Hydroxysteroid Dehydrogenases: Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-.11-beta-Hydroxysteroid Dehydrogenase Type 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.11-beta-Hydroxysteroid Dehydrogenase Type 2: 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.17-Hydroxysteroid Dehydrogenases: A class of enzymes that catalyzes the oxidation of 17-hydroxysteroids to 17-ketosteroids. EC 1.1.-.3-Hydroxysteroid Dehydrogenases: Catalyze the oxidation of 3-hydroxysteroids to 3-ketosteroids.11-beta-Hydroxysteroid Dehydrogenases: 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.20-Hydroxysteroid Dehydrogenases: 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).Steroid 17-alpha-Hydroxylase: 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.3-alpha-Hydroxysteroid Dehydrogenase (B-Specific): 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.Hydrocortisone: 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.Estradiol Dehydrogenases: 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 1.1.1.62Cortisone: 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)Sulfotransferases: 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.Alcohol Oxidoreductases: 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).Steroids: 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)NAD: 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)Carbohydrate Dehydrogenases: 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.Kinetics: The rate dynamics in chemical or physical systems.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Testosterone: 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.L-Lactate Dehydrogenase: 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.Androsterone: A metabolite of TESTOSTERONE or ANDROSTENEDIONE with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.Alcohol Dehydrogenase: 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.TetrahydrocortisolAntineoplastic Protocols: Clinical protocols used to inhibit the growth or spread of NEOPLASMS.TetrahydrocortisoneGlyceraldehyde-3-Phosphate Dehydrogenases: 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.Carbenoxolone: 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.Receptors, Mineralocorticoid: 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.20-alpha-Hydroxysteroid Dehydrogenase: An enzymes that catalyzes the reversible reduction-oxidation reaction of 20-alpha-hydroxysteroids, such as from PROGESTERONE to 20-ALPHA-DIHYDROPROGESTERONE.IMP Dehydrogenase: An enzyme that catalyzes the dehydrogenation of inosine 5'-phosphate to xanthosine 5'-phosphate in the presence of NAD. EC 1.1.1.205.Drug Design: 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.Glucocorticoids: 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.Mineralocorticoid Excess Syndrome, Apparent: 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.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.Metabolic Syndrome X: 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)PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Serial Publications: Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the ENDOCRINE SYSTEM.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Glucose Clamp Technique: Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Nucleoside Q: A modified nucleoside which is present in the first position of the anticodon of tRNA-tyrosine, tRNA-histidine, tRNA-asparagine and tRNA-aspartic acid of many organisms. It is believed to play a role in the regulatory function of tRNA. Nucleoside Q can be further modified to nucleoside Q*, which has a mannose or galactose moiety linked to position 4 of its cyclopentenediol moiety.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Androstanes: The family of steroids from which the androgens are derived.Oxidoreductases, O-Demethylating: Drug metabolizing enzymes which oxidize methyl ethers. Usually found in liver microsomes.Lawyers: Persons whose profession is to give legal advice and assistance to clients and represent them in legal matters. (American Heritage Dictionary, 3d ed)

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)

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 ...
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.
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
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
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
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 ...
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 ...
[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 ...
Looking for the definition of 11-beta-hydroxysteroid dehydrogenases? Find out what is the full meaning of 11-beta-hydroxysteroid dehydrogenases on Abbreviations.com! Beta is one option -- get in to view more @ The Webs largest and most authoritative acronyms and abbreviations resource.
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 ...
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.. ...
Looking for online definition of 3-beta (beta)-hydroxysteroid sulfatase in the Medical Dictionary? 3-beta (beta)-hydroxysteroid sulfatase explanation free. What is 3-beta (beta)-hydroxysteroid sulfatase? Meaning of 3-beta (beta)-hydroxysteroid sulfatase medical term. What does 3-beta (beta)-hydroxysteroid sulfatase mean?
The enzyme 3beta/17beta-hydroxysteroid dehydrogenase (3beta/17beta-HSD) is a steroid-inducible component of the Gram-negative bacterium Conramonas testosteroni. It catalyzes the reversible reduction/ dehydrogenation of the oxo/beta-hydroxy groups at positions 3 and 17 of steroid compounds, including hormones and isobile acids. Crystallographic analysis at 1.2 Angstrom resolution reveals the enzyme to have nearly identical subunits that form a tetramer with 222 symmetry. This is one of the largest oligomeric structures refined at this resolution. The subunit consists of a monomer with a single-domain structure built around a seven-stranded beta-sheet flanked by six alpha-helices. The active site contains a Ser-Tyr-Lys triad, typical for short-chain dehydrogenases/reductases (SDR). Despite their highly diverse substrate specificities, SDR members show a close to identical folding pattern architectures and a common catalytic mechanism. In contrast to other SDR apostructures determined, the ...
We have investigated the effects of fetal growth restriction, induced by restriction of placental growth and function (PR), on 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD-1) and 11betaHSD-2 messenger RNA (mRNA) expression in fetal tissues in the sheep, using Northern blot analysis. Fetal liver, kidney, and adrenals were collected from normally grown fetuses at 90 days (n = 6), 125 days (n = 6), and 141-145 days (n = 7) and from PR fetuses at 141-145 days (n = 6). Expression of 11betaHSD-1 mRNA in the fetal liver increased significantly between 125 days (7.4+/-0.8) and 141-145 days gestation (27+/-5.3). There was also an approximately 2-fold increase in the ratio of 11betaHSD-1 mRNA/18S rRNA expression in the PR group (53.8+/-7.9) compared with that in control animals at 141-145 days gestation. There was a significant decrease in 11betaHSD-2 mRNA in fetal adrenals between 125 days (41.6+/-2.4) and 141-145 days (26.7+/-1.1) gestation, but there was no effect of PR on the expression of ...
TY - JOUR. T1 - 11-ketotestosterone is a major androgen produced in human gonads. AU - Imamichi, Yoshitaka. AU - Yuhki, Koh Ichi. AU - Orisaka, Makoto. AU - Kitano, Takeshi. AU - Mukai, Kuniaki. AU - Ushikubi, Fumitaka. AU - Taniguchi, Takanobu. AU - Umezawa, Akihiro. AU - Miyamoto, Kaoru. AU - Yazawa, Takashi. PY - 2016/10/1. Y1 - 2016/10/1. N2 - Context: 11-ketotestosterone (11-KT) is a novel class of active androgen. However, the detail of its synthesis remains unknown for humans. Objective: The objective of this study was to clarify the production and properties of 11-KT in human. Design, Participants, and Methods: Expression of cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 (key enzymes involved in the synthesis of 11-KT) were investigated in human gonads. The production of 11-KT was investigated in Leydig cells. Plasma concentrations of testosterone and 11-KT were measured in 10 women and 10 men of reproductive age. Investigation of its properties was performed using ...
Hardy, Rowan S., Doig, Craig L., Hussain, Zahrah, OLeary, Mary, Morgan, Stuart A., Pearson, Mark J., Naylor, Amy, Jones, Simon W., Filer, Andrew, Stewart, Paul M., Buckley, Christopher D., Lavery, Gareth G., Cooper, Mark S. and Raza, Karim (2016). 11β-Hydroxysteroid dehydrogenase type 1 within muscle protects against the adverse effects of local inflammation. Journal of Pathology, 240 (4), pp. 472-483. Pearson, Mark J. and Jones, Simon W. (2016). Review:Long Noncoding RNAs in the Regulation of Inflammatory Pathways in Rheumatoid Arthritis and Osteoarthritis. Arthritis and Rheumatology, 68 (11), pp. 2575-2583. Pearson, Mark J., Philp, Ashleigh M., Heward, James A., Roux, Benoit T., Walsh, David A., Davis, Edward T., Lindsay, Mark A. and Jones, Simon W. (2016). Long Intergenic Noncoding RNAs Mediate the Human Chondrocyte Inflammatory Response and Are Differentially Expressed in Osteoarthritis Cartilage. Arthritis and Rheumatology, 68 (4), pp. 845-856. ...
Background Impaired corticosteroid action caused by genetic and environmental influence, including exposure to hazardous xenobiotics, contributes to the development and progression of metabolic diseases, cardiovascular complications and immune disorders. Novel strategies are thus needed for identifying xenobiotics that interfere with corticosteroid homeostasis. 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) and mineralocorticoid receptors (MR) are major regulators of corticosteroid action. 11β-HSD2 converts the active glucocorticoid cortisol to the inactive cortisone and protects MR from activation by glucocorticoids. 11β-HSD2 has also an essential role in the placenta to protect the fetus from high maternal cortisol concentrations. Methods and Principal Findings We employed a previously constructed 3D-structural library of chemicals with proven and suspected endocrine disrupting effects for virtual screening using a chemical feature-based 11β-HSD pharmacophore. We tested several in silico
An intact genome is essential for kidney growth and differentiation, but less is known about whether, and how, an altered fetal milieu modifies these processes. Maternal low-protein diets perturb growth of the metanephros, the precursor of the mature kidney. Fetal corticosteroid overexposure may, in part, mediate this, because such diets downregulate placental 11beta-hydroxysteroid dehydrogenase-2, which degrades maternal corticosteroids. We report that glucocorticoid and mineralocorticoid receptors are expressed in mouse metanephric epithelia. Metanephroi maintained in organ culture with hydrocortisone (1.4 or 14 microM) underwent a dose-dependant deceleration of overall growth accompanied by cyst formation. Dexamethasone, a glucocorticoid, reproduced these outcomes, but aldosterone, a mineralocorticoid, did not. Hydrocortisone upregulated transcripts levels of cadherin-11 and downregulated prospero-related homeobox-1, hence mimicking reported effects of maternal low-protein diet. Hydrocortisone also
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2 Answers - Posted in: pain, cortisone, surgery, doctor, knee, tumor - Answer: Im not sure if its normal. My doctor warned me that the cortisone ...
Scientists now say that a cancers specific genetic or biological profile may have more in common with a cancer that started in another
A nurse who was a calming presence in the operating room for 58 years has finally retired, leaving behind an impact that colleagues say is
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Looking for information on 3 beta hydroxysteroid dehydrogenase deficiency? Medigest has all you need to know about 3 beta hydroxysteroid dehydrogenase deficiency - Symptoms and Signs, Causes, Treatments and definition
TY - JOUR. T1 - Role of glucocorticoid receptor and CCAAT/enhancer-binding protein α in the feed-forward induction of 11β-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts. AU - Yang, Zhen. AU - Guo, Chunming. AU - Zhu, Ping. AU - Li, Wenjiao. AU - Myatt, Leslie. AU - Sun, Kang. PY - 2007/11/1. Y1 - 2007/11/1. N2 - The amount of cortisol available to its receptors is increased by the pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which converts cortisone to cortisol. We examined the molecular mechanisms of the feedback effect of cortisol on 11β-HSD1 mRNA expression in human amnion fibroblasts. Our data showed that cortisol-induced 11β-HSD1 mRNA expression dose dependently in amnion fibroblasts, which could be completely blocked both by the mRNA transcription inhibitor 5,6-dichlorobenzimidazole riboside and by the glucocorticoid receptor (GR) antagonist RU486, and partially blocked by global inhibition of CCAAT/enhancer-binding ...
... s bind to the mineralocorticoid receptor in the cell cytosol, and are able to freely cross the lipid bilayer of the cell. This type of receptor becomes activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex translocates into the cell nucleus, where it binds to many hormone response elements (HREs) in the promoter region of the target genes in the DNA. The opposite mechanism is called transrepression. The hormone receptor without ligand binding interacts with heat shock proteins and prevents the transcription of targeted genes. Aldosterone and cortisol (a glucosteroid) have similar affinity for the mineralocorticoid receptor; however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids. This enzyme, 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2), catalyzes the ...
"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 ... "Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans". Diabetes. 58 (1): 46-53. doi: ...
... 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 ...
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 ... The systematic name of this enzyme class is 11beta-hydroxysteroid:NADP+ 11-oxidoreductase. Other names in common use include ... the two substrates of this enzyme are 11beta-hydroxysteroid and NADP+, whereas its 3 products are 11-oxosteroid, NADPH, and H+ ...
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 ...
... 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 ... 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 ...
3(or 17)beta-hydroxysteroid dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular and ... 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 ...
... 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 ...
... 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 ...
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, ...
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 ...
Licorice inhibits the 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2) enzyme resulting in inappropriate ...
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 ...
Rheault P, Dufort I, Soucy P, Luu-The V (1999). "Assignment of HSD17B5 encoding type 5 17 beta-hydroxysteroid dehydrogenase to ... 11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a ... 3-alpha hydroxysteroid dehydrogenase, type II)". Tian Y, Zhao L, Zhang H, Liu X, Zhao L, Zhao X, Li Y, Li J (2014). "AKR1C3 ... also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is ...
"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. ... DHRS7B is a member of the short chain dehydrogenase/reductase (SDR) superfamily and possesses characteristic features of an SDR ... Dehydrogenase/reductase (SDR family) member 7B". "Genecards: DHRS7B Gene protein-coding GIFtS 47". Tannin GM, Agarwal AK, ...
These hormones and medications include insulin, epinephrine, and other beta agonists (e.g. salbutamol or salmeterol), and ... Type B intercalated cells in the collecting duct reabsorb H+ and secrete HCO3. Protons are reabsorbed via both H+-K+ATPases and ... this facilitated diffusion occurs in both Type B intercalated cells and Principal cells in the collecting duct). 2) Metabolic ... Hypertension and hypokalemia can also be seen with a deficiency of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which ...
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, ...
"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, ... hydroxysteroid dehydrogenase AKR1C1 Shikita M, Inano H, Tamaoki B (1967). "Further studies on 20-alpha-hydroxysteroid ...
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 ...
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[ ...
... 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) ...
... ... 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
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 ...
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 ...
Reduced adipose 11beta-HSD1 expression and increased plasma cortisol during longer therapy with rosiglitazone probably reflect ... In 12 healthy men, 4-5 wk of rosiglitazone increased insulin sensitivity during insulin infusion but did not change 11beta-HSD1 ... OBJECTIVE: Our objective was to test whether PPAR agonists alter cortisol secretion and peripheral regeneration by 11beta-HSD1 ... In 12 men with type 2 diabetes 12 wk of rosiglitazone reduced arteriovenous cortisone extraction across abdominal sc adipose ...
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 ...
... 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 ...
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 ...
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 ...
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 ...
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 ... The systematic name of this enzyme class is 11beta-hydroxysteroid:NADP+ 11-oxidoreductase. Other names in common use include ... the two substrates of this enzyme are 11beta-hydroxysteroid and NADP+, whereas its 3 products are 11-oxosteroid, NADPH, and H+ ...
Rat 11-Beta-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) ELISA Kit Abbexa Ltd ...
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 ...
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 ...
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 ...
Publication types * Research Support, Non-U.S. Govt MeSH terms * 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism ... Trevor Teich 1 , Jacklyn A Pivovarov 1 , Deanna P Porras 1 , Emily C Dunford 1 , Michael C Riddell 1 ... 1 Muscle Health Research Centre, School of Kinesiology and Health Science, York University , Toronto, Ontario , Canada. ... and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk. The wheel locked ...
11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. ... Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) ... 11.. The use of spherical reconstituted high density lipoprotein for the measurement of cholesteryl ester transfer protein ... Lipid derivatives activate GPR119 and trigger GLP-1 secretion in primary murine L-cells. ...
  • 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)
  • 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)
  • 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)
  • 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)
  • For example, transgenic mice selectively overexpressing 11β-HSD1 in adipose tissue develop obesity, insulin resistance, hypertension, and dyslipidemia ( 3 , 4 ). (diabetesjournals.org)
  • Similarly, mice overexpressing 11β-HSD1 in the liver develop adverse metabolic features but do not become obese ( 5 ). (diabetesjournals.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)
  • Indeed, simply reducing daily food intake 20-40% below the ad libitum amount, or providing food intermittently, rather than continuously, has been shown to significantly reduce the risk of developing diseases such as cancer, type 2 diabetes, and renal failure and can extend lifespan by up to 40% in rats and mice ( 3 , 6 , 7 ). (pnas.org)
  • Laboratory mice and rats are typically housed either singly or in groups of 2-5 per cage with 1-3 square feet of floor space covered with bedding. (pnas.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)
  • 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)
  • 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)
  • To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects. (diabetesjournals.org)
  • 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)
  • 14. The method of claim 1, wherein EAAT2 protein expression is increased in vivo. (freepatentsonline.com)
  • Kiran SG, Dorisetty RK, Umrani MR, Boindala S, Bhonde RR, Chalsani M, Singh H, Venkatesan V (2011) Pyridoxal 5′ phosphate protects islets against streptozotocin-induced beta-cell dysfunction-in vitro and in vivo. (springer.com)
  • 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)
  • 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)
  • 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)
  • We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. (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)
  • 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)
  • 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)
  • Bord S, Horner A, Beavan S, Compston J. Estrogen receptors alpha and beta are differentially expressed in developing human bone. (labome.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)
  • 2. The method of claim 1, wherein the subject is a human. (freepatentsonline.com)
  • Enasidenib drives human erythroid differentiation independently of isocitrate dehydrogenase 2. (stanford.edu)
  • The most important reaction for this class of steroids is the reversible C11 keto/beta-hydroxyl conversion between receptor-binding 11beta-OH steroids and the nonbinding 11-oxo compounds, carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). (ox.ac.uk)
  • 13. The method as in any one of claims 1 , 5 or 8 , wherein the cannabidiol derivative compound of the pharmaceutical composition is further combined with one or more anti-inflammatory compounds or immunomodulatory drugs. (freepatentsonline.com)
  • The invention concerns 4-aminomethyl-1-aryl-cyclohexylamine compounds, methods for producing same, pharmaceutical formulations containing said compounds and the. (patents.com)
  • This invention comprises the compounds of formula (I): ##STR00001## wherein r, s, t, Y.sup.1 Y.sup.2, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and. (patents.com)
  • Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS. (drugbank.ca)
  • Described herein are methods of treating or preventing neurological disease and disease symptoms using beta-lactam compounds, and compounds useful for treating disease and disease symptoms. (freepatentsonline.com)
  • We have investigated the effects of fetal growth restriction, induced by restriction of placental growth and function (PR), on 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD-1) and 11betaHSD-2 messenger RNA (mRNA) expression in fetal tissues in the sheep, using Northern blot analysis. (edu.au)
  • 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)
  • 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)
  • In 12 men with type 2 diabetes 12 wk of rosiglitazone reduced arteriovenous cortisone extraction across abdominal sc adipose tissue and reduced 11beta-HSD1 mRNA in sc adipose tissue but increased plasma cortisol concentrations. (ox.ac.uk)
  • Alternative splicing of the primary transcript gives rise to the 2 mRNA and protein isoforms, hGR-alpha and hGR-beta. (medscape.com)
  • There was also an approximately 2-fold increase in the ratio of 11betaHSD-1 mRNA/18S rRNA expression in the PR group (53.8+/-7.9) compared with that in control animals at 141-145 days gestation. (edu.au)