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.TetrahydrocortisolAldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. This enzyme was formerly classified as EC 1.1.1.70.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.Placenta: A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Pregnancy Complications: Conditions or pathological processes associated with pregnancy. They can occur during or after pregnancy, and range from minor discomforts to serious diseases that require medical interventions. They include diseases in pregnant females, and pregnancies in females with diseases.Pregnancy Outcome: Results of conception and ensuing pregnancy, including LIVE BIRTH; STILLBIRTH; SPONTANEOUS ABORTION; INDUCED ABORTION. The outcome may follow natural or artificial insemination or any of the various ASSISTED REPRODUCTIVE TECHNIQUES, such as EMBRYO TRANSFER or FERTILIZATION IN VITRO.Multilingualism: The ability to speak, read, or write several languages or many languages with some facility. Bilingualism is the most common form. (From Random House Unabridged Dictionary, 2d ed)Pregnancy, Animal: The process of bearing developing young (EMBRYOS or FETUSES) in utero in non-human mammals, beginning from FERTILIZATION to BIRTH.Smoking: Inhaling and exhaling the smoke of burning TOBACCO.Language: A verbal or nonverbal means of communicating ideas or feelings.Progesterone Reductase: An enzyme that catalyzes the reduction of a 3 beta-hydroxy-delta(5)-steroid to 3-oxo-delta(4)-steroid in the presence of NAD. It converts pregnenolone to progesterone and dehydroepiandrosterone to androstenedione. EC 1.1.1.145.Glycyrrhetinic Acid: An oleanolic acid from GLYCYRRHIZA that has some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation.17-alpha-Hydroxyprogesterone: A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.Hydroxyprogesterones: Metabolites or derivatives of PROGESTERONE with hydroxyl group substitution at various sites.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Glycyrrhizic Acid: A widely used anti-inflammatory agent isolated from the licorice root. It is metabolized to GLYCYRRHETINIC ACID, which inhibits 11-BETA-HYDROXYSTEROID DEHYDROGENASES and other enzymes involved in the metabolism of CORTICOSTEROIDS. Therefore, glycyrrhizic acid, which is the main and sweet component of licorice, has been investigated for its ability to cause hypermineralocorticoidism with sodium retention and potassium loss, edema, increased blood pressure, as well as depression of the renin-angiotensin-aldosterone system.Child Development Disorders, Pervasive: Severe distortions in the development of many basic psychological functions that are not normal for any stage in development. These distortions are manifested in sustained social impairment, speech abnormalities, and peculiar motor movements.Autistic Disorder: A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V)Asperger Syndrome: A disorder beginning in childhood whose essential features are persistent impairment in reciprocal social communication and social interaction, and restricted, repetitive patterns of behavior, interests, or activities. These symptoms may limit or impair everyday functioning. (From DSM-5)Serotonin Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Fetal Alcohol Spectrum Disorders: An umbrella term used to describe a pattern of disabilities and abnormalities that result from fetal exposure to ETHANOL during pregnancy. It encompasses a phenotypic range that can vary greatly between individuals, but reliably includes one or more of the following: characteristic facial dysmorphism, FETAL GROWTH RETARDATION, central nervous system abnormalities, cognitive and/or behavioral dysfunction, BIRTH DEFECTS. The level of maternal alcohol consumption does not necessarily correlate directly with disease severity.Social Behavior: Any behavior caused by or affecting another individual, usually of the same species.
Perinatal development and adult blood pressure. (1/205)
A growing body of evidence supports the concept of fetal programming in cardiovascular disease in man, which asserts that an insult experienced in utero exerts a long-term influence on cardiovascular function, leading to disease in adulthood. However, this hypothesis is not universally accepted, hence animal models may be of value in determining potential physiological mechanisms which could explain how fetal undernutrition results in cardiovascular disease in later life. This review describes two major animal models of cardiovascular programming, the in utero protein-restricted rat and the cross-fostered spontaneously hypertensive rat. In the former model, moderate maternal protein restriction during pregnancy induces an increase in offspring blood pressure of 20-30 mmHg. This hypertensive effect is mediated, in part, by fetal exposure to excess maternal glucocorticoids as a result of a deficiency in placental 11-ss hydroxysteroid dehydrogenase type 2. Furthermore, nephrogenesis is impaired in this model which, coupled with increased activity of the renin-angiotensin system, could also contribute to the greater blood pressure displayed by these animals. The second model discussed is the cross-fostered spontaneously hypertensive rat. Spontaneously hypertensive rats develop severe hypertension without external intervention; however, their adult blood pressure may be lowered by 20-30 mmHg by cross-fostering pups to a normotensive dam within the first two weeks of lactation. The mechanisms responsible for this antihypertensive effect are less clear, but may also involve altered renal function and down-regulation of the renin-angiotensin system. These two models clearly show that adult blood pressure is influenced by exposure to one of a number of stimuli during critical stages of perinatal development. (+info)Structural analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene in end-stage renal disease. (2/205)
BACKGROUND: Mutations in the 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) gene cause a rare form of low-renin hypertension leading to end-stage renal disease (ESRD) in some affected subjects. To date, no search for mutations in the HSD11B2 gene was performed in a large population to obtain an estimate its prevalence. METHODS: The HSD11B2 gene was analyzed in 587 subjects, including 260 ESRD patients (either dialysis or transplanted) for mutations in the exons 2 through 5 and corresponding intronic regions by polymerase chain reaction (PCR) using appropriate overlapping primers, gel analysis by single strand conformational polymorphism (SSCP), and sequencing of identified migration variants. RESULTS: The prevalence of single-nucleotide polymorphisms (SNPs) in ESRD patients and controls was 26%. The following genetic variants were found among all subjects investigated: exon 2 T442G (Leu148/Val, N = 70) and C470A (Thr156/Thr, N = 67), exon 3 G534A (Glu178/Glu, N = 69), and exon 5 C1274T (Asp388/Asp, N = 2). Four SNPs were identified in intron 4 only. In the control population, the prevalence of the variants Leu148 and Thr156 was 14% each. Glu178 was 11%, while no variants were found in exon 5. In ESRD patients, the prevalence of the variant Leu148 was 9%, and Thr156 was 8%. Glu178 was 13%, while the Asp388 variant was 0.7%. In patients with a short duration between the time of diagnosis of the renal disease and the onset of ESRD, the prevalence of the Leu148 and Glu178 variants was higher than in subjects with slowly progressing renal disease. The 11betaHSD2 activity of all of these SNPs is predictably unaltered. CONCLUSIONS: There is a high prevalence of SNPs of the HSD11B2 gene, without causing exonic mutations generating a 11betaHSD2 enzyme with altered activity. Based on statistical analyses, the frequency of homozygosity for mutated alleles of the HSD11B2 gene can be derived as <1/250,000 when a Caucasian population is considered. (+info)Multiple aspects of mineralocorticoid selectivity. (3/205)
Aldosterone regulates renal sodium reabsorption through binding to the mineralocorticoid receptor (MR). Because the glucocorticoid receptor (GR) is expressed together with the MR in aldosterone target cells, glucocorticoid hormones bound to GR may also intervene to modulate physiological functions in these cells. In addition, each steroid can bind both receptors, and the MR has equal affinity for aldosterone and glucocorticoid hormones. Several cellular and molecular mechanisms intervene to allow specific aldosterone regulatory effects, despite the large prevalence of glucocorticoid hormones in the plasma. They include the local metabolism of the glucocorticoid hormones into inactive derivatives by the enzyme 11beta-hydroxysteroid dehydrogenase; the intrinsic properties of the MR that discriminate between ligands through differential contacts; the possibility of forming homo- or heterodimers between MR and GR, leading to differential transactivation properties; and the interactions of MR and GR with other regulatory transcription factors. The relative contribution of each of these successive mechanisms may vary among aldosterone target cells (epithelial vs. nonepithelial) and according to the hormonal context. All these phenomena allow fine tuning of cellular functions depending on the degree of cooperation between corticosteroid hormones and other factors (hormonal or tissue specific). Such interactions may be altered in pathophysiological situations. (+info)Aldosterone receptor antagonism normalizes vascular function in liquorice-induced hypertension. (4/205)
The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) provides mineralocorticoid receptor specificity for aldosterone by metabolizing glucocorticoids to their receptor-inactive 11-dehydro derivatives. The present study investigated the effects of the aldosterone receptor antagonists spironolactone and eplerenone on endothelial function in liquorice-induced hypertension. Glycyrrhizic acid (GA), a recognized inhibitor of 11beta-HSD2, was supplemented to the drinking water (3 g/L) of Wistar-Kyoto rats over a period of 21 days. From days 8 to 21, spironolactone (5.8+/-0.6 mg. kg(-1). d(-1)), eplerenone (182+/-13 mg. kg(-1). d(-1)), or placebo was added to the chow (n=7 animals per group). Endothelium-dependent or -independent vascular function was assessed as the relaxation of preconstricted aortic rings to acetylcholine or sodium nitroprusside, respectively. In addition, aortic endothelial nitric oxide synthase (eNOS) protein content, nitrate tissue levels, and endothelin-1 (ET-1) protein levels were determined. GA increased systolic blood pressure from 142+/-8 to 185+/-9 mm Hg (P<0.01). In the GA group, endothelium-dependent relaxation was impaired compared with that in controls (73+/-6% versus 99+/-5%), whereas endothelium-independent relaxation remained unchanged. In the aortas of 11beta-HSD2-deficient rats, eNOS protein content and nitrate tissue levels decreased (1114+/-128 versus 518+/-77 microgram/g protein, P<0.05). In contrast, aortic ET-1 protein levels were enhanced by GA (308+/-38 versus 497+/-47 pg/mg tissue, P<0.05). Both spironolactone and eplerenone normalized blood pressure in animals on GA (142+/-9 and 143+/-9 mm Hg, respectively, versus 189+/-8 mm Hg in the placebo group; P<0.01), restored endothelium-dependent relaxation (96+/-3% and 97+/-3%, respectively, P<0.01 versus placebo), blunted the decrease in vascular eNOS protein content and nitrate tissue levels, and normalized vascular ET-1 levels. This is the first study to demonstrate that aldosterone receptor antagonism normalizes blood pressure, prevents upregulation of vascular ET-1, restores NO-mediated endothelial dysfunction, and thus, may advance as a novel and specific therapeutic approach in 11beta-HSD2-deficient hypertension. (+info)Expression of 11 beta-hydroxysteroid dehydrogenase isozymes and corticosteroid hormone receptors in primary cultures of human trophoblast and placental bed biopsies. (5/205)
Interconversion of active and inactive glucocorticoids, e.g. cortisol (F) and cortisone (E) is catalysed by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) which exists as two isoforms. We have used human placental bed biopsies and an in-vitro cytotrophoblast cell culture system to examine the expression and activity of the 11 beta-HSD isoforms along with that of the glucocorticoid and mineralocorticoid receptors (GR and MR). Immunohistochemistry localized 11 beta-HSD1 to decidualized stromal cells and 11 beta-HSD2 to villous cytotrophoblast, syncytiotrophoblasts and trophoblast cells invading the placental bed and maternal vasculature. In primary cultures of human cytotrophoblast, 11 beta-HSD2, GR and MR mRNA were expressed. Low levels of 11 beta-HSD1 mRNA were noted in these cultured cells, but could be explained on the basis of contaminating, vimentin-positive decidual stromal cells (< or =5%). Enzyme activity studies confirmed the presence of a high-affinity, NAD-dependent dehydrogenase activity (K(m) 137 nmol/l and V(max) 128 pmol E/h/mg protein), indicative of the 11 beta-HSD2 isoform. No reductase activity was observed. The presence of functional MR and GR was determined using Scatchard analyses of dexamethasone and aldosterone binding (MR K(d) 1.4 nmol/l B(max) 3.0; GR K(d) 6.6 nmol/l B(max) 16.2 fmol/ng protein). The expression of 11 beta-HSD1 in maternal decidua and 11 beta-HSD2 in adjacent trophoblast suggests an important role for glucocorticoids in determining trophoblast invasion. The presence of the MR within trophoblast indicates that some of the effects of cortisol could be MR- rather than GR-mediated. (+info)The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2. (6/205)
11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2 has been considered to protect the mineralocorticoid receptor (MR) by converting 11beta-hydroxyglucocorticoids into their inactive 11-keto forms, thereby providing specificity to the MR for aldosterone. To investigate the functional protection of the MR by 11beta-HSD2, we coexpressed epitope-tagged MR and 11beta-HSD2 in HEK-293 cells lacking 11beta-HSD2 activity and analyzed their subcellular localization by fluorescence microscopy. When expressed alone in the absence of hormones, the MR was both cytoplasmic and nuclear. However, when coexpressed with 11beta-HSD2, the MR displayed a reticular distribution pattern, suggesting association with 11beta-HSD2 at the endoplasmic reticulum membrane. The endoplasmic reticulum membrane localization of the MR was observed upon coexpression only with 11beta-HSD2, but not with 11beta-HSD1 or other steroid-metabolizing enzymes. Aldosterone induced rapid nuclear translocation of the MR, whereas moderate cortisol concentrations (10-200 nm) did not activate the receptor, due to 11beta-HSD2-dependent oxidation to cortisone. Compromised 11beta-HSD2 activity (due to genetic mutations, the presence of inhibitors, or saturating cortisol concentrations) led to cortisol-induced nuclear accumulation of the MR. Surprisingly, the 11beta-HSD2 product cortisone blocked the aldosterone-induced MR activation by a strictly 11beta-HSD2-dependent mechanism. Our results provide evidence that 11beta-HSD2, besides inactivating 11beta-hydroxyglucocorticoids, functionally interacts with the MR and directly regulates the magnitude of aldosterone-induced MR activation. (+info)Increased ACTH levels do not alter renal 11beta-hydroxysteroid dehydrogenase type 2 gene expression in the sheep. (7/205)
The regulation of renal 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) gene expression is poorly understood. Inhibition of expression can result in hypertension. An example of this is in ectopic adrenocorticotropin (ACTH) syndrome (EAS). Inhibition of 11betaHSD2 activity is suggested by the observed increased ratio of cortisol to cortisone in both plasma and urine. To investigate whether ACTH or ACTH-dependent steroids can modulate renal 11betaHSD2 gene expression we analysed renal 11betaHSD2 mRNA levels after treatment with ACTH of 1 H and 24 H and demonstrated no change in the levels of gene expression. We have demonstrated in this study that the expression of 11betaHSD2 in the kidney is unaltered by ACTH. The reduced inactivation of cortisol by 11betaHSD2 observed in EAS is likely to be in part due to end product inhibition or substrate overload of the enzyme by endogenous substrates (cortisol, corticosterone, etc) rather than inhibition of 11betaHSD2 at the transcriptional level by either ACTH or ACTH regulated steroids. (+info)Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation. (8/205)
BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. OBJECTIVE: To examine developmental changes in placental 11beta-HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In addition, there was a significant correlation between the two enzymes (r=0.58, P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11beta-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins. (+info)497 (2): 223-50. doi:10.1002/cne.20993. PMID 16705681. Shin, JW; Geerling, JC; Loewy, AD (Dec 10, 2008). "Inputs to the ... 26 (2): 411-7. doi:10.1523/JNEUROSCI.3115-05.2006. PMID 16407537. Geerling, JC; Loewy, AD (Oct 18, 2006). "Aldosterone- ... 93 (2): 177-209. doi:10.1113/expphysiol.2007.039891. PMID 17981930. Geerling, JC; Loewy, AD (Mar 2007). "Sodium depletion ... A small number of HSD2 neurons (less than 2%) may express the neuropeptide galanin. Their lack of expression of the ...
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 ...
1) Type B intercalated cells in the collecting duct reabsorb H+ and secrete HCO3. Protons are reabsorbed via both H+-K+ATPases ... These hormones and medications include insulin, epinephrine, and other beta agonists (e.g. salbutamol or salmeterol), 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 ...
2004). "11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics ... In type 2 diabetics aged 52-70, the drug improved verbal memory. However, potassium-sparing diuretic amiloride was co- ... 12 (2): 66-8. doi:10.5698/1535-7511-12.2.66. PMC 3316363 . PMID 22473546. Sandeep TC, Yau JL, MacLullich AM, et al. ( ... 11α-Hydroxyprogesterone Connors BW (2012). "Tales of a Dirty Drug: Carbenoxolone, Gap Junctions, and Seizures". Epilepsy Curr. ...
... type 3, rare (NIH) 3 beta hydroxysteroid dehydrogenase deficiency 3 hydroxyisobutyric aciduria 3 methylcrotonic aciduria 3 ... 17 alpha hydroxylase deficiency 17 beta hydroxysteroide dehydrogenase deficiency 17-beta-hydroxysteroid dehydrogenase ... 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 ... methylglutaconyl coa hydratase deficiency 3-hydroxy 3-methyl glutaryl-coa lyase deficiency 3-hydroxyacyl-coa dehydrogenase ...
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 ... "Human adrenal cortex and aldosterone secreting adenomas express both 11beta-hydroxysteroid dehydrogenase type 1 and 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 ...
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 ... 4-beta-glucosidase MeSH D08.811.277.450.420.200.600 --- glucan endo-1,3-beta-d-glucosidase MeSH D08.811.277.450.420.375 --- ... 20-hydroxysteroid dehydrogenases MeSH D08.811.682.047.436.400.074 --- 20alpha-hydroxysteroid dehydrogenase MeSH D08.811.682.047 ...
"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 ... "Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans". Diabetes. 58 (1): 46-53. doi: ... the endogenous type I and type II receptor agonist) or RU28362 (a specific type II receptor agonist) to adrenalectomized ...
Moghrabi N, Head JR, Andersson S (Nov 1997). "Cell type-specific expression of 17 beta-hydroxysteroid dehydrogenase type 2 in ... "The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species". DNA and Cell ... 17 beta-hydroxysteroid dehydrogenase type 2 in normal, inflamed and neoplastic gastric tissues". Anticancer Research. 23 (5A): ... "17 beta-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract". Clinical ...
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+ ...
"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: ...
... 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 ... 344 (2): 540-6. doi:10.1016/j.bbrc.2006.03.175. PMID 16630558. Dulos J, van der Vleuten MA, Kavelaars A, Heijnen CJ, Boots AM ( ... 121 (2): 307-14. doi:10.1016/S0306-4522(03)00438-X. PMID 14521990. Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, ...
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 ... "Entrez Gene: H6PD hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)". Tan SG, Ashton GC (1976). "An autosomal glucose- ... Beutler E, Morrison M (1968). "Localization and characteristics of hexose 6-phosphate dehydrogenase (glucose dehydrogenase)". J ...
"Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to ... 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 ... "Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1". ...
3(or 17)beta-hydroxysteroid dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular and ... 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 ... Mindnich R, Möller G, Adamski J (2004). "The role of 17 beta-hydroxysteroid dehydrogenases". Mol. Cell. Endocrinol. 218 (1-2): ...
Mindnich R, Möller G, Adamski J (2004). "The role of 17 beta-hydroxysteroid dehydrogenases". Mol. Cell. Endocrinol. 218 (1-2): ... Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in ... 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 ... Aldo-keto reductase family 1 member C3 (AKR1C3), also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a ... "Entrez Gene: AKR1C3 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II)". Tian Y, Zhao L, ...
... 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 ...
Pancreatic beta cells are responsible for making insulin; decreased beta cell activity is associated with DM2 in adulthood. In ... However, one common challenge of these types of studies is that many epigenetic modifications have tissue and cell-type ... When analyzing the types of changes that can occur to a phenotype, we can see changes that are behavioral, morphological, or ... This syndrome is often associated with type II diabetes as well as hypertension and atherosclerosis. Using mice models, ...
"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 ...
Weizmann Institute of Science > GeneCards > hydroxysteroid (11-beta) dehydrogenase 2 Archived June 2, 2011, at the Wayback ... Liquorice consumption may also cause a temporary form of AME due to its ability to block 11β-hydroxysteroid dehydrogenase type ... It results from mutations in the HSD11B2 gene, which encodes the kidney isozyme of 11β-hydroxysteroid dehydrogenase type 2. In ... Inborn errors of steroid metabolism 11β-Hydroxylase I deficiency Hyperaldosteronism Pseudohyperaldosteronism Glucocorticoid- ...
... 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- ...
... adrenal hyperplasia due to 21-hydroxylase deficiency Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase ... Tooth disease type 1C Charcot-Marie-Tooth disease type 2A Charcot-Marie-Tooth disease type 2B1 Charcot-Marie-Tooth disease type ... Ccge syndrome CCHS CDG syndrome type 1A CDG syndrome type 1B CDG syndrome type 1C CDG syndrome type 2 CDG syndrome type 3 CDG ... disease type 2C Charcot-Marie-Tooth disease type 2D Charcot-Marie-Tooth disease type 4A Charcot-Marie-Tooth disease type 4B ...
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, ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... 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 ... Sun T, Han X (2019). "Death versus dedifferentiation: The molecular bases of beta cell mass reduction in type 2 diabetes". ... Type 1 and type 2 diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and ...
H. Zhu, C. Zou, X. Fan et al., "Upregulation of 11beta-hydroxysteroid dehydrogenase type 2 expression by Hedgehog ligand ... β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression in human trophoblast cells through modulation of 11β-HSD2 messenger ... β-hydroxysteroid dehydrogenase type 2 in preeclamptic placentas is associated with decreased PPARγ but increased PPARα ... β-hydroxysteroid dehydrogenase type 2 expression," Journal of Clinical Investigation, vol. 114, no. 8, pp. 1146-1157, 2004. ...
11-Beta-Hydroxysteroid Dehydrogenase Type 2 Recombinant Protein-AAC50356.1 (MBS2031421) product datasheet at MyBioSource, ... Belongs to the short-chain dehydrogenases/reductases (SDR) family.. Protein type: Oxidoreductase; Lipid Metabolism - C21- ... The type II isozyme, encoded by this gene, has only 11-beta-dehydrogenase activity. In aldosterone-selective epithelial tissues ... The type I isozyme has both 11-beta-dehydrogenase (cortisol to cortisone) and 11-oxoreductase (cortisone to cortisol) ...
Structural analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene in end-stage renal disease. Kidney Int. 2000;58:1413 ... Molecular basis of human salt sensitivity: the role of the 11beta-hydroxysteroid dehydrogenase type 2. J Clin Endocrinol Metab ... Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2. J Clin Invest. 1999;103:683-689. ... In vivo footprinting of the human 11beta-hydroxysteroid dehydrogenase type 2 promoter: evidence for cell-specific regulation by ...
... has both dehydrogenase (11 beta DH) and reductase (11 beta R) activities, which catalyse the interconversion of cortisol and ... 11beta hydroxysteroid dehydrogenase type 2. 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) has both dehydrogenase (11 beta ... Using radiolabelled cortisol 11 beta HSD activity has been shown to be lower in some cases of essential hypertension. This ... This approach was evaluated by inducing partial deficiency of 11 beta HSD in the volunteers who took liquorice (to inhibit 11 ...
Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ... The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby ... Association between a variant in the 11 beta-hydroxysteroid dehydrogenase type 2 gene and primary hypertension.. Melander O1, ... 2) = 11.0, df = 10; P = 0.36). In conclusion, over-representation of individuals homozygous for the G534 allele in hypertensive ...
Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent ... Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes ... frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 ... 150 patients with type 1 diabetes and nephropathy (DN), 145 patients with type 1 diabetes with a long duration of non- ...
Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102-110pmid:12502499. ... Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol ... 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: ...
497 (2): 223-50. doi:10.1002/cne.20993. PMID 16705681. Shin, JW; Geerling, JC; Loewy, AD (Dec 10, 2008). "Inputs to the ... 26 (2): 411-7. doi:10.1523/JNEUROSCI.3115-05.2006. PMID 16407537. Geerling, JC; Loewy, AD (Oct 18, 2006). "Aldosterone- ... 93 (2): 177-209. doi:10.1113/expphysiol.2007.039891. PMID 17981930. Geerling, JC; Loewy, AD (Mar 2007). "Sodium depletion ... A small number of HSD2 neurons (less than 2%) may express the neuropeptide galanin. Their lack of expression of the ...
Analysis of the 11beta-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) in human essential hypertension. Am J Hypertens 2005 ... Epigenetic modulation of the renal beta-adrenergic-WNK4 pathway in salt-sensitive hypertension. Nat Med 2011; 17 (5): 573-580. ... deoxycytidine stimulates sACE mRNA expression specifically in in vitro cell type and in vivo tissue type.26 5-Aza-2′- ... Zhang YC, Bui JD, Shen L, Phillips MI . Antisense inhibition of beta(1)-adrenergic receptor mRNA in a single dose produces a ...
The type II isozyme, encoded by this gene, has only 11-beta-dehydrogenase activity. In aldosterone-selective epithelial tissues ... The type I isozyme has both 11-beta-dehydrogenase (cortisol to cortisone) and 11-oxoreductase (cortisone to cortisol) ... such as the kidney, the type II isozyme catalyzes the glucocorticoid cortisol to the inactive metabolite cortisone, thus ... There are at least two isozymes of the corticosteroid 11-beta-dehydrogenase, a microsomal enzyme complex responsible for the ...
Reduced placental 11β-HSD2 in human pregnancy correlates with lower birth weight and higher blood pressure in later life. ... Reduced placental 11β-HSD2 in human pregnancy correlates with lower birth weight and higher blood pressure in later life. ... Similarly, in animal models, inhibition or knockout of placental 11β-HSD2 lowers offspring birth weight, in part by reducing ... Similarly, in animal models, inhibition or knockout of placental 11β-HSD2 lowers offspring birth weight, in part by reducing ...
By product type. Primary antibodies. Secondary antibodies. ELISA and Matched Antibody Pair Kits. Cell and tissue imaging tools ... Belongs to the short-chain dehydrogenases/reductases (SDR) family.. * Cellular localization. Microsome. Endoplasmic reticulum. ... Hydroxysteroid 11 beta dehydrogenase isoenzyme 2 antibody. *NAD dependent 11 beta hydroxysteroid dehydrogenase antibody ... By product type. Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex ...
... peroxides osteocalcin bone isoenzyme of alkaline phosphatase ascorbic acid IGF-1 IGFBP-3 beta-carotene ... 2. Contents 1. 서론 4. 태아에 대한 영향 2. 병리과정 5. 금연 3. 산모에 대한 영향 6. 결론 ... 11. enzymatic activity 병리과정 • Tobacco usage alter mitochondrial respiratory function in cardiomyocytes and lung tissue. • ... By contrast, most placental zinc remains unbound to MTs • MT-2 isoform(induced by smoking ) could be involved in placental ...
Organotins disrupt the 11beta-hydroxysteroid dehydrogenase type 2-dependent local inactivation of glucocorticoids. Environ ... Arsenic induces pancreatic beta-cell apoptosis via the oxidative stress-regulated mitochondria-dependent and endoplasmic ... type" and "brain-type" glucose transporters in mice. Mol Pharmacol 1995;47:65-73. ... Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study). Diabetes Care ...
17 beta-hydroxysteroid dehydrogenases reveal a remarkable multifunctionality being able to modulate concentrations not only of ... Dysfunctions in human 17 beta-hydroxysteroid dehydrogenases result in disorders of biology of reproduction and neuronal ... 17 beta -HSD). The latter are present in many microorganisms, invertebrates and vertebrates. ... The biological activity of steroid hormones is regulated at the pre-receptor level by several enzymes including 17 beta- ...
Blue cells = expressed in wild-type.. Gray triangles = other expression annotations only. (e.g. absence of expression or data ... Survivors are subject to sudden unexplained deaths when between 2 and 4 months of age. They are hypertensive with dilute urine ... 1 human;1 mouse;1 rat;1 chimpanzee;1 cattle;1 dog;2 chicken;1 zebrafish;1 frog, western clawed;1 macaque, rhesus. ... J:29215 Cole TJ, Cloning of the mouse 11 beta-hydroxysteroid dehydrogenase type 2 gene: tissue specific expression and ...
Type: Journal Article; Research Support, Non-U.S. Govt; Review Date: 2012-09-19. ... 0/Glucocorticoids; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2 From MEDLINE®/PubMed®, a database of the U.S. ... 11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors, physiology. Adaptation, Physiological. Adult. Animals. ... CZB/4/582//Chief Scientist Office; CZG/2/478//Chief Scientist Office; //Wellcome Trust ...
cortisol 11-beta-ketoreductase deficiency. 11-beta-hydroxysteroid dehydrogenase deficiency type 2 ...
2004) 11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. J Clin ... 2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11:191-198. ... 2001) Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action. ... and glucose tolerance in 11beta-hydroxysteroid dehydrogenase type 1 null mice. J Biol Chem 276:41293-41300. ...
Distal tubular electrolyte transport during inhibition of renal 11beta-hydroxysteroid dehydrogenase. Am. J. Physiol. Renal ... 2008). Angiotensin type 1 receptors in the subfornical organ mediate the drinking and hypothalamic-pituitary-adrenal response ... Brain serotoninergic stimulation reduces the water intake induced by systemic and central beta-adrenergic administration. Braz ... Yang, G., Xi, Z. X., Wan, Y., Wang, H., and Bi, G. (1993). Changes in circulating and tissue angiotensin II during acute and ...
Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The ... 2, 42-46.. Herrera, E, Lasuncion, MA, Gomes Coronado, D, Aranda, P, Lopez-Luna, P & Maier, I (1988) Role of lipoprotein lipase ... Semin Perinatol 2, 223-234.. Ozanne, SE, Martensz, ND, Petry, CJ, Loizou, CL & Hales, CN (1998) Maternal low protein diet in ... Cells Tissues Organs 164, 2-13.. Kaijser, M, Granath, F, Jacosen, G, Cnattingius, S & Ekbom, A (2000) Maternal pregnancy ...
Tiwari, A. (2010). INCB-13739, an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor for the treatment of type 2 diabetes. ... 1993). Altered ratios of beta-endorphin: Beta-lipotropin released from anterior lobe corticotropes with increased secretory ... 2004). Cell-type specific calcium signaling by corticotropin-releasing factor type 1 (CRF1) and 2a (CRF2(a)) receptors: ... 1993). A C-Elegans mutant that lives twice as long as wild-type. Nature, 366(6454), 461-464.PubMedCrossRefGoogle Scholar ...
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 ...
... renin ratio is increased slightly by beta blockers, clonidine, nonsteroidal anti-inflammatory agents, renin inhibitors, and ... Cancer Types. Open Submenu. * Cancer Types. Back. *Brain Cancer. *Breast Cancer. *Cervical Cancer ... Measurement of the ratio of cortisol to cortisone serves as an indicator of whether there is decreased activity of the 11-beta- ... hydroxysteroid dehydrogenase 2. (Table 1) Table 1.. Plasma Aldosterone. Serum Potassium. Plasma Renin. ...
Chrousos GP: Is 11beta-hydroxysteroid dehydrogenase type 1 a good therapeutic target for blockade of glucocorticoid actions?. ... Delaunay F, Khan A, Cintra A, Davani B, Ling ZC, Andersson A, Ostenson CG, Gustafsson J, Efendic S, Okret S: Pancreatic beta ... Murphy VE, Zakar T, Smith R, Giles WB, Gibson PG, Clifton VL: Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is ... Cai TQ, Wong B, Mundt SS, Thieringer R, Wright SD, Hermanowski-Vosatka A: Induction of 11beta-hydroxysteroid dehydrogenase type ...
GlucocorticoidCortisol to cortisoneInhibitionHSD11B2Enzyme 11CarbenoxoloneReductaseInhibitorCortisone to cortisolInhibitors of 11Placental 11EndocrinologyIsoformsMetabolismProteinAntibodyEpithelialCorticosteroidReceptorsGenesHydrocortisoneTissue-specificDiabetes mellitusAldosteroneDexamethasoneEnzymesAdultVivoMiceAssayDysregulationMaternalInsulin secretionDiseasesMolecularRenalInhibitsReceptorObesitySecretionCushingoid
- The glucocorticoid hypothesis is affirmed by studies that have shown that elevated maternal cortisol is associated with heightened HPA activity [ 2 ] and alterations in brain structure [ 3 ] in affected offspring. (hindawi.com)
- Glucocorticoid hormones potently regulate metabolism and, in rare cases of excess (Cushing syndrome), cause metabolic syndrome ( 2 ). (diabetesjournals.org)
- Elevated local tissue glucocorticoid excess, driven by increased levels of the intracellular glucocorticoid regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), particularly in adipose tissue, is implicated in the development of idiopathic metabolic syndrome ( 3 ). (diabetesjournals.org)
- In aldosterone-selective epithelial tissues such as the kidney, the type II isozyme catalyzes the glucocorticoid cortisol to the inactive metabolite cortisone, thus preventing illicit activation of the mineralocorticoid receptor. (creativebiomart.net)
- Here we present data to demonstrate that the adverse side-effect profile associated with exogenous active glucocorticoid (GC) administration (including glucose intolerance, hyperinsulinemia, hypertension, hepatic steatosis, increased adiposity, and myopathy) is prevented by global deletion of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in mice. (pnas.org)
- Carbenoxolone may decrease the amount of active glucocortocoid in the brain, because the drug inhibits 11β-HSD, an enzyme which regenerates cortisol , an active glucocorticoid, from inactive cortisone . (wikidoc.org)
- Phenylethanolamine N-methyltransferase gene expression: synergistic activation by Egr-1, AP-2 and the glucocorticoid receptor. (naver.com)
- Expression of genes encoding for corticotropin-releasing hormone (CRH), CRH receptors (CRHR) 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC), melanocortin receptor 2 (MC2R), and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD) 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. (biomedcentral.com)
- On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1). (biomedcentral.com)
- Key molecules mediating and regulating tissue-specific glucocorticoid actions are 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 isozymes, both of which are expressed in the placenta and the fetal membranes. (ox.ac.uk)
- 11-b-hydroxysteroid dehydrogenase (11b-HSD) is a microsomal short chain dehydrogenase/reductase (SDR) which catalyzes the inter-conversion of biologically active glucocorticoid (cortisol in human and corticosterone in rats and mice) and inactive glucocorticoid (cortisone and 11-dehydrocorticosterone). (mybiosource.com)
- The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocorticoid receptor from the mineralocorticoid actions of cortisol. (cdc.gov)
- The type I isozyme has both 11-beta-dehydrogenase (cortisol to cortisone) and 11-oxoreductase (cortisone to cortisol) activities. (creativebiomart.net)
- The active agent in licorice, glycyrrhizin, inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol to cortisone in the kidney. (oncologynurseadvisor.com)
- Measurement of the ratio of cortisol to cortisone serves as an indicator of whether there is decreased activity of the 11-beta-hydroxysteroid dehydrogenase 2. (oncologynurseadvisor.com)
- We find that pan-, class I, or class IIa HDAC inhibition promoted 11 β -HSD2 expression and prevented cortisol or interleukin-1 β -induced decrease in its expression. (hindawi.com)
- Inhibition of the mitogen-activated protein kinases (MAPK) ERK1/2 increases HSD11B2 expression [ 12 ], whilst suppressing p38 reduces 11 β -HSD2 activity [ 13 ]. (hindawi.com)
- Similarly, in animal models, inhibition or knockout of placental 11β-HSD2 lowers offspring birth weight, in part by reducing glucose delivery to the developing fetus in late gestation. (frontiersin.org)
- Because of its inhibition of 11β-HSD and consequent potentiation of corticosteroids, 11α-OHP has recently been patented for the treatment of skin diseases, particularly psoriasis in combination with clobetasol propionate and minoxidil. (wikipedia.org)
- These data challenge our current view of GC action, demonstrating 11β-HSD1, particularly in adipose tissue, is key to the development of the adverse metabolic profile associated with circulating GC excess, offering 11β-HSD1 inhibition as a previously unidentified approach to treat Cushing syndrome. (pnas.org)
- 2004). "11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics" . (wikidoc.org)
- Chemical inhibition of myristoylation of the G-protein Gi1 alpha by 2-hydroxymyristate does not interfere with its palmitoylation or membrane association. (naver.com)
- Prolonged treatment with dexamethasone also increased the enzyme activity of 11β-HSD in the cells in a dose- and time-dependent manner, with complete inhibition by RU38486. (elsevier.com)
- The mechanism of the variable and distinct 11β-hydroxysteroid dehydrogenase type 2 gene ( HSD11B2 ) expression in the cortical collecting duct is poorly understood. (ahajournals.org)
- Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nep. (cdc.gov)
- Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent mineralocorticoid excess where cortisol acts as a mineralocorticoid. (cdc.gov)
- Weak associations are reported between the HSD11B2 gene, type 1 diabetes mellitus and nephropathy. (cdc.gov)
- The increased frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and may, in part, explain the enhanced salt sensitivity observed in patients with type 1 diabetes. (cdc.gov)
- The HSD11B2 gene, encoding the kidney isoenzyme 11β-hydroxysteroid dehydrogenase, is a candidate for essential hypertension. (nature.com)
- HSD11B2 has several biochemical functions, for example, 11-beta-hydroxysteroid dehydrogenase [NAD(P)] activity, NAD binding, steroid binding. (creativebiomart.net)
- At the core of this process is the placental enzyme 11 β -hydroxysteroid dehydrogenase type 2 (11 β -HSD2), an enzyme that is expressed primarily within the syncytiotrophoblast of the placenta where it catalyses the conversion of active cortisol into its inactive product cortisone, thereby controlling the levels of cortisol that reach the fetus [ 4 ]. (hindawi.com)
- The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is selectively expressed in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor. (ahajournals.org)
- 16 The enzyme 11βHSD type 2 (11βHSD2) isoform binds NAD with high affinity and catalyzes the dehydrogenation of 11β-hydroxyglucocorticoids. (nature.com)
- The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). (medworm.com)
- Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. (springer.com)
- Carbenoxolone reversibly inhibits the conversion of cortisol to the inactive metabolite cortisone by blocking 11β-hydroxysteroid dehydrogenase (11β-HSD). (wikidoc.org)
- We examined whether carbenoxolone, a potent inhibitor of 11β-HSD, would potentiate the inhibitory action of dexamethasone on interleukin-8 release from BEAS-2B cells, and whether prolonged treatment with dexamethasone at therapeutic doses would upregulate 11β-HSD2 in the cells. (elsevier.com)
- 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. (stoynev.us)
- Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II. (wikipathways.org)
- Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1. (wikipathways.org)
- Markers of 11β-hydroxysteroid dehydrogenase type 1 activity increased from the age of 3 months as did those of 5α-reductase activity. (ox.ac.uk)
- In 1995, 11α-OHP, along with its epimer 11β-hydroxyprogesterone, was identified as a very potent competitive inhibitor of both isoforms (1 and 2) of 11β-hydroxysteroid dehydrogenase (11β-HSD). (wikipedia.org)
- 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 than was glycyrrhetinic acid (GA) (approximate IC50 = 0.9 vs. 15 nM). (wikipedia.org)
- In intact cells 11α-hydroxyprogesterone is a more potent inhibitor of 11β-HSD1 than glycyrrhetinic acid or 11β-hydroxyprogesterone (117, 118). (wikipedia.org)
- It is an orally available small molecule inhibitor of 11beta-HSD1 (11-beta hydroxysteroid dehydrogenase type 1). (drugbank.ca)
- 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that, in the presence of the NADPH-generating enzyme H6PDH, primarily activates GCs (cortisone to cortisol in humans, 11-dehydrocorticosterone to corticosterone in mice) in vivo and determines their tissue-specific exposure [ 15 ]. (biomedcentral.com)
- This raises the intriguing possibility that therapeutic inhibitors of 11β-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids. (biomedcentral.com)
- Placental 11 β -HSD2 is known to be reduced in a number of adverse pregnancy complications, possibly through an epigenetic mechanism. (hindawi.com)
- Reduced placental 11β-HSD2 in human pregnancy correlates with lower birth weight and higher blood pressure in later life. (frontiersin.org)
- Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2. (naver.com)
- 2 Endocrinology Unit, University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, U.K. (diabetesjournals.org)
- The P450 arachidonic acid monooxygenases oxidize arachidonic acid to a) 19- or 20-HETE (w-hydroxylase or CYP4 isoforms), or b) 5,6-, 8,9-, 11,12-, or 14,15-EET (epoxygenase or CYP2 isoforms). (herokuapp.com)
- Androgen metabolism via 17beta-hydroxysteroid dehydrogenase type 3 in mammalian and non-mammalian vertebrates: comparison of the human and the zebrafish enzyme. (wikipathways.org)
- One possible factor is a regulated increase in the movement of cytoplasmic protein to the luminal membrane leading to a restoration of functional transporter to an essentially wild type level. (bio5.org)
- Quantitative, real-time RT-PCR measurements confirmed increases seen for six selected transcripts (Wilms' tumor protein, beta-arrestin 2, neurofibromin, casein kinase IIbeta, aquaporin-3, and aquaporin-4). (bio5.org)
- For several targets including aquaporin-2, transcript abundance and protein abundance changes did not correlate. (bio5.org)
- Targets with demonstrated increases in both protein and mRNA abundances included neurofibromin, casein kinase IIbeta, the beta-subunit of the epithelial Na channel (beta-ENaC), 11beta-hydroxysteroid dehydrogenase type 2, and c-Fos. (bio5.org)
- When the cells were incubated with dexamethasone for up to 72 hours at increasing concentrations (10 -9 to 10 -5 M), there were considerable increases in mRNA and protein levels of 11β-HSD2. (elsevier.com)
- 11bHSD-2 (rat 400-aa, mouse 396-aa, human 405-aa) is a ~41kD glycosylated membrane-protein present in the endoplasmic reticulum (ER). (mybiosource.com)
- The microtiter plate provided in this kit has been pre-coated with an antibody specific to 11-Beta-Hydroxysteroid Dehydrogenase Type 3 (HSD11b3). (sinoprot.com)
- Standards or samples are then added to the appropriate microtiter plate wells with a biotin-conjugated antibody specific to 11-Beta-Hydroxysteroid Dehydrogenase Type 3 (HSD11b3). (sinoprot.com)
- After TMB substrate solution is added, only those wells that contain 11-Beta-Hydroxysteroid Dehydrogenase Type 3 (HSD11b3), biotin-conjugated antibody and enzyme-conjugated Avidin will exhibit a change in color. (sinoprot.com)
- There was no difference in the mRNA expressions of thiazide-sensitive NaCl cotransporter, epithelial Na channel (ENaC), aquaporin-2, ROMK, and NaKATPase. (bio5.org)
- There are at least two isozymes of the corticosteroid 11-beta-dehydrogenase, a microsomal enzyme complex responsible for the interconversion of cortisol and cortisone. (creativebiomart.net)
- In plain Ingrish, this means that estrogen helps pesky fat-mongering A-2 receptors do their work, and there are three effective gambits for losing fat despite this. (tim.blog)
- Bord S, Horner A, Beavan S, Compston J. Estrogen receptors alpha and beta are differentially expressed in developing human bone. (labome.org)
- Of the 1,176 genes on the array, 137 transcripts were increased by 2-fold or more, and 10 transcripts were decreased to 0.5-fold or less. (bio5.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)
- In immortalized B-cells derived from 95 asthmatics and their unaffected siblings, 12 of the 38 (31.6%) vitamin D pathway lung development genes were significantly differentially expressed (OR 3.00, 95% CI: 1.43-6.21), whereas 11 (29%) genes were significantly differentially expressed in 43 control versus vitamin D treated immortalized B-cells from Childhood Asthma Management Program subjects (OR 2.62, 95% CI: 1.22-5.50). (biomedcentral.com)
- Plasma steroid kinetics were investigated following oral hydrocortisone (a substrate for 11 beta DH) and prednisone (a substrate for 11 beta R) in five normotensive volunteers after dexamethasone suppression of endogenous steroid production. (stoynev.us)
- 11α-OHP is used as a precursor in chemical syntheses of cortisone and hydrocortisone. (wikipedia.org)
- The potential association of 11beta-HSD1 tissue-specific dysregulation with gestational diabetes, as well as the plausible utility of 11beta-HSD2, as a biomarker of pregnancy adversity and later life morbidity, are emerging areas of intense scientific interest and future investigation. (ox.ac.uk)
- 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. (biomedcentral.com)
- although the morbidity and mortality rates for countless diseases have been reduced due to advances in medical research and high standard of living, the rate of type 2 diabetes mellitus increases. (kon.org)
- Investigated for use/treatment in diabetes mellitus type 2 and diabetes prevention. (drugbank.ca)
- The aldosterone:renin ratio is increased slightly by beta blockers, clonidine, nonsteroidal anti-inflammatory agents, renin inhibitors, and renal impairment, possibly leading to false-positive results for the screening test. (oncologynurseadvisor.com)
- It has also been suggested that angiotensin receptor type 1 (AT1) also participates in the aldosterone-induced rapid effects. (springermedizin.de)
- and (2) critically address the controversial points within the literature as regarding which receptor participates in the rapid pathway display by aldosterone. (springermedizin.de)
- Krozowski, Zygmund S. / Dexamethasone upregulates 11β-hydroxysteroid dehydrogenase type 2 in BEAS-2B cells . (elsevier.com)
- The biological activity of steroid hormones is regulated at the pre-receptor level by several enzymes including 17 beta-hydroxysteroid dehydrogenases (17 beta -HSD). (semanticscholar.org)
- 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. (semanticscholar.org)
- In the United States, more than 30% of the adult population is obese, and some studies estimate that by 2030, more than 366 million people worldwide will develop type 2 diabetes, with obesity being an important factor responsible for this increase ( 8 , 9 ). (pnas.org)
- 11 Beta-hydroxysteroid dehydrogenase type 2 in the postnatal and adult rat brain. (naver.com)
- This study investigated a novel approach to estimating 11 beta HSD activity in vivo. (stoynev.us)
- It may therefore be applied to the measurement of 11 beta HSD activity in vivo in large numbers of hypertensive patients without the use of radioisotopes. (stoynev.us)
- 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 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)
- To define the direct impact of elevated pancreatic β-cell 11β-HSD1 on insulin secretion, we generated β-cell-specific, 11β-HSD1-overexpressing (MIP-HSD1) mice on a strain background prone to β-cell failure. (diabetesjournals.org)
- 11β-HSD1 −/− mice showed mild β-cell impairment that was offset by improved glucose tolerance. (diabetesjournals.org)
- The benefit of higher β-cell 11β-HSD1 exhibited a threshold because homozygous MIP-HSD1 tg/tg mice and diabetic Lep db/db mice with markedly elevated β-cell 11β-HSD1 levels had impaired basal β-cell function. (diabetesjournals.org)
- This premise is strongly supported by the phenotype of transgenic mice overexpressing 11β-HSD1 in fat or liver, which recapitulates diabetes and insulin-resistant metabolic disease, and by the protection from metabolic disease exhibited by 11β-HSD1 −/− mice ( 3 ). (diabetesjournals.org)
- 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)
- Whereas liver-specific 11β-HSD1 KO mice developed a full Cushingoid phenotype, adipose-specific 11β-HSD1 KO mice were protected from hepatic steatosis and circulating fatty acid excess. (pnas.org)
- 2. p47(phox) contributes to albuminuria and kidney fibrosis in mice. (herokuapp.com)
- Wild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). (biomedcentral.com)
- Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. (biomedcentral.com)
- In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone. (biomedcentral.com)
- This assay has high sensitivity and excellent specificity for detection of 11-Beta-Hydroxysteroid Dehydrogenase Type 3 (HSD11b3). (sinoprot.com)
- Intra-assay Precision (Precision within an assay): 3 samples with low, middle and high level 11-Beta-Hydroxysteroid Dehydrogenase Type 3 (HSD11b3) were tested 24 times on one plate, respectively. (sinoprot.com)
- Inter-assay Precision (Precision between assays): 3 samples with low, middle and high level 11-Beta-Hydroxysteroid Dehydrogenase Type 3 (HSD11b3) were tested on 3 different plates, 8 replicates in each plate. (sinoprot.com)
- An enzyme activity assay of the cell homogenate demonstrated only NAD + -dependent dehydrogenase activity. (elsevier.com)
- Dysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond. (ox.ac.uk)
- 11beta-HSD1 is implicated in the pathogenesis of metabolic syndrome and its dysregulation has been observed in pregnancy-related complications (pre-eclampsia, intrauterine growth restriction). (ox.ac.uk)
- The fetal origins or Barker [ 11 ] hypothesis states that in utero exposure to the maternal environment, including diet, may influence the eventual development of chronic disease. (biomedcentral.com)
- Elevated 11β-HSD1 is also found in pancreatic islets of obese/diabetic rodents and is hypothesized to suppress insulin secretion and promote diabetes. (diabetesjournals.org)
- Type 2 Diabetes develops through abnormal insulin action and insulin secretion (Goldstein, 2002). (kon.org)
- Despite the potential importance of EDCs in the pathogenesis of metabolic diseases, the contribution of synthetic chemical exposure to the diabetes epidemic remains largely unrecognized and underappreciated even though U.S. diabetes rates have increased in concordance with the national production of synthetic organic chemicals ( Fig. 2 ). (diabetesjournals.org)
- Although dietary energy restriction can increase the maximum lifespan of laboratory animals and is therefore hailed as an "antiaging" intervention ( 10 ), its major effect is to increase the average lifespan by preventing or delaying the development of various diseases that are the primary cause of death in overweight rodents ( 11 ). (pnas.org)
- 11α-Hydroxyprogesterone can therefore influence blood pressure regulation.12 Furthermore, 11α-hydroxyprogesterone exhibits an anti-androgenic activity with minimal estrogenic and progestational side effects.13 This substance was also recently patented for its role in treating skin diseases, especially for psoriasis in combination with clobetasol propionate and minoxidil.14. (wikipedia.org)
- There is an epidemic in children of metabolic syndrome, obesity, type 2 diabetes and other individual diseases that form the components of metabolic syndrome. (eurekaselect.com)
- This study not only defines a significant shift in our understanding of the physiological and molecular mechanisms underpinning the adverse side effects associated with GC use but also raises the possibility of targeting 11β-HSD1 as a novel adjunctive therapy in the treatment of Cushing syndrome. (pnas.org)
- Duration of type 1 diabetes, diabetic status and renal function were recorded. (cdc.gov)
- INCB13739 inhibits 11beta-HSD1 and has the potential to provide a broad spectrum impact on the multiple components seen in patients with type 2 diabetes. (drugbank.ca)
- INCB13739 completely inhibits the production of intra-adipose and intra-hepatic cortisol by 11beta-HSD1, while maintaining normal systemic cortisol levels, which are essential for immune function and response to stress. (drugbank.ca)
- It seemed that one answer would be a topical lotion that inhibits the A-2 receptor or blocks phosphodiesterase (1). (tim.blog)
- Spatial and temporal expression of alpha- and beta-thyroid hormone receptor mRNAs, including the beta 2-subtype, in the developing mammalian nervous system. (springer.com)
- Unilateral labyrinthectomy downregulates glutamate receptor delta-2 expression in the rat vestibulocerebellum. (naver.com)
- The A-2 receptor, or alpha-2 andrenergic receptor, is the party spoiler when it comes to fat-loss in gender-specific problem areas. (tim.blog)
- Type 2 diabetes prevalence has risen dramatically in parallel with the worldwide increase in obesity ( 1 ). (diabetesjournals.org)
- 2014). In addition, the melanocortin system's influence on circulating glucose levels suggests it could also be targeted to treat obesity-related type 2 diabetes (Morgan et al. (springer.com)
- This paper is a review of the role of cortisol and abdominal obesity in the epidemic of type 2 Diabetes. (kon.org)
- Future efforts in this related struggle against both obesity and type 2 diabetes should encompass a strong focus on cortisol so such prevention and treatment can successfully advance. (kon.org)
- Abdominal obesity has been strongly correlated with insulin resistance and type 2 diabetes, and cortisol may be involved (Franco, 2001). (kon.org)
- Poor diet and low exercise can not explain many facets of the epidemic including the onset in children 6 month of age, the protective effect of obesity on the incidence of type 1 diabetes and the epidemic of type 2 diabetes/metabolic syndrome in grass fed horses. (eurekaselect.com)
- Data from Italy confirmed an inverse association between obesity and type 1 diabetes. (eurekaselect.com)
- Further studies indicate the inverse relationship between type 1 diabetes and type 2 diabetes/obesity is due to cortisol production. (eurekaselect.com)
- Data indicates those with low cortisol responses have a predilection for type 1 diabetes and other autoimmune disorders following inflammation, while those with high cortisol/ immune suppressive responses develop type 2 diabetes/metabolic syndrome/obesity which resembles a Cushingoid state but are spared in the autoimmune disorders. (eurekaselect.com)
- Finally, there is a strong mechanism data that macrophage produced interleukin 1, tumor necrosis factor and interleukin 6, which are released following inflammation, causing destruction of insulin secreting islet cells and increase cortisol release, and thus have the ability to cause both type 1 and type 2 diabetes/metabolic syndrome (which resembles a Cushingoid state). (eurekaselect.com)