682.047. ...
2003). "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase ... Ikegwuonu FI, Jefcoate CR (1999). "Evidence for the involvement of the fatty acid and peroxisomal beta-oxidation pathways in ... Beutler E, Morrison M (1968). "Localization and characteristics of hexose 6-phosphate dehydrogenase (glucose dehydrogenase)". J ... "An autosomal glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) polymorphism in human saliva". Hum. Hered. 26 ...
"17 beta-hydroxysteroid dehydrogenase type XI localizes to human steroidogenic cells". Endocrinology. 144 (5): 2084-91. doi: ... "Entrez Gene: HSD17B11 hydroxysteroid (17-beta) dehydrogenase 11". Li KX, Smith RE, Krozowski ZS (1999). "Cloning and expression ... Estradiol 17-beta-dehydrogenase 11 is an enzyme that in humans is encoded by the HSD17B11 gene. GRCh38: Ensembl release 89: ... Haeseleer F, Palczewski K (2000). "Short-chain dehydrogenases/reductases in retina". Methods in Enzymology. 316: 372-83. doi: ...
... the type II 3 beta-hydroxysteroid dehydrogenase gene in a patient with classic salt-wasting 3 beta-hydroxysteroid dehydrogenase ... of type II 3 beta-hydroxysteroid dehydrogenase gene in Japanese patients with classical 3 beta-hydroxysteroid dehydrogenase ... 1992). "Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) gene: adrenal ... 1995). "A novel missense mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene in a family with classical salt- ...
Moghrabi N, Head JR, Andersson S (Nov 1997). "Cell type-specific expression of 17 beta-hydroxysteroid dehydrogenase type 2 in ... Oliveira IO, Lhullier C, Brum IS, Spritzer PM (Sep 2003). "Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in ... 17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) is an enzyme of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family that in ... "The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species". DNA and Cell ...
42 (1): 1-23. doi:10.1016/j.jchemneu.2011.05.003. PMC 3148274. PMID 21605659. Dong, HW; Petrovich, GD; Watts, AG; Swanson, LW ( ... 1115 (1): 54-64. doi:10.1016/j.brainres.2006.07.091. PMID 16935272. Geerling, JC; Kawata, M; Loewy, AD (Jan 20, 2006). " ... Geerling, JC; Engeland, WC; Kawata, M; Loewy, AD (Jan 11, 2006). "Aldosterone target neurons in the nucleus tractus solitarius ... Geerling, JC; Loewy, AD (Aug 1, 2006). "Aldosterone-sensitive neurons in the nucleus of the solitary tract: bidirectional ...
Studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue". Steroids. 62 (1): 77-82 ... 11α-OHP is a more potent inhibitor of 11β-HSD than enoxolone (glycyrrhetinic acid) or carbenoxolone in vitro (IC50 = 0.9 nM; ... 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 ... In 1995, 11α-OHP, along with its epimer 11β-hydroxyprogesterone, was identified as a very potent competitive inhibitor of both ...
... type 2 deficiency 17 alpha hydroxylase deficiency 17 beta hydroxysteroide dehydrogenase deficiency 17-beta-hydroxysteroid ... type 3, rare (NIH) 3 beta hydroxysteroid dehydrogenase deficiency 3 hydroxyisobutyric aciduria 3 methylcrotonic aciduria 3 ... Diseases Alphabetical list 0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z See also Health Exercise Nutrition 11 beta ... dehydrogenase deficiency, rare (NIH) 17q21.31 microdeletion syndrome 18-Hydroxylase deficiency, rare (NIH) 18p deletion ...
3(or+17)beta-hydroxysteroid+dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH) Biology portal ... Soubhye J, Alard IC, van Antwerpen P, Dufrasne F (2015). "Type 2 17-β hydroxysteroid dehydrogenase as a novel target for the ... Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in ... Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX (April 2010). "17beta-hydroxysteroid dehydrogenase type 1 stimulates breast ...
Rheault P, Dufort I, Soucy P, Luu-The V (1999). "Assignment of HSD17B5 encoding type 5 17 beta-hydroxysteroid dehydrogenase to ... 3-alpha hydroxysteroid dehydrogenase, type II)". Theisen, J. Graham; Sundaram, Viji; Filchak, Mary S.; Chorich, Lynn P.; ... also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is ... "Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5". Molecular and ...
... estradiols having inhibitory effect on human placental estradiol 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD type 1)". ... "Entrez Gene: HSD17B1 Hydroxysteroid (17-beta) dehydrogenase 1". Saloniemi T, Jokela H, Strauss L, Pakarinen P, Poutanen M (2012 ... Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX (Apr 2010). "17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer ... Sawetawan C, Milewich L, Word RA, Carr BR, Rainey WE (Mar 1994). "Compartmentalization of type I 17 beta-hydroxysteroid ...
Mindnich R, Möller G, Adamski J (2004). "The role of 17 beta-hydroxysteroid dehydrogenases". Mol. Cell. Endocrinol. 218 (1-2): ... Soubhye J, Alard IC, van Antwerpen P, Dufrasne F (2015). "Type 2 17-β hydroxysteroid dehydrogenase as a novel target for the ... 3(or+17)beta-hydroxysteroid+dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH) ... Talalay P, Dobson MM (December 1953). "Purification and properties of a beta-hydroxysteroid dehydrogenase". The Journal of ...
This type of receptor becomes activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly ... 1 (1). doi:10.15347/wjm/2014.005. ISSN 2002-4436. Omar, HR; Komarova, I; El-Ghonemi, M; Fathy, A; Rashad, R; Abdelmalak, HD; ... This enzyme, 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2), catalyzes the deactivation of glucocorticoids to ... 11 ed)., Saunders Elsevier, Philadelphia, pp. 445-504. Bennett PN and Brown MJ (2008) "Adrenal corticosteroids, antagonists, ...
"Polymorphism in exon 4 of the human 3 beta-hydroxysteroid dehydrogenase type I gene (HSD3B1) and blood pressure". Biochemical ... "Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the ... "Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in ... HSD3B1 is a human gene that encodes for a 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase type I or hydroxy-delta ...
Soubhye J, Alard IC, van Antwerpen P, Dufrasne F (2015). "Type 2 17-β hydroxysteroid dehydrogenase as a novel target for the ... Sam KM, Auger S, Luu-The V, Poirier D (1995). "Steroidal spiro-gamma-lactones that inhibit 17 beta-hydroxysteroid dehydrogenase ... Poirier D (2003). "Inhibitors of 17 beta-hydroxysteroid dehydrogenases". Curr. Med. Chem. 10 (6): 453-77. doi:10.2174/ ... "Spironolactone-related inhibitors of type II 17beta-hydroxysteroid dehydrogenase: chemical synthesis, receptor binding ...
"Abundant type 10 17 beta-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model". Brain Research. ... 17-β-Hydroxysteroid dehydrogenase X (HSD10) also known as 3-hydroxyacyl-CoA dehydrogenase type-2 is a mitochondrial enzyme that ... 17-beta) dehydrogenase 10". He XY, Yang YZ, Schulz H, Yang SY (Jan 2000). "Intrinsic alcohol dehydrogenase and hydroxysteroid ... Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (Sep 2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in ...
Dehydrogenase/reductase (SDR family) member 7B is an enzyme encoded by the DHRS7B gene in humans, found on chromosome 17p11.2. ... CD44 is an antigen found on the surface of most cell types and functions as a receptor that binds tissue macromolecules. ... "Entrez Gene: Dehydrogenase/reductase (SDR family) member 7B". "Genecards: DHRS7B Gene protein-coding GIFtS 47". Tannin GM, ... DHRS7B is a member of the short chain dehydrogenase/reductase (SDR) superfamily and possesses characteristic features of an SDR ...
XY disorder of sex development due to 17-beta hydroxysteroid dehydrogenase type 3 deficiency: a plea for timely genetic testing ... 11 (2): 95-97. doi:10.1007/BF03034401. Hughes I (2008). "The Testes: Disorders of Sexual Differentiation and Puberty in the ... 40 (1): 4075-4076. doi:10.1002/ajmg.1320400114. PMID 1909490. Nieschlag E, Behre H, Wieacker P, Meschede D, Kamischke A, ... doi:10.1016/B978-1-4160-4090-3.X5001-7. ISBN 9781416040903. PMC 1491552. "Gonadal Streak. Farlex Partner Medical Dictionary". ...
17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds". Steroids. 43 (3): 271-82. doi:10.1016/0039-128x(84) ... 27 (3 Pt 1): 421-5. doi:10.1161/01.hyp.27.3.421. PMID 8698448. Fürstenberger C, Vuorinen A, Da Cunha T, Kratschmar DV, Saugy M ... In accordance, 11α- and 11β-hydroxyprogesterone are known to be potent inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD ... ISBN 978-1-4757-2085-3. Felippone F, Resnati G, Scolastico C, Tronconi G (1984). "Synthesis of 2-carboxy-11 beta, ...
The 17-beta-hydroxysteroid dehydrogenase enzyme (EC 1.1.1.62) oxidizes or reduces estrogens and androgens in mammals and ... Ohnesorg T, Adamski J (2005). "Promoter analyses of human and mouse 17beta-hydroxysteroid dehydrogenase type 7". J. Steroid ... "Entrez Gene: HSD17B7 hydroxysteroid (17-beta) dehydrogenase 7". Mendoza-Hernández G, Rendón JL, Díaz-Zagoya JC (1985). "A ... "Two 17beta-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7". J Steroid Biochem Mol ...
"Human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase. Two activities at a single enzyme ... Akinola LA, Poutanen M, Vihko R, Vihko P (July 1997). "Expression of 17beta-hydroxysteroid dehydrogenase type 1 and type 2, ... Other names in common use include 20alpha-hydroxy steroid dehydrogenase, 20alpha-hydroxy steroid dehydrogenase, 20alpha-HSD, ... In enzymology, a 20-α-hydroxysteroid dehydrogenase (EC 1.1.1.149) is an enzyme that catalyzes the chemical reaction 17alpha, ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... a type 2 diabetic will have lost about half of their beta cells.[52] Fatty acids in the beta cells activate FOXO1, resulting in ... Xi B, Li S, Liu Z, Tian H, Yin X, Huai P, Tang W, Zhou D, Steffen LM (2014). "Intake of fruit juice and incidence of type 2 ... Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.[13] Insulin ...
Beta-Ketoacyl ACP reductase. *Carbohydrate dehydrogenases. *Carnitine dehydrogenase. *D-malate dehydrogenase (decarboxylating) ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ... This EC 1.1.1 enzyme-related article is a stub. You can help Wikipedia by expanding it.. *v ...
Beta-Ketoacyl ACP reductase. *Carbohydrate dehydrogenases. *Carnitine dehydrogenase. *D-malate dehydrogenase (decarboxylating) ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ... Other names in common use include 2-hydroxy-3-carboxyadipate dehydrogenase, 3-carboxy-2-hydroxyadipate dehydrogenase, ...
Beta-Ketoacyl ACP reductase. *Carbohydrate dehydrogenases. *Carnitine dehydrogenase. *D-malate dehydrogenase (decarboxylating) ... 2ikg: Aldose reductase complexed with nitrophenyl-oxadiazol type inhibitor at 1.43 A ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ... alcohol dehydrogenase (NADP+) activity. • retinal dehydrogenase activity. • allyl-alcohol dehydrogenase activity. • NADP- ...
"Autoimmune polyglandular syndrome type 1 , Genetic and Rare Diseases Information Center (GARD) - an NCATS Program". ... and beta-lipotropin. The subunit ACTH undergoes further cleavage to produce alpha-MSH, the most important MSH for skin ... "Autoimmune polyglandular syndrome type 2 , Genetic and Rare Diseases Information Center (GARD) - an NCATS Program". ... Addison's disease is associated with the development of other autoimmune diseases, such as type I diabetes, thyroid disease ( ...
... either lactate dehydrogenase-A deficiency (also known as glycogen storage disease XI) or lactate dehydrogenase-B deficiency. ... The N-terminus is a Rossmann NAD-binding fold and the C-terminus is an unusual alpha+beta fold.[5][6] ... Expression of LDH5 and VEGF in tumors and the stroma has been found to be a strong prognostic factor for diffuse or mixed-type ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ...
Pyruvate dehydrogenase deficiency. *Danon disease/glycogen storage disease Type IIb. *Lipid storage disorder: Fabry's disease ... 17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... There are four types of DI, each with a different set of causes.[1] Central DI (CDI) is due to a lack of the hormone ... Carbamazepine, an anticonvulsive medication, has also had some success in this type of DI. Also, gestational DI tends to abate ...
Type A (express A antigens), Type B (express B antigens), Type AB (express both A and B antigens) and Type O (express neither A ... Herbst EA, MacPherson RE, LeBlanc PJ, Roy BD, Jeoung NH, Harris RA, Peters SJ (Jan 2014). "Pyruvate dehydrogenase kinase-4 ... Due to this, alcohol sulfotransferase is also known by several other names including "hydroxysteroid sulfotransferase," " ... Earliest discoveries of transferase activity occurred in other classifications of enzymes, including Beta-galactosidase, ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... beginning immediately after a diagnosis of type 2 diabetes and five years after a diagnosis of type 1 diabetes.[24][27] Medical ... The prevalence of type 2 DM is particularly increasing due to the rising prevalence of obesity worldwide.[49] Diabetic kidney ... "Effects of Intensive Glucose Lowering in Type 2 Diabetes". New England Journal of Medicine. 358 (24): 2545-2559. 2008-06-12. ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... It was previously thought that particular types of pituitary tumors were more prone to apoplexy than others, but this has not ... 1: 789-92.. *^ a b Russell SJ, Klahr Miller K (2008). "Pituitary apoplexy". In Swearingen B, Biller BM. Diagnosis and ... ISBN 978-1-58829-922-2.. *^ Thorner MO, Vance ML, Horvath E, Kovacs K (1992). "The anterior pituitary". In Wilson JD, Foster DW ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... Types[edit]. Name. OMIM. Description. Seckel syndrome. 210600. People with Seckel syndrome are noted to have microcephaly. Many ... Osteodysplastic Primordial Dwarfism, Type II (MODPD2). 210720. Those who have ODPDII often have additional medical problems as ... The five subtypes of primordial dwarfism are among the most severe forms of the 200 types of dwarfism, and some sources ...
Beta-Ketoacyl ACP reductase. *Carbohydrate dehydrogenases. *Carnitine dehydrogenase. *D-malate dehydrogenase (decarboxylating) ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ... In enzymology, a carnitine 3-dehydrogenase (EC 1.1.1.108) is an enzyme that catalyzes the chemical reaction ...
16α-OH-DHEA is converted by 3β-hydroxysteroid dehydrogenase type I (3β-HSD1) into 16α-hydroxyandrostenedione (16α-OH-A4) and 16 ... "Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta". Biochemical ... DHEA is converted by 3β-hydroxysteroid dehydrogenase type I into androstenedione, and androstenedione is aromatized into ... which is subsequently converted into estriol by 17β-hydroxysteroid dehydrogenase and then secreted predominantly into the ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... Pluripotent stem cells can be used to generate beta cells but previously these cells did not function as well as normal beta ... This distinguishes type 1's origin from type 2. Type 2 diabetes is characterized by insulin resistance, while type 1 diabetes ... "Nutritional risk predictors of beta cell autoimmunity and type 1 diabetes at a young age". The American Journal of Clinical ...
Beta-Ketoacyl ACP reductase. *Carbohydrate dehydrogenases. *Carnitine dehydrogenase. *D-malate dehydrogenase (decarboxylating) ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ... beta-ketoacyl acyl carrier protein (ACP) reductase, beta-ketoacyl reductase, beta-ketoacyl thioester reductase, beta-ketoacyl- ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ...
... which is subsequently converted to estradiol via 17β-hydroxysteroid dehydrogenase (17β-HSD).[46] ... Collins P, Rosano GM, Sarrel PM, Ulrich L, Adamopoulos S, Beale CM, McNeill JG, Poole-Wilson PA (July 1995). "17 beta-Estradiol ... and estrus-type changes (including vaginal, uterine, and mammary gland changes and sexual receptivity) in sexually immature, ... 345-. ISBN 978-1-119-20246-2.. *^ a b c d e f g h i Lauritzen C, Studd JW (22 June 2005). Current Management of the Menopause. ...
Beta-Ketoacyl ACP reductase. *Carbohydrate dehydrogenases. *Carnitine dehydrogenase. *D-malate dehydrogenase (decarboxylating) ... As GLUT transporters and stomatin are ubiquitously distributed in different human cell types and tissues, similar interactions ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ... 7 (1).. *^ Gombart AF (November 2009). "The vitamin D-antimicrobial peptide pathway and its role in protection against ...
This type of receptor becomes activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly ... Steroidogenesis, showing mineralocorticoids in ellipse at top right.[1] Note that it is not a strictly bounded group, but a ... This enzyme, 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2), catalyzes the deactivation of glucocorticoids to ... Stewart P (2008): "The Adrenal Cortex " In: Kronenberg, Melmed, Polonsky, Larsen (eds.) Williams Textbook of Endocrinology (11 ...
Hydroxysteroid dehydrogenase. ... "reverse type I" spectrum, by processes that are as yet unclear ... This can be measured by difference spectrometry and is referred to as the "type I" difference spectrum (see inset graph in ... Inhibitors and certain substrates that bind directly to the heme iron give rise to the type II difference spectrum, with a ... Retrieved 2014-11-13.. *^ Hanukoglu, Israel (1996). Electron Transfer Proteins of Cytochrome P450 Systems (PDF). Advances in ...
... or 17-beta-hydroxysteroid dehydrogenase deficiency (17beta-HSD-3).[8][9] A relative handful of male to female changes have been ... This cooling will produce a chicken with a fully functioning and reproductively fertile female body-type; even though the ... XY Persons with 5α-Reductase-2 Deficiency and 17β-Hydroxysteroid Dehydrogenase-3 Deficiency". Archives of Sexual Behavior. 34 ( ... "17β-Hydroxysteroid dehydrogenase-3 deficiency: A rare endocrine cause of male-to-female sex reversal". Gynecological ...
... and oxidative 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase enzymes.[42] ... 2010). "Human type 3 5α- reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is ... "Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently ... specifically with local expression at the skin of reductive 17β-hydroxysteroid dehydrogenase, ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... type 2, gestational diabetes, and "other specific types".[8] The "other specific types" are a collection of a few dozen ... Mechanism of insulin release in normal pancreatic beta cells. Insulin production is more or less constant within the beta cells ... This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated ...
Enzymes involved in this process include both mitochondrial and microsomal P450s and hydroxysteroid dehydrogenases. Usually a ... The adrenal glands are composed of two heterogenous types of tissue. In the center is the adrenal medulla, which produces ... A complication seen in untreated Addison's disease and other types of primary adrenal insufficiency is the adrenal crisis, a ... The central adrenomedullary vein, in the adrenal medulla, is an unusual type of blood vessel. Its structure is different from ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... Other types may not stimulate the thyroid gland, but prevent TSI and TSH from binding to and stimulating the receptor. ... The rationale for radioactive iodine is that it accumulates in the thyroid and irradiates the gland with its beta and gamma ... The three types of autoantibodies to the TSH receptor currently recognized are: *Thyroid stimulating immunoglobulins: these ...
3-beta-HSD. References[edit]. *^ Wikvall K (April 1981). "Purification and properties of a 3 β-hydroxy-delta 5-C27-steroid ... Phosphogluconate dehydrogenase. *Sorbitol dehydrogenase. *Hydroxysteroid dehydrogenase: 3β *3β-HSD. *NSDHL ... Types. *EC1 Oxidoreductases (list). *EC2 Transferases (list). *EC3 Hydrolases (list). *EC4 Lyases (list) ... In enzymology, a cholest-5-ene-3β,7α-diol 3β-dehydrogenase (EC 1.1.1.181) is an enzyme that catalyzes the chemical reaction[1] ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... Types of disease[edit]. Broadly speaking, endocrine disorders may be subdivided into three groups:[1] ... Male left, female on the right.) 1. Pineal gland 2. Pituitary gland 3. Thyroid gland 4. Thymus 5. Adrenal gland 6. Pancreas 7. ... Savage, M W; P Mah; A Weetman; J Newell-Price (1 September 2004). "Endocrine emergencies". Postgraduate Medical Journal. 80 ( ...
11Beta-hydroxysteroid dehydrogenase type 1 in human disease: a novel therapeutic target.. Tomlinson JW1. ... At a tissue specific level, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally regenerates active ... Publication type, MeSH terms, Substances. Publication type. *Review. MeSH terms. *11-beta-Hydroxysteroid Dehydrogenase Type 1/ ... Here we review the role of 11beta-HSD1 in human disease and discuss the impact of selective 11beta-HSD1 inhibition. ...
Human 11beta-Hydroxysteroid Dehydrogenase Type 1 in complex with AZD8329. *DOI: 10.2210/pdb4P38/pdb ... Corticosteroid 11-beta-dehydrogenase isozyme 1. A, B. 265. Homo sapiens. Mutation(s): 0 Gene Names: HSD11B1, HSD11, HSD11L, ... 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid. C25 H31 N3 O3. XWBXJBSVYVJAMZ-RCQAVAAASA-N. Ligand ... Inhibition of 11β-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic ...
Resource Type:. Journal Article. Resource Relation:. Journal Name: Acta Crystallogr. F; Journal Volume: 68; Journal Issue: (5 ... Qin, Wenying ; Judge, Russell A. ; Longenecker, Kenton L. ; Solomon, Larry R. ; Harlan, John E. [1] + Show Author Affiliations ... beta]-hydroxysteroid dehydrogenase type 1 ... a case study with human 11[beta]-hydroxysteroid dehydrogenase ... Title: On-column ligand exchange for structure-based drug design: a case study with human 11[ ...
Although elevated activity of the glucocorticoid-amplifying enzyme 11beta-hydroxysteroid dehydrogenase … ... Preadipocyte 11beta-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in ... Although elevated activity of the glucocorticoid-amplifying enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) ... 11beta-HSD1 mRNA and protein levels were comparable between ASV and adipocyte fractions in both depots. 11beta-HSD1 was an ...
... is developing 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors for the ... Research Type 2 diabetes mellitus Most Recent Events * 21 Oct 2016 11-beta hydroxysteroid dehydrogenase type 1 inhibitors are ... 16 Jul 2016 No recent reports of development identified for research development in Type-2-diabetes-mellitus in France ... 28 May 2009 Early research in Type-2 diabetes mellitus in France (unspecified route) ...
... beta-cell dysfunction and increased endogenous glucose production. Glucocorticoids have received considerable interest among ... 11beta-hydroxysteroid dehydrogenase type 1 as a pharmacological target in metabolic disease. Author: Hult, Malin ... The enzyme responsible for this conversion of glucocorticoids is 11beta-hydroxysteroid dehydrogenase (11beta-HSD). Two ... A novel role of 11beta-HSD1 in 7-oxosterol metabolism was discovered and investigated using recombinant 11beta-HSD1 orthologs. ...
... ... 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. 2009, 58 (11 ... 11beta-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets. ... Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone ...
Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone ... A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer(307) IRS1 and reduction in ... Selective 11beta-HSD1 inhibition decreases pSer(307) IRS1, increases pThr(308) Akt/PKB, and decreases lipogenic and lipolytic ... In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin ...
11-Beta-Hydroxysteroid Dehydrogenase Type 1 (Hsd11b1) Antibody 由Abbexa供应,该产品简介:11-Beta-Hydroxysteroid Dehydrogenase Type 1 ( ... 注:1.可以使用快捷键Alt+S或Ctrl+Enter发送信息!. 2.如有必要,请您留下您的详细联系方式! ... 产品名称:11-Beta-Hydroxysteroid Dehydrogenase Type 1 (Hsd11b1) Antibody ... 地址:上海市闵
Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, ... carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). In this study, we determined the role of glucocorticoid ... Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. The presence of 11beta-HSD in islets ... Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob ...
Human ALDH1A2(Aldehyde Dehydrogenase 1 Family, Member A2) ELISA Kit. *Human ALDOC(Aldolase C, Fructose Bisphosphate) ELISA Kit ... Human PCSK5(Proprotein Convertase Subtilisin/Kexin Type 5) ELISA Kit. *Human PDGFC(Platelet Derived Growth Factor C) ELISA Kit ... Human ALDH1A1(Aldehyde Dehydrogenase 1 Family, Member A1) ELISA Kit. * ... Human CELSR2(Cadherin EGF LAG Seven Pass G-Type Receptor 2) ELISA Kit ...
11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid ... 11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type ... We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. The enzyme, either as full- ... Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical ...
Cortisol Metabolism and Hepatic Expression of 11 beta-Hydroxysteroid Dehydrogenase Type 1 in Patients with Non Alcoholic Fatty ... Cortisol Metabolism and Hepatic Expression of 11 beta-Hydroxysteroid Dehydrogenase Type 1 in Patients with Non Alcoholic Fatty ...
The latter effect is accomplished by two different 11beta-hydroxysteroid dehydrogenase isozymes, constituting a shuttle system ... The type 2 enzyme is an exclusive NAD+ dependent dehydrogenase of glucocorticoids, thus protecting the mineralocorticoid ... Whereas the type 1 enzyme (11beta-HSD1) is in vitro a NADP(H)- dependent bidirectional enzyme, it reduces in most instances in ... Importantly, 11beta-HSD1 activity appears to be intrinsically linked to all features of the metabolic syndrome, which could at ...
Heterologous production of 11beta-HSD1, devoid of its N-terminal transmembrane segment, is possible but yields only small ... Here we show that the soluble portion of recombinant 11beta-HSD1 produced in E. coli is found mainly as multimeric aggregates ... Moreover, active site titration of human 11beta-HSD1 revealed that at least 75% of the protein in a typical preparation ... By co-overexpressing GroEL/ES and adding an 11beta-HSD1 inhibitor during protein synthesis, we have increased the accumulation ...
... by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) has been postulated as a pathogenic mechanism. Although levels of ... Weight loss increases 11beta-hydroxysteroid dehydrogenase type 1 expression in human adipose tissue. ... Weight loss increases 11beta-hydroxysteroid dehydrogenase type 1 expression in human adipose tissue. ... Weight loss increases 11beta-hydroxysteroid dehydrogenase type 1 expression in human adipose tissue. ...
11beta-HSD1) have considerable potential as treatments for metabolic diseases, such as diabetes mellitus type 2 or obesity. ... inhibition for 11beta-HSD1 at 10 microM and exhibited IC50 values in the low micromolar range. The preliminary SAR study ... the discovery and synthesis of a series of novel benzothiazole derivatives and their inhibitory activities against 11beta-HSD1 ... Docking studies with the benzothiazole derivative 1 into the crystal structure of human 11beta-HSD1 revealed how the molecule ...
Recently, the SDR enzyme 11beta-hydroxysteroid dehydrogenase-1 has been identified to perform an important role in the ... This reaction is mediated by members of the aldo-keto reductase and short-chain dehydrogenase/reductase (SDR) superfamilies. ... This review summarises the current knowledge of type-1 11beta-hydroxysteroid dehydrogenase and discusses possible substrate/ ... Recently, the SDR enzyme 11beta-hydroxysteroid dehydrogenase-1 has been identified to perform an important role in the ...
Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102-110pmid:12502499. ... 11Beta-hydroxysteroid dehydrogenase type 1 and obesity. Front Horm Res 2008;36:146-164pmid:18230901. ... 11Beta-hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets. Diabetologia 2008;51: ... Preadipocyte 11beta-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in ...
Their findings showed that the D-bifunctional protein plays an essential role in the peroxisomal beta-oxidation pathway that ... Biochemical analysis showed that the 3-hydroxyacyl-CoA dehydrogenase activity of the D-bifunctional protein was completely ... 11 beta hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Media:. ... 11 beta hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. In 2 unrelated patients, Ulick et ...
Rat 11-Beta-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) ELISA Kit Abbexa Ltd ...
Recombinant soluble proteins were expressed and purified with high specific dehydrogenase and reductase activities, revealing ... Type 1 11 beta-hydroxysteroid dehydrogenase constitutes a prereceptor control mechanism through its ability to reduce ... Instead, the expression of 11 beta-hydroxysteroid dehydrogenase type 1 in the Zona glomerulosa of the guinea pig adrenal gland ... The kinetic data obtained argue against the involvement of 11 beta-hydroxysteroid dehydrogenase as a modulating factor for the ...
The overall structure of guinea pig 11beta-HSD1 shows a clear relationship to other members of the superfamily of short-chain ... Here we report the crystal structure of recombinant guinea pig 11beta-HSD1. This variant was determined in complex with NADP at ... This reaction is carried out by the NADPH-dependent type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), an enzyme ... dehydrogenases/reductases but harbors a unique C-terminal helical segment that fulfills three essential functions and ...
Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes ... Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent ... frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 ... Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ...
Ovarian modulators of type 1 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activity and intra-follicular cortisol : ... Ovarian modulators of type 1 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activity and intra-follicular cortisol : ...
Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with ... impaired regeneration of active cortisol from inert cortisone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) results in ... Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ... 11beta-HSD1 deficiency may protect against obesity and its metabolic consequences because of impaired regeneration of cortisol ...
Elevenbeta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), a key intracellular enzyme which catalyses the conversion of ... If confirmed, these results would prompt the development of selective and tissue-specific 11beta-HSD-1 inhibitors to decrease ... 11β-hydroxysteroid dehydrogenase type 1; Cortisol; Cortisone; Metabolic syndrome. Settore Scientifico Disciplinare: Settore MED ... are less convincing with several case control and cross-sectional studies showing an association between with 11beta-HSD-1 ...
Altered endogenous glucocorticoid metabolism, including 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which ... Two women and five men were diagnosed with type 2 diabetes. In women, adipose 11beta-HSD1 expression was increased in patients ... Increased adipose 11beta-HSD1 expression in women may contribute to glucose intolerance. Enhanced 5alphaR activity in both ... Altered endogenous glucocorticoid metabolism, including 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which ...
Regulation of glucocorticoid receptor alpha and beta isoforms and type I 11beta-hydroxysteroid dehydrogenase expression in ... 11Beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 2004;25:831-866 ... 11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. J Clin Endocrinol ... Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in ...
1,,img id=EMI-C00001 he=54.36mm wi=65.28mm file=US20070207984A1-20070906-C000 ... Previous Patent: Use of Sphingolipids in the Treatment and Prevention of Type 2 Diabetes Mellitus, Insulin Resistance.... Next ... Preferably topical administration will be accomplished using a patch either of the reservoir and porous membrane type or of a ... wherein Q1, Q2, RN, R1, R2, R5, R6, R7, R8, X1, X2, X4, and Y are as defined herein. Compounds of Formula (I) are useful in the ...
  • human omental adipose stromal vascular (ASV) cells exhibit 11beta-dehydrogenase activity (inactivation of glucocorticoids) probably due to the absence of cofactor provision by hexose-6-phosphate dehydrogenase. (nih.gov)
  • 11beta-HSD1 was an 11beta-reductase, thus reactivating glucocorticoids in ASV cells, consistent with hexose-6-phosphate dehydrogenase mRNA expression. (nih.gov)
  • Mutations in this gene and H6PD (hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)) are the cause of cortisone reductase deficiency. (genecards.org)
  • The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). (medworm.com)
  • An important gene associated with Hyperandrogenism Due to Cortisone Reductase Deficiency is H6PD (Hexose-6-Phosphate Dehydrogenase/Glucose 1-Dehydrogenase). (malacards.org)
  • Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. (malacards.org)
  • The enzyme responsible for this conversion of glucocorticoids is 11beta-hydroxysteroid dehydrogenase (11beta-HSD). (ki.se)
  • Regulation of lipid metabolism by glucocorticoids and 11β-HSD1 in skeletal muscle. (lenus.ie)
  • Glucocorticoids and 11β-HSD1 are major regulators of intramyocellular protein metabolism. (lenus.ie)
  • RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. (ox.ac.uk)
  • Their effects primarily depend on their binding to intracellular receptors leading to altered target gene transcription as well as on cell-type specific biotransformation between 11beta-hydroxy glucocorticoids and their 11-oxo metabolites. (ox.ac.uk)
  • The type 2 enzyme is an exclusive NAD+ dependent dehydrogenase of glucocorticoids, thus "protecting" the mineralocorticoid receptor against illicit occupation by cortisol. (ox.ac.uk)
  • Animal studies and pharmacological experiments suggest further unrelated target areas, for example improvement of cognitive function and treatment of glaucoma, due to the role of glucocorticoids and cellular activation by 11beta-HSD1 in these pathologies. (ox.ac.uk)
  • Abnormally elevated intracellular regeneration of glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in fat or liver may underlie pathophysiological aspects of the metabolic syndrome. (diabetesjournals.org)
  • 11β-HSD1 is elevated in islets of diabetic rodents ( 4 - 6 ), where it was hypothesized to promote β-cell failure by amplifying the suppressive effects of glucocorticoids on insulin secretion ( 7 , 8 ). (diabetesjournals.org)
  • Estimates suggest that 1-2% of the population of the United States and United Kingdom take prescribed glucocorticoids (GCs) for the treatment of a broad spectrum of inflammatory and autoimmune diseases ( 1 , 2 ). (pnas.org)
  • Excess glucocorticoids , a type of steroid that may be administered as a drug. (healthengine.com.au)
  • SHARP, V., THURSTON, L. M., FOWKES, R. C. & MICHAEL, A. E. (2007) 11Beta-hydroxysteroid dehydrogenase enzymes in the testis and male reproductive tract of the boar (Sus scrofa domestica) indicate local roles for glucocorticoids in male reproductive physiology. (rvc.ac.uk)
  • Objectives The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a well-characterised role in the metabolism and activation of endogenous glucocorticoids (GCs). (bmj.com)
  • Enzymes such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which is potently upregulated at sites of inflammation, reactivates inactive glucocorticoids such as prednisone. (bmj.com)
  • At a tissue specific level, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally regenerates active cortisol from inactive cortisone amplifying glucocorticoid receptor activation in the context of normal circulating cortisol levels. (nih.gov)
  • Unexpectedly, glucocorticoid reactivation was higher in intact mesenteric ASV cells despite a lower expression of 11beta-HSD1 mRNA and protein (homogenate activity) levels than sc ASV cells. (nih.gov)
  • 11beta-HSD1 mediates activation of the glucocorticoid precursor cortisone (in humans) to the active glucocorticoid receptor ligand cortisol. (ki.se)
  • Because of the beneficial effects of reduced tissue glucocorticoid levels in the metabolic syndrome and related disorders, 11beta-HSD1 is a pursued target of pharmacological intervention. (ki.se)
  • 11beta-HSD1 mediates glucocorticoid-activation in pancreatic islets of Langerhans, and thereby regulates glucose-stimulated insulin secretion. (ki.se)
  • 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. (lenus.ie)
  • We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity. (lenus.ie)
  • 11β-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue. (lenus.ie)
  • Skeletal muscle 11beta-HSD1 controls glucocorticoid-induced proteolysis and expression of E3 ubiquitin ligases atrogin-1 and MuRF-1. (lenus.ie)
  • CONCLUSIONS: Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer(307) IRS1 and may be crucial in mediating insulin resistance in skeletal muscle. (ox.ac.uk)
  • Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. (ox.ac.uk)
  • In this study, we determined the role of glucocorticoid conversion by 11beta-HSD in pancreatic islets and its function in the regulation of insulin release. (ox.ac.uk)
  • The presence of 11beta-HSD in islets supports the concept that reactivation of inert circulating hormone precursors in a cell-specific manner plays a major role in glucocorticoid physiology in rodents and man. (ox.ac.uk)
  • Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. (ox.ac.uk)
  • Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. (ox.ac.uk)
  • Inhibition of tissue-specific glucocorticoid activation by 11beta-HSD1 constitutes a promising target in the treatment of metabolic and cardiovascular diseases. (ox.ac.uk)
  • The recent development of specific 11beta-HSD1 inhibitors coupled with advances on structural knowledge and regulation of the 11beta-HSD1 target has undoubtedly promoted the understanding of glucocorticoid control of metabolic regulation. (ox.ac.uk)
  • Recently, the SDR enzyme 11beta-hydroxysteroid dehydrogenase-1 has been identified to perform an important role in the detoxification of non-steroidal carbonyl compounds, in addition to metabolising its physiological glucocorticoid substrates. (ox.ac.uk)
  • Comparative enzymology of 11 beta -hydroxysteroid dehydrogenase type 1 from glucocorticoid resistant (Guinea pig) versus sensitive (human) species. (ox.ac.uk)
  • We compared kinetic characteristics of the human and guinea pig 11 beta-hydroxysteroid dehydrogenase isozymes derived from species differing in glucocorticoid sensitivity. (ox.ac.uk)
  • The kinetic data obtained argue against the involvement of 11 beta-hydroxysteroid dehydrogenase as a modulating factor for the glucocorticoid resistance observed in guinea pigs. (ox.ac.uk)
  • The metabolic reduction of 11-keto groups in glucocorticoid steroids such as cortisone leads to the nuclear receptor ligand cortisol. (ox.ac.uk)
  • If confirmed, these results would prompt the development of selective and tissue-specific 11beta-HSD-1 inhibitors to decrease insulin resistance and treat the metabolic syndrome, thus contrasting the harmful effects of glucocorticoid excess in peripheral tissues. (unimi.it)
  • Altered endogenous glucocorticoid metabolism, including 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which generates active cortisol from cortisone, and 5alpha-reductase (5alphaR), which inactivates cortisol, has been implicated. (ox.ac.uk)
  • Elevated local tissue glucocorticoid excess, driven by increased levels of the intracellular glucocorticoid regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), particularly in adipose tissue, is implicated in the development of idiopathic metabolic syndrome ( 3 ). (diabetesjournals.org)
  • OBJECTIVE The cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. (diabetesjournals.org)
  • Here we present data to demonstrate that the adverse side-effect profile associated with exogenous active glucocorticoid (GC) administration (including glucose intolerance, hyperinsulinemia, hypertension, hepatic steatosis, increased adiposity, and myopathy) is prevented by global deletion of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in mice. (pnas.org)
  • The enzyme 11β-HSD1 is widely expressed and yields increased local tissue concentration of active glucocorticoid by converting cortisone into cortisol in humans, and 11-dehydrocorticosterone into corticosterone in rodents. (axonmedchem.com)
  • In contrast, the enzyme 11β-HSD2 catalyzes the opposite reaction, the inactivation of active glucocorticoid. (axonmedchem.com)
  • Glucocorticoid excess as a result of Cushing's syndrome or pharmacological treatment can result in the development of obesity and type 2 diabetes mellitus (T2DM). (ed.ac.uk)
  • The enzymatic origin of endogenous 7beta-OH-cholesterol in humans is assigned to 11beta- HSD1, possibly pointing to an involvement in atherosclerosis. (ki.se)
  • 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. (ox.ac.uk)
  • In humans, 11β-HSD1 also may be important to metabolic health, and selective 11β-HSD1 inhibitors are in development ( 11 ). (diabetesjournals.org)
  • Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the HSD11B2 gene. (wikipedia.org)
  • We previously showed that carbenoxolone, an old drug that blocks multiple enzymes including 11beta-HSD1, improves memory in healthy elderly men and in patients with type 2 diabetes after just a month of treatment, so we are optimistic that our new compounds will be effective in humans. (qualitycounts.com)
  • We measured fat content by dual-energy X-ray absorptiometry and magnetic resonance imaging (MRI), liver fat by ultrasound and MRI, the hypothalamic-pituitary-adrenal axis by adrenal response to ACTH 1-24 , unconjugated urinary cortisol excretion, corticosteroid-binding globulin, and cortisol clearance by MS. We assessed insulin sensitivity by hyperinsulinaemic-euglycaemic clamp and by OGTT. (springer.com)
  • Corticosteroid 11-β-dehydrogenase isozyme 2 is an NAD+-dependent enzyme expressed in aldosterone-selective epithelial tissues such as the kidney, colon, salivary and sweat glands. (wikipedia.org)
  • 11beta-hydroxysteroid dehydrogenase, corticosteroid 11β-dehydrogenase, β-hydroxysteroid dehydrogenase, 11β-hydroxy steroid dehydrogenase, corticosteroid 11-reductase, dehydrogenase, 11β-hydroxy steroid, 11β-hydroxysteroid:NADP+ 11-oxidoreductase, 11betaHSD, EC 1.1.1.146 ) adalah enzim dengan 2 isoform yang masing-masing mempercepat reaksi inter-konversi antara hormon kortisol dan hormon kortison . (wikipedia.org)
  • Should the Rat 11-Beta-Hydroxysteroid Dehydrogenase Type 1 (HSD11b1) ELISA Kit is proven to show malperformance, you will receive a refund or a free replacement. (gentaur.se)
  • Description: A sandwich quantitative ELISA assay kit for detection of Rat 11-Beta-Hydroxysteroid Dehydrogenase Type 1 (HSD11b1) in samples from tissue homogenates, cell lysates or other biological fluids. (gentaur.se)
  • Your search returned 1 HSD11B1 ELISA ELISA Kit across 1 supplier. (biocompare.com)
  • HSD11B1 (Hydroxysteroid 11-Beta Dehydrogenase 1) is a Protein Coding gene. (genecards.org)
  • Two different isozymes of 11beta-HSD (11beta-HSD1 and 11beta-HSD2) are described. (ki.se)
  • The latter effect is accomplished by two different 11beta-hydroxysteroid dehydrogenase isozymes, constituting a shuttle system between the receptor ligand cortisol and its non-binding precursor cortisone. (ox.ac.uk)
  • 11beta-Hydroxysteroid Dehydrogenases (11beta-HSD) isozymes 11beta-HSD1 and 11beta-HSD2 catalyze the interconversion of cortisol and cortisone. (genecards.org)
  • Increased 11beta-HSD1 activity and expression have been implicated in the pathogenesis of many common conditions including, obesity, insulin resistance, the metabolic syndrome, polycystic ovarian syndrome, osteoporosis and glaucoma. (nih.gov)
  • The connection between insulin resistance and diabetes mellitus type 2 has been well established, and the major abnormalities are peripheral insulin resistance, beta-cell dysfunction and increased endogenous glucose production. (ki.se)
  • Impaired glucose tolerance and insulin resistance are associated with increased adipose 11beta-hydroxysteroid dehydrogenase type 1 expression and elevated hepatic 5alpha-reductase activity. (ox.ac.uk)
  • OBJECTIVE: The precise molecular mechanisms contributing to the development of insulin resistance, impaired glucose tolerance (IGT), and type 2 diabetes are largely unknown. (ox.ac.uk)
  • For example, transgenic mice selectively overexpressing 11β-HSD1 in adipose tissue develop obesity, insulin resistance, hypertension, and dyslipidemia ( 3 , 4 ). (diabetesjournals.org)
  • Several studies show that indices of hypothalamic-pituitary-adrenal (HPA) axis activity, including raised fasting cortisol concentrations and an increased adrenal response to ACTH 1-24 , are associated with insulin resistance independently of the effects of obesity [ 6 , 7 ], suggesting that patterns of cortisol metabolism vary according to insulin sensitivity. (springer.com)
  • In addition, ∼30% of patients who have insulin resistance eventually develop type 2 diabetes. (physiology.org)
  • Cortisol acts as an antagonist of insulin action, and 11beta-HSD1 mediated production of cortisol has been hypothesized to contribute to human insulin resistance and type 2 diabetes. (drugbank.ca)
  • Abdominal obesity has been strongly correlated with insulin resistance and type 2 diabetes, and cortisol may be involved (Franco, 2001). (kon.org)
  • GlobalData believes that in order to address the biggest unmet need in type 2 diabetes, new drugs must address the problem of insulin resistance, as this is the root of the disease. (drug-dev.com)
  • Cortisol is also produced from cortisone in peripheral adipose tissue by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (HSD 1), suggesting another potential point of dysregulation that may contribute to central obesity and insulin resistance in PCOS. (clinicaltrials.gov)
  • This is partly attributable to co-morbidities and risk factors such as type 2 diabetes, insulin resistance, hypertension, and dyslipidemias. (nih.gov)
  • Insulin resistance may be associated with stroke risk - Science Daily, 10/11/10 - 'Individuals in the top quarter of insulin resistance had a 45 percent greater risk of any type of vascular event. (qualitycounts.com)
  • Furthermore, selective 11beta-HSD1 inhibition has been proposed as a novel therapeutic strategy in many of these conditions. (nih.gov)
  • Here we review the role of 11beta-HSD1 in human disease and discuss the impact of selective 11beta-HSD1 inhibition. (nih.gov)
  • Inhibition of 11β-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic syndrome. (rcsb.org)
  • Hence it is postulated that the known beneficial effects of 11beta-HSD1-inhibition in the pharmacological treatment of diabetes mellitus can be extended to include improved insulin release in diabetic mice. (ki.se)
  • 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. (ox.ac.uk)
  • Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, indicating cellular activation of 11-dehydrocorticosterone to the receptor ligand, further confirmed by reporter gene assays. (ox.ac.uk)
  • Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. (ox.ac.uk)
  • The benzothiazole derivatives 1 and 2 showed greater than 80% inhibition for 11beta-HSD1 at 10 microM and exhibited IC50 values in the low micromolar range. (ox.ac.uk)
  • The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. (diabetesjournals.org)
  • These data challenge our current view of GC action, demonstrating 11β-HSD1, particularly in adipose tissue, is key to the development of the adverse metabolic profile associated with circulating GC excess, offering 11β-HSD1 inhibition as a previously unidentified approach to treat Cushing syndrome. (pnas.org)
  • Therefore, the inhibition of 11β-HSD1 is currently regarded as a promising therapeutic target [ 5 ]. (mdpi.com)
  • For example, GCs potently inhibit the production of proinflammatory cytokines, such as TNFα, presumably through the inhibition of the transcription factors NFκB and AP-1 ( 7 ). (rupress.org)
  • Acute inhibition of 11beta-hydroxysteroid dehydrogenase type-1 improves memory in rodent models of cognition. (discoverx.com)
  • Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. (axonmedchem.com)
  • 11beta-HSD1 orthologs from human, rat, mouse and guinea pig show considerable inter-species variations as inferred by primary structure determinations and inhibitor characterization. (ki.se)
  • A 11beta-HSD1 selective arylsulfonamidothiazole inhibitor class was investigated and is currently developed as a promising tool for the treatment of insulinresistance. (ki.se)
  • A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer(307) IRS1 and reduction in total IRS1 protein after treatment with 11DHC but not corticosterone. (ox.ac.uk)
  • In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin sensitivity. (ox.ac.uk)
  • By co-overexpressing GroEL/ES and adding an 11beta-HSD1 inhibitor during protein synthesis, we have increased the accumulation of soluble 11beta-HSD1 by more than one order of magnitude. (ox.ac.uk)
  • This review summarises the current knowledge of type-1 11beta-hydroxysteroid dehydrogenase and discusses possible substrate/inhibitor interactions. (ox.ac.uk)
  • It is an orally available small molecule inhibitor of 11beta-HSD1 (11-beta hydroxysteroid dehydrogenase type 1). (drugbank.ca)
  • In this paper, we examined the metabolic implications of curcumin, a compound known for its anti-inflammatory properties and inhibitory action on the enzyme 11β-HSD1, in a rodent model of adiposity rebound after the cessation of diet and exercise. (nih.gov)
  • Cortisol levels in these tissues are amplified by the 11β-reductase activity of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which regenerates cortisol from inert cortisone ( 2 ). (diabetesjournals.org)
  • The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is selectively expressed in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor. (ahajournals.org)
  • The GC-activating enzyme 11-beta hydroxysteroid dehydrogenase type 1 (11β-HSD1) displays increased activity in bone cells from older vs. younger donors. (bham.ac.uk)
  • The overall structure of guinea pig 11beta-HSD1 shows a clear relationship to other members of the superfamily of short-chain dehydrogenases/reductases but harbors a unique C-terminal helical segment that fulfills three essential functions and accordingly is involved in subunit interactions, contributes to active site architecture, and is necessary for lipid-membrane interactions. (ox.ac.uk)
  • It belongs to the family of short-chain dehydrogenases. (wikipedia.org)
  • Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 1) catalyzes the final step in the synthesis of active estrogens that stimulate the proliferation of breast cancer cells. (rcsb.org)
  • Androgen metabolism via 17beta-hydroxysteroid dehydrogenase type 3 in mammalian and non-mammalian vertebrates: comparison of the human and the zebrafish enzyme. (wikipathways.org)
  • Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nep. (cdc.gov)
  • Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent mineralocorticoid excess where cortisol acts as a mineralocorticoid. (cdc.gov)
  • Weak associations are reported between the HSD11B2 gene, type 1 diabetes mellitus and nephropathy. (cdc.gov)
  • Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and 11-beta-hydroxysteroid dehydrogenase (NADP+) activity . (genecards.org)
  • The human gene for 11 beta-hydroxysteroid dehydrogenase. (wikipedia.org)
  • Although the antiinflammatory activity of GCs is well described, there is also accumulating evidence that GCs are not only inhibitory, but may also enhance immune cell activation and induce gene transcription ( 10 , 11 ). (rupress.org)
  • A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia. (wikipathways.org)
  • Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. (wikipathways.org)
  • The mechanism of the variable and distinct 11β-hydroxysteroid dehydrogenase type 2 gene ( HSD11B2 ) expression in the cortical collecting duct is poorly understood. (ahajournals.org)
  • To clarify the depot-specific impact of 11beta-HSD1, we assessed whether preadipocytes in ASV from mesenteric (as a representative of visceral adipose tissue) and sc tissue displayed 11beta-HSD1 activity in mice. (nih.gov)
  • In vivo, high-fat diet-induced obesity was accompanied by increased visceral fat preadipocyte differentiation in wild-type but not 11beta-HSD1(-/-) mice. (nih.gov)
  • Pancreatic islets isolated from ob/ob mice display type 1 11beta-hydroxysteroid dehydrogenase activity, i.e. in intact cells the reductive reaction prevails, leading from dehydrocorticosterone to corticosterone. (ox.ac.uk)
  • Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob/ob mice and also from human tissue. (ox.ac.uk)
  • To define the direct impact of elevated pancreatic β-cell 11β-HSD1 on insulin secretion, we generated β-cell-specific, 11β-HSD1-overexpressing (MIP-HSD1) mice on a strain background prone to β-cell failure. (diabetesjournals.org)
  • 11β-HSD1 −/− mice showed mild β-cell impairment that was offset by improved glucose tolerance. (diabetesjournals.org)
  • The benefit of higher β-cell 11β-HSD1 exhibited a threshold because homozygous MIP-HSD1 tg/tg mice and diabetic Lep db/db mice with markedly elevated β-cell 11β-HSD1 levels had impaired basal β-cell function. (diabetesjournals.org)
  • This premise is strongly supported by the phenotype of transgenic mice overexpressing 11β-HSD1 in fat or liver, which recapitulates diabetes and insulin-resistant metabolic disease, and by the protection from metabolic disease exhibited by 11β-HSD1 −/− mice ( 3 ). (diabetesjournals.org)
  • To test the hypothesis that increased β-cell 11β-HSD1 is diabetogenic, we used the insulin-I promoter ( 10 ) to drive β-cell-specific 11β-HSD1 elevation in vivo in C57Bl/KsJ mice, a strain prone to high-fat (HF) diet-induced β-cell failure ( 11 ). (diabetesjournals.org)
  • Similarly, mice overexpressing 11β-HSD1 in the liver develop adverse metabolic features but do not become obese ( 5 ). (diabetesjournals.org)
  • 11β-HSD1 KO mice with circulating GC excess are protected from the glucose intolerance, hyperinsulinemia, hepatic steatosis, adiposity, hypertension, myopathy, and dermal atrophy of Cushing syndrome. (pnas.org)
  • Whereas liver-specific 11β-HSD1 KO mice developed a full Cushingoid phenotype, adipose-specific 11β-HSD1 KO mice were protected from hepatic steatosis and circulating fatty acid excess. (pnas.org)
  • Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and hence may explain why aspirin improves glycemic control in type 2 diabetes. (wikipedia.org)
  • The importance of these immunoregulatory cytokines in the maintenance of immune homeostasis in the gut is illustrated by the fact that TGFβ and IL-10-deficient mice develop spontaneous inflammatory bowel disease (for review see reference 1 ). (rupress.org)
  • Importantly, genes belonging to steroid hormone biosynthesis (3 beta-hydroxysteroid dehydrogenase-1, cholesterol side-chain cleavage cytochrome P450, and steroid-11 beta-hydroxylase) were all expressed less in mice on a high-fat diet. (wur.nl)
  • Finally, studies characterizing the skin phenotype of aged 11β-HSD1-null mice reveal exciting morphological similarities to skin from young mice. (bham.ac.uk)
  • In the rare cortisone reductase deficiency, impaired regeneration of active cortisol from inert cortisone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) results in compensatory activation of ACTH secretion and adrenal hyperandrogenism. (cdc.gov)
  • Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1. (wikipathways.org)
  • Hyperandrogenism Due to Cortisone Reductase Deficiency, also known as 11-beta-hydroxysteroid dehydrogenase deficiency type 1 , is related to cortisone reductase deficiency and body mass index quantitative trait locus 11 . (malacards.org)
  • Benzothiazole derivatives as novel inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1. (ox.ac.uk)
  • 11beta-HSD1 deficiency may protect against obesity and its metabolic consequences because of impaired regeneration of cortisol in adipose tissue. (cdc.gov)
  • Corticosterone methyl oxidase type II (CMO II) deficiency: biochemical approach to diagnosis. (wikipathways.org)
  • Steroid 11-beta-hydroxylase deficiency caused by compound heterozygosity for a novel mutation, p.G314R, in one CYP11B1 allele, and a chimeric CYP11B2/CYP11B1 in the other allele. (wikipathways.org)
  • 46,XY disorder of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency. (wikipathways.org)
  • We found that life-long partial deficiency of 11beta-HSD1 prevented memory decline with aging. (qualitycounts.com)
  • Further, the expression of leptin and 11 β-hydroxysteroid dehydrogenase 1 genes were significantly increased in CrR offspring of both the sexes. (pubmedcentralcanada.ca)
  • We demonstrate 11β-HSD1-specific regulation of novel GC target genes that may be dysregulated during ageing which correlate with enzyme activity. (bham.ac.uk)
  • Instead, the expression of 11 beta-hydroxysteroid dehydrogenase type 1 in the Zona glomerulosa of the guinea pig adrenal gland suggests a role of this enzyme in mineralocorticoid synthesis in this hypercortisolic species. (ox.ac.uk)
  • Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with polycystic ovary syndrome. (cdc.gov)
  • Genetic variation in 11beta-HSD1 contributes to enhanced cortisol clearance and compensatory adrenal hyperandrogenism in lean patients with PCOS but may be protective against obesity and some features of the metabolic syndrome. (cdc.gov)
  • Substantial extra-adrenal regeneration of cortisol by 11β-HSD1 has been detected in the splanchnic circulation ( 13 , 14 ), arising mainly from liver ( 15 , 16 ), and in subcutaneous adipose tissue ( 15 ). (diabetesjournals.org)
  • A particular type of hypercortisolism presenting during the above conditions, named functional hypercortisolism, is caused by chronic activation of hypothalamic-pituitary-adrenal (HPA) axis. (medscape.com)
  • Although some studies have illustrated that type 2 diabetics do not have higher levels of ACTH or hypothalamic-pituitary-adrenal (HPA) axis activity than normal individuals, other studies have alternatively illustrated that cortisol levels are increased in diabetics (Chiodini, 2007). (kon.org)
  • Role of local 11 beta-hydroxysteroid dehydrogenase type 2 expression in determining the phenotype of adrenal adenomas. (curehunter.com)
  • Role of local 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) expression in determining the phenotype of adrenal adenomas. (curehunter.com)
  • 11beta-HSD1 mRNA and protein levels were comparable between ASV and adipocyte fractions in both depots. (nih.gov)
  • RESULTS: Dexamethasone decreased insulin-stimulated glucose uptake, decreased IRS1 mRNA and protein expression, and increased inactivating pSer(307) insulin receptor substrate (IRS)-1. (ox.ac.uk)
  • In euglycemic obesity, numerous studies ( 17 - 19 ) have shown that 11β-HSD1 mRNA and activity in subcutaneous adipose tissue is increased, which has been corroborated in vivo using microdialysis ( 20 ). (diabetesjournals.org)
  • Alternative splicing of the primary transcript gives rise to the 2 mRNA and protein isoforms, hGR-alpha and hGR-beta. (medscape.com)
  • Weight loss increases 11beta-hydroxysteroid dehydrogenase type 1 expression in human adipose tissue. (ox.ac.uk)
  • CONCLUSIONS: Increased adipose 11beta-HSD1 expression in women may contribute to glucose intolerance. (ox.ac.uk)
  • We investigated the effect of curcumin, a naturally occurring polyphenol known for its anti-inflammatory properties and inhibitory action on 11β-HSD1 activity, on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). (nih.gov)
  • In obesity, 11β-HSD1 is increased in adipose tissue but decreased in liver. (diabetesjournals.org)
  • Cortisol is an important regulator of energy homeostasis, particularly in the liver and adipose tissue ( 1 ). (diabetesjournals.org)
  • Obese rodents exhibit tissue-specific dysregulation of 11β-HSD1, usually with upregulation in adipose tissue and downregulation in liver ( 6 , 7 ). (diabetesjournals.org)
  • 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. (wikipedia.org)
  • INCB13739 completely inhibits the production of intra-adipose and intra-hepatic cortisol by 11beta-HSD1, while maintaining normal systemic cortisol levels, which are essential for immune function and response to stress. (drugbank.ca)
  • Increased rates of co-morbidities such as type 2 diabetes and hepatic damage in overweight adolescents indicate that the young are not protected from the metabolic perturbations that accompany excess adipose tissue stores. (nih.gov)
  • 11Beta-hydroxysteroid dehydrogenase type 1 in human disease: a novel therapeutic target. (nih.gov)
  • 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. (ox.ac.uk)
  • Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism. (ox.ac.uk)
  • We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. (ox.ac.uk)
  • Thus, human, rat, and mouse 11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid dehydrogenase from hamster liver, but differ fundamentally from the latter in that 7beta-OH rather than 7alpha-OH dehydrogenase constitutes the second activity. (ox.ac.uk)
  • Using monodispersity as a screening criterion, we have also optimized the purification process by evaluating various solubilizing systems for the chromatographic steps, finally obtaining stable monodisperse preparations of both human and guinea pig 11beta-HSD1. (ox.ac.uk)
  • Moreover, active site titration of human 11beta-HSD1 revealed that at least 75% of the protein in a typical preparation represents active enzyme. (ox.ac.uk)
  • Here, we report the discovery and synthesis of a series of novel benzothiazole derivatives and their inhibitory activities against 11beta-HSD1 from human hepatic microsomes measured using a radioimmunoassay (RIA) method. (ox.ac.uk)
  • Docking studies with the benzothiazole derivative 1 into the crystal structure of human 11beta-HSD1 revealed how the molecule may interact with the enzyme and cofactor. (ox.ac.uk)
  • Importantly, these purified soluble enzymes also display a hyperbolic dependence of reaction velocity versus substrate concentration in 11-oxoreduction with K(m) values of 0.8 microm (human) and 0.6 microm (guinea pig), close to the values obtained from intact cells. (ox.ac.uk)
  • The most robust evidence in support of a pathogenetic role of this enzyme in the development of the metabolic syndrome has been reported in experimental animals, whereas results of human studies are less convincing with several case control and cross-sectional studies showing an association between with 11beta-HSD-1 setpoint and individual features of the metabolic syndrome. (unimi.it)
  • The human GR is a modular protein composed of distinct regions illustrated in panel B in the image below, as follows: (1) The amino-terminal A/B region, also called immunogenic or N-terminal domain (NTD) and (2) the C, D, and E regions, which correspond to the DNA-binding domain, the hinge region, and the ligand-binding domain, respectively. (medscape.com)
  • Bord S, Horner A, Beavan S, Compston J. Estrogen receptors alpha and beta are differentially expressed in developing human bone. (labome.org)
  • Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II. (wikipathways.org)
  • The translational efficacy of a nonsteroidal progesterone receptor antagonist, 4-[3-cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy,-2,6-dimethylbenzonitrile (PF-02413873), on endometrial growth in macaque and human. (discoverx.com)
  • 17β-Oestradiol promotes differentiation of human embryonic stem cells into dopamine neurons via cross-talk between insulin-like growth factors-1 and oestrogen receptor β. (bl.uk)
  • Resveratrol shows metabolic benefits for obese: Study - Nutra USA, 10/11/10 - 'When human fat cells were exposed to IL-1B, the researchers noted increases in the secretion of pro-inflammatory compounds , including IL6, IL8, MCP-1. (qualitycounts.com)
  • Inflammatory mediators down-regulate 11beta-hydroxysteroid dehydrogenase type 2 in a human lung epithelial cell line BEAS-2B and the rat lung. (curehunter.com)
  • Enzyme activity has been quantified using a stable isotope tracer, 9,11,12,12-[ 2 H] 4 cortisol (d4-cortisol), from which the 11-deuterium is removed during interconversion with cortisone, allowing quantification of dilution of d4-cortisol by d3-cortisol and hence of 11β-HSD1 activity, independently from the influence of other cortisol-metabolizing enzymes ( 12 ). (diabetesjournals.org)
  • SUNAK, N., GREEN, D. F., ABEYDEERA, L. R., THURSTON, L. M. & MICHAEL, A. E. (2007) Implication of cortisol and 11beta-hydroxysteroid dehydrogenase enzymes in the development of porcine (Sus scrofa domestica) ovarian follicles and cysts. (rvc.ac.uk)
  • Oxidative Medicine and Cellular Longevity , Vol. 2016, p. 1. (cambridge.org)
  • The increased frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and may, in part, explain the enhanced salt sensitivity observed in patients with type 1 diabetes. (cdc.gov)
  • Cortisol Metabolism and Hepatic Expression of 11 beta-Hydroxysteroid Dehydrogenase Type 1 in Patients with Non Alcoholic Fatty Liver Disease. (ox.ac.uk)
  • Samples were obtained from the hepatic vein and an arterialized hand vein at steady state and after oral administration of cortisone (5 mg) to estimate whole-body and liver 11β-HSD1 activity using tracer dilution. (diabetesjournals.org)
  • CONCLUSIONS Whole-body 11β-HSD1 activity is increased in obese men with type 2 diabetes, whereas liver 11β-HSD1 activity is sustained, unlike in euglycemic obesity. (diabetesjournals.org)
  • Conversely, hepatic 11β-HSD1 activity, assessed by measuring plasma cortisol after oral administration of cortisone, is reduced in obesity ( 17 , 19 , 21 ), although it is uncertain whether increased inactivation of cortisone and cortisol by A-ring reductases in the liver ( 22 ) contributes to the difference in plasma cortisol. (diabetesjournals.org)
  • 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a microsomal enzyme abundantly expressed in brain, liver, and fat tissue [ 1 ]. (mdpi.com)
  • Specific Aim 1: To perform a cross-sectional study of women with PCOS and normal controls matched for age and body mass index, and measure insulin sensitivity and visceral fat, as well as (a) 24-hour CPR, ACTH, free cortisol, and cortisol binding globulin (CBG), (b) adipocyte, liver, and whole body HSD 1 activity, and (c) androgen levels. (clinicaltrials.gov)
  • The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. (hindawi.com)
  • The epidemic increase in obesity has been paralleled by the rise in cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, asthma, neurodegenerative diseases, and certain types of cancer [ 1 , 2 ] and subsequently linked to reduced life expectancy and premature death [ 3 ]. (hindawi.com)
  • The main action of GH is to cause the liver to produce a hormone called IGF-1. (healthengine.com.au)
  • Here, we analyzed for the first time whether the 11β-HSD2 expression is modulated by microRNAs (miRNAs). (ahajournals.org)
  • THURSTON, L. M., ABAYASEKARA, D. R. & MICHAEL, A. E. (2007) 11beta-Hydroxysteroid dehydrogenase expression and activities in bovine granulosa cells and corpora lutea implicate corticosteroids in bovine ovarian physiology. (rvc.ac.uk)
  • 11β-HSD1 activity was increased in skin from older vs. younger donors with increased expression in dermal fibroblasts from the former. (bham.ac.uk)
  • Increased expression of 11 beta-hydroxysteroid dehydrogenase type 2 in the lungs of patients with acute respiratory distress syndrome. (curehunter.com)
  • A novel role of 11beta-HSD1 in 7-oxosterol metabolism was discovered and investigated using recombinant 11beta-HSD1 orthologs. (ki.se)
  • 1 Molecular Metabolism Group, University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, U.K. (diabetesjournals.org)
  • [ 19 , 20 ] In obesity, postulated mechanisms of hyperactivation of HPA axis include hyper-responsiveness to different neuropeptides, stress events, dietary factors, as well as a stimulation caused by augmented peripheral metabolism and clearance of cortisol by reduced conversion of cortisone to cortisol by 11β-HSD1 and increased conversion of cortisol to 5α-reduced derivatives. (medscape.com)
  • Conclusions We identify an entirely novel component of therapeutic GC action, whereby following their systemic metabolism, they require peripheral reactivation and amplification by 11β-HSD1 at sites of inflammation to deliver their anti-inflammatory therapeutic effects. (bmj.com)
  • This suggests a novel depot-specific control over 11beta-HSD1 enzyme activity. (nih.gov)
  • 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. (nih.gov)
  • The results show that the hydrophobic enzyme 11beta-HSD1 can be expressed with high activity as a full length, membrane bound enzyme in the yeast system Pichia pastoris and can be purified as a soluble, N-terminally truncated form expressed in E.coli, by using metal-chelate chromatography. (ki.se)
  • Importantly, 11beta-HSD1 activity appears to be intrinsically linked to all features of the metabolic syndrome, which could at least in animal experiments be modulated by use of synthetic selective inhibitors. (ox.ac.uk)
  • Biochemical analysis showed that the 3-hydroxyacyl-CoA dehydrogenase activity of the D-bifunctional protein was completely inactive, whereas the enoyl-CoA hydratase component was active. (steroids-australia.net)
  • G in the third intron rs12086634, which associates with lower 11beta-HSD1 activity) in PCOS with and without obesity. (cdc.gov)
  • To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects. (diabetesjournals.org)
  • this evidence of increased mineralocorticoid activity was associated with increased aldosterone metabolites and decreased 11β-hydroxysteroid dehydrogenase type 2 activity. (whiterose.ac.uk)
  • To gain insight into potentially relevant miRNAs in vivo, we investigated 2 models with differential 11β-HSD2 activity linked with salt-sensitive hypertension. (ahajournals.org)
  • THURSTON, L. M., JONAS, K. C., ABAYASEKARA, D. R. & MICHAEL, A. E. (2003) Ovarian modulators of 11beta-hydroxysteroid dehydrogenase (11beta HSD) activity in follicular fluid from bovine and porcine large antral follicles and spontaneous ovarian cysts. (rvc.ac.uk)
  • 11beta-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets. (lenus.ie)
  • Elevated 11β-HSD1 is also found in pancreatic islets of obese/diabetic rodents and is hypothesized to suppress insulin secretion and promote diabetes. (diabetesjournals.org)
  • Lipid derivatives activate GPR119 and trigger GLP-1 secretion in primary murine L-cells. (nih.gov)
  • Type 2 Diabetes develops through abnormal insulin action and insulin secretion (Goldstein, 2002). (kon.org)
  • Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. (discoverx.com)
  • However, although circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) has been postulated as a pathogenic mechanism. (ox.ac.uk)
  • Selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) have considerable potential as treatments for metabolic diseases, such as diabetes mellitus type 2 or obesity. (ox.ac.uk)
  • Type 2 diabetes prevalence has risen dramatically in parallel with the worldwide increase in obesity ( 1 ). (diabetesjournals.org)
  • Exposure of such a thrifty phenotype to excessive nutrition postnatally overloads its reduced metabolic capacity, which could manifest in metabolic disorders such as obesity, cardiovascular disease, and type 2 diabetes in later life ( 2 ). (pubmedcentralcanada.ca)
  • This paper is a review of the role of cortisol and abdominal obesity in the epidemic of type 2 Diabetes. (kon.org)
  • Future efforts in this related struggle against both obesity and type 2 diabetes should encompass a strong focus on cortisol so such prevention and treatment can successfully advance. (kon.org)
  • 2 Obesity affects almost all organ systems and because of the adverse effects of excess fat deposition is a risk factor for type 2 diabetes mellitus, cardiovascular and renal disease. (ahajournals.org)
  • 9 Sex also plays an important role in the development of obesity-mediated nephropathies 10 with females having a reduced risk of developing renal disease, 11 whereas males exhibit a faster progression. (ahajournals.org)
  • The specific relationships between obesity and cardiovascular risk vary considerably with gender, race, and type of heart disease. (nih.gov)
  • RESEARCH DESIGN AND METHODS Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[ 2 H] 4 cortisol (40%) and cortisol (60%) at 1.74 mg/h. (diabetesjournals.org)
  • This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects. (diabetesjournals.org)
  • According to the US National Commission on Diabetes, the likelihood of acquiring type 2 diabetes is 2-fold for mildly obese individuals, 5-fold for moderately obese individuals, and 10-fold for the severely obese individuals (Pi-Sunyer, 2007). (kon.org)
  • 1 The 2008 World Health Organization statistics indicated that ≈1.5 billion adults are overweight, of which 200 million men and 300 million women were classed as obese, a figure predicted to rise by 50% by 2015. (ahajournals.org)
  • Whereas the type 1 enzyme (11beta-HSD1) is in vitro a NADP(H)- dependent bidirectional enzyme, it reduces in most instances in vivo cortisone to active cortisol. (ox.ac.uk)
  • Type 1 11 beta-hydroxysteroid dehydrogenase constitutes a prereceptor control mechanism through its ability to reduce dehydroglucocorticoids to the receptor ligands cortisol and corticosterone in vivo. (ox.ac.uk)
  • Although this strengthens the growing contention that 11β-HSD1 inhibitors are an effective therapeutic treatment for metabolic syndrome through actions in multiple organ systems ( 9 ), any physiological role of β-cell 11β-HSD1, and indeed the potentially pathogenic role ( 5 - 8 ) of elevated 11β-HSD1 in islets in vivo, remains uncertain. (diabetesjournals.org)
  • Selective 11β-HSD1 inhibitors are efficacious in several rodent models of diabetes ( 8 - 11 ). (diabetesjournals.org)
  • In our efforts to prepare potent and selective 11β-HSD1 inhibitors based on a pharmacophore structure designed in silico by the Lagos group, we set out to synthesize several 3,5-disubstituted 1,2,4-oxadiazole derivatives. (mdpi.com)
  • These findings have immediate significance for current therapeutic strategies for type 2 diabetes. (diabetesjournals.org)
  • We investigated the contribution of 11β-HSD1 to the anti-inflammatory properties of the active GC corticosterone, administered at therapeutic doses in murine models of polyarthritis. (bmj.com)
  • Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). (lenus.ie)
  • 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an intraluminally oriented, endoplasmic reticulum (ER)-bound enzyme catalyzing the interconversion between inactive cortisone and hormonally active cortisol. (ox.ac.uk)
  • Biochemical studies indicated a decreased rate of conversion of active cortisol to cortisone, and the authors postulated a defect in 11-beta-hydroxy oxidation of cortisol. (steroids-australia.net)
  • Elevenbeta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), a key intracellular enzyme which catalyses the conversion of inactive cortisone to active cortisol, has been implicated in the development of the metabolic syndrome. (unimi.it)
  • The possible roles of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in cardiac fibrosis in the spontaneously hypertensive rat. (curehunter.com)
  • 11beta-HSD1 was highly expressed in freshly isolated ASV cells, predominantly in preadipocytes. (nih.gov)
  • In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity). (genecards.org)
  • Estrogens play a role in almost all cells and tissues in the body (Figure 1 ). (frontiersin.org)
  • Although efficient intestinal immune responses protect the host from invading pathogens, the inappropriate activation of intestinal T cells may also result in chronic inflammatory reactions and tissue destruction, e.g., as observed in inflammatory bowel disease (for review see reference 1 ). (rupress.org)
  • On the other, a specific type of sensory neuron (scolopidial neurons) shows defects in microtubule organization and detaches from its support cells. (labome.org)
  • GCs act on almost all types of immune cells and were long recognized to perform salient immunosuppressive and anti-inflammatory functions through various genomic and non-genomic mechanisms. (frontiersin.org)
  • Characterization of isoprenaline- and salmeterol-stimulated interactions between beta2-adrenoceptors and beta-arrestin 2 using beta-galactosidase complementation in C2C12 cells. (discoverx.com)
  • In addition, it is well established that the performance of immune cells is largely influenced by metabolic cues and both metabolic and immune systems are highly interdependent [ 1 ]. (hindawi.com)
  • The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type 2 performs the reverse reaction. (ox.ac.uk)
  • Investigated for use/treatment in diabetes mellitus type 2 and diabetes prevention. (drugbank.ca)
  • although the morbidity and mortality rates for countless diseases have been reduced due to advances in medical research and high standard of living, the rate of type 2 diabetes mellitus increases. (kon.org)