A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of molecular oxygen and NADPH-specific flavoprotein. This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE.
A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
A mitochondrial cytochrome P450 enzyme that catalyzes the 11-beta-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11B1 gene, is important in the synthesis of CORTICOSTERONE and HYDROCORTISONE. Defects in CYP11B1 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
A congenital or acquired condition of insufficient production of ALDOSTERONE by the ADRENAL CORTEX leading to diminished aldosterone-mediated synthesis of Na(+)-K(+)-EXCHANGING ATPASE in renal tubular cells. Clinical symptoms include HYPERKALEMIA, sodium-wasting, HYPOTENSION, and sometimes metabolic ACIDOSIS.
A condition caused by the overproduction of ALDOSTERONE. It is characterized by sodium retention and potassium excretion with resultant HYPERTENSION and HYPOKALEMIA.
11 beta,18,21-Trihydroxypregn-4-ene-3,20-dione.
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.
Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.
A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.
The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.
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.
The narrow subcapsular outer zone of the adrenal cortex. This zone produces a series of enzymes that convert PREGNENOLONE to ALDOSTERONE. The final steps involve three successive oxidations by CYTOCHROME P-450 CYP11B2.
A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM.
A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.
Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
An orphan nuclear receptor that is found at high levels in BRAIN tissue. The protein is believed to play a role in development and maintenance of NEURONS, particularly dopaminergic neurons.
An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver and secreted into blood circulation. Angiotensinogen is the inactive precursor of natural angiotensins. Upon successive enzyme cleavages, angiotensinogen yields angiotensin I, II, and III with amino acids numbered at 10, 8, and 7, respectively.
An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).
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.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Enzyme that catalyzes the first step of the tricarboxylic acid cycle (CITRIC ACID CYCLE). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme A. This enzyme was formerly listed as EC 4.1.3.7.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol.
A family of fused-ring hydrocarbons isolated from coal tar that act as intermediates in various chemical reactions and are used in the production of coumarone-indene resins.
A publication issued at stated, more or less regular, intervals.
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.
"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.
Hydrocarbons with at least one triple bond in the linear portion, of the general formula Cn-H2n-2.
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).
Tumors or cancer of the PROSTATE.
A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine.
A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.
Individual's rights to obtain and use information collected or generated by others.
A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.
The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)
The evaluation by experts of the quality and pertinence of research or research proposals of other experts in the same field. Peer review is used by editors in deciding which submissions warrant publication, by granting agencies to determine which proposals should be funded, and by academic institutions in tenure decisions.
An enzyme that catalyzes the conversion of L-CYSTEINE to 3-sulfinoalanine (3-sulfino-L-alanine) in the CYSTEINE metabolism and TAURINE and hypotaurine metabolic pathways.
Method in which repeated blood pressure readings are made while the patient undergoes normal daily activities. It allows quantitative analysis of the high blood pressure load over time, can help distinguish between types of HYPERTENSION, and can assess the effectiveness of antihypertensive therapy.
The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.
Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)
Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed)
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
A synthetic mineralocorticoid with anti-inflammatory activity.
Unstable isotopes of potassium that decay or disintegrate emitting radiation. K atoms with atomic weights 37, 38, 40, and 42-45 are radioactive potassium isotopes.
Measurement of radioactivity in the entire human body.

Aldosterone excretion rate and blood pressure in essential hypertension are related to polymorphic differences in the aldosterone synthase gene CYP11B2. (1/218)

Significant correlation of body sodium and potassium with blood pressure (BP) may suggest a role for aldosterone in essential hypertension. In patients with this disease, the ratio of plasma renin to plasma aldosterone may be lower than in control subjects and plasma aldosterone levels may be more sensitive to angiotensin II (Ang II) infusion. Because essential hypertension is partly genetic, it is possible that altered control of aldosterone synthase gene expression or translation may be responsible. We compared the frequency of 2 linked polymorphisms, one in the steroidogenic factor-1 (SF-1) binding site and the other an intronic conversion (IC), in groups of hypertensive and normotensive subjects. In a larger population, the relationship of aldosterone excretion rate to these polymorphisms was also evaluated. In 138 hypertensive subjects, there was a highly significant excess of TT homozygosity (SF-1) over CC homozygosity compared with a group of individually matched normotensive control subjects. The T allele was significantly more frequent than the C allele in the hypertensive group compared with the control group. Similarly, there was a highly significant relative excess of the conversion allele over the "wild-type" allele and of conversion homozygosity over wild-type homozygosity in the hypertensive group compared with the control group. In 486 subjects sampled from the North Glasgow Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population, SF-1 and IC genotypes were compared with tetrahydroaldosterone excretion rate. Subjects with the SF-1 genotypes TT or TC had significantly higher excretion rates than those with the CC genotype. The T allele was associated with higher excretion rates than the C allele. However, no significant differences were found in excretion rate between subjects of different IC genotype. Urinary aldosterone excretion rate may be a useful intermediate phenotype linking these genotypes to raised BP. However, no causal relationship has yet been established, and it is possible that the polymorphisms may be in linkage with other causative mutations.  (+info)

Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure. (2/218)

BACKGROUND: Cardiac growth and function may be modulated in part by trophic effects of neurohormones. Specifically, aldosterone has been shown to stimulate the growth of cardiac myocytes and the accumulation of cardiac extracellular matrix proteins. Moreover, a variant of the aldosterone synthase gene (a cytosine/thymidine exchange at position -344 in the transcriptional regulatory region) has been associated with enlargement and disturbed filling of the left ventricle (LV) in a small sample of young white adults. The aim of the present study was to reinvestigate the implications of aldosterone synthase -344C/T allele status for serum aldosterone levels, blood pressure, and LV structure and function in large population-based samples. METHODS AND RESULTS: Individuals who participated in the echocardiographic substudy of the third MONICA (MONitoring trends and determinants in CArdiovascular disease) survey (n=1445) or in the second follow-up of the first MONICA survey (n=562) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for aldosterone synthase -344C/T allele status. In both surveys, the distribution of sex, age, arterial blood pressure, and body mass index was homogeneous in the aldosterone synthase genotype groups. Echocardiographic LV wall thicknesses, dimensions, and mass indexes were not significantly associated with a specific aldosterone synthase genotype. Likewise, no association was detectable with echocardiographic measures of LV systolic or diastolic function. Data were consistent in both samples and not materially different in subgroups defined by age, sex, or intake of antihypertensive medication. Finally, no significant association was observed for aldosterone synthase allele status and serum aldosterone levels in the group of 562 individuals. CONCLUSIONS: The data are not in favor of a significant contribution of the C/T exchange at position -344 in the aldosterone synthase transcriptional regulatory region to the variability of serum aldosterone levels, blood pressure, or cardiac size or function as found in 2 white population-based samples.  (+info)

Changes in the glomerulosa cell phenotype during adrenal regeneration in rats. (3/218)

In situ hybridization was used to examine cellular differentiation during rat adrenal regeneration, defining zona glomerulosa [cytochrome P-450 aldosterone synthase (P-450aldo) mRNA positive], zona fasciculata [cytochrome P-450 11beta-hydroxylase (P-45011beta) mRNA positive], or zona intermedia [negative for both but 3beta-hydroxysteroid dehydrogenase (3beta-HSD) mRNA positive]. After unilateral adrenal enucleation with contralateral adrenalectomy (ULE/ULA), the expression of all mRNA was reduced at 2 days. From 5 to 10 days, P-45011beta and 3beta-HSD mRNA increased while P-450aldo remained low; at 20 days, all mRNA were increased. From 2 to 10 days, cells adjacent to the capsule showed intermedia cell differentiation; by 20 days, the subcapsular glomerulosa cells reappeared. This suggests that after enucleation the glomerulosa dedifferentiates to zona intermedia. The experiment was repeated in rats where the postenucleation ACTH rise was prevented. Rats underwent ULE with sham ULA (ULE/SULA) or ULE/SULA with ACTH treatment. Adrenals from ULE/SULA rats expressed increased P-450aldo mRNA at 10 days and reduced P-45011beta mRNA and adrenal weight at 30 days. ACTH treatment reversed the pattern toward that seen in ULE/ULA. These findings show that the enucleation-induced dedifferentitation of the glomerulosa cell may result in part from elevated plasma ACTH and that prevention of dedifferentiation may result in impaired regeneration.  (+info)

Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. (4/218)

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.  (+info)

Modulation of aldosterone biosynthesis by adrenodoxin mutants with different electron transport efficiencies. (5/218)

Aldosterone biosynthesis is highly regulated on different levels by hormones, potassium, lipid composition of the membrane and the molecular structure of its gene. Here, the influence of the electron transport efficiency from adrenodoxin (Adx) to CYP11B1 on the activities of bovine CYP11B1 has been investigated using a liposomal reconstitution system with truncated mutants of Adx. It could be clearly demonstrated that Adx mutants Adx 4-114 and Adx 4-108, possessing enhanced electron transfer abilities, produce increases in corticosterone and aldosterone biosynthesis. Based on the Vmax values of corticosterone and aldosterone formation, Adx 4-108 and Adx 4-114 enhance corticosterone synthesis 1.3-fold and aldosterone formation threefold and twofold, respectively. The production of 18-hydroxycorticosterone was changed only slightly in these Adx mutants. The effect of Adx 1-108 on the product patterns of bovine CYP11B1, human CYP11B1 and human CYP11B2 was confirmed in COS-1 cells by cotransfection of CYP11B- and Adx-containing expression vectors. It could be shown that Adx 1-108 enhances the formation of aldosterone by bovine CYP11B1 and by human CYP11B2, and stimulates the production of corticosterone by bovine CYP11B1 and human CYP11B1 and CYP11B2 also.  (+info)

Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction. (6/218)

BACKGROUND: The -344C allele of a 2-allele (C or T) polymorphism in the promoter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sensitivity, known risk factors for morbidity and mortality associated with myocardial infarction (MI). We hypothesized that this polymorphism was a risk factor for MI. METHODS AND RESULTS: We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic, middle-aged men. There was a nonsignificant trend of increasing risk of MI with number of copies of the -344C allele. However, this allele was associated in a gene dosage-dependent manner with markedly increased MI risk conferred by classic risk factors. Whereas smoking conferred a relative risk of MI of 2.50 (P=0.0001) compared with nonsmokers in the entire study population, the relative risk increased to 4.67 in -344CC homozygous smokers (relative to nonsmokers with the same genotype, P=0.003) and decreased to 1.09 in -344TT homozygotes relative to nonsmokers with this genotype. Similar joint effects were noted with genotype and decreased HDL cholesterol level as combined risk factors. CONCLUSIONS: Smoking and dyslipidemia are more potent risk factors for nonfatal MI in males who have the -344C allele of CYP11B2.  (+info)

Baroreflex sensitivity and variants of the renin angiotensin system genes. (7/218)

OBJECTIVES: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND: Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS: Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS: In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS: Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.  (+info)

Ontogeny of angiotensin II type 1 receptor and cytochrome P450(c11) in the sheep adrenal gland. (8/218)

In the present study we investigated the ontogeny of the expression of the type 1 angiotensin receptor (AT(1)R mRNA) and the zonal localization of AT(1)R immunoreactivity (AT(1)R-ir) and cytochrome P450(c11) (CYP11B-ir) in the sheep adrenal gland. In the adult sheep and in the fetus from as early as 90 days gestation, intense AT(1)R-ir was observed predominantly in the zona glomerulosa and to a lesser extent in the zona fasciculata, and it was not detectable in the adrenal medulla. AT(1)R mRNA decreased 4-fold between 105 days and 120 days, whereas AT(1)R mRNA levels remained relatively constant between 120 days and the newborn period. In contrast, both in the adult sheep and in the fetal sheep from as early as 90 days gestation, intense CYP11B-ir was consistently detected throughout the adrenal cortex and in steroidogenic cells that surround the central adrenal vein. In conclusion, we speculate that the presence of AT(1)R in the zona fasciculata, and the higher levels of expression of AT(1)R at around 100 days gestation, may suggest that suppression of CYP17 is mediated via AT(1)R at this time. The abundant expression of AT(1)R-ir and CYP11B-ir in the zona glomerulosa of the fetal sheep adrenal gland would also suggest that lack of angiotensin II stimulation of aldosterone secretion is not due to an absence of AT(1)R or CYP11B in the zona glomerulosa.  (+info)

TY - JOUR. T1 - Haplotypes of aldosterone synthase (CYP11B2) gene in the general population of Japan. T2 - The Ohasama study. AU - Matsubara, M.. AU - Omori, F.. AU - Fujita, S.. AU - Metoki, H.. AU - Kikuya, M.. AU - Fujiwara, T.. AU - Araki, T.. AU - Imai, Y.. N1 - Funding Information: We are grateful to Mrs. Mika Mikami and Miss Yukiko Sato for technical assistance. This work was supported by Research Grants for Scientific Research (12877163, 13470085, 13671095 and 10470102) from the Ministry of Science and Education, and by Health Science Research Grant for Health Service (H10-025) from the Ministry of Health and Welfare.. PY - 2001. Y1 - 2001. N2 - Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone synthase (CYP11B2) has been one of major targets for molecular analyses in association with hypertension. To date, four polymorphic variants of CYP11B2, -344T/C at promoter region, a gene conversion in intron 2, 2713A/G ...
This is the first report of the effects of pharmacologic inhibition of aldosterone synthase in healthy human subjects. Results obtained with the ASI LCI699 indicate that the hormonal and renal effects of blocking the aldosterone pathway in healthy animals translate to humans. In healthy volunteers, once-daily oral dosing with LCI699 0.5 mg selectively reduced plasma and urinary aldosterone, which was associated with natriuresis and an increase in PRA. LCI699 prolonged survival in a rat disease model induced by ectopic overexpression of human renin and angiotensinogen, and was more effective than the MRA eplerenone in preventing cardiac and renal damage. These results support the therapeutic potential of inhibiting aldosterone synthase in diseases characterized by excessive aldosterone production.. Characterization of LCI699 was performed using in vitro assays and in vivo models in the rat and monkey. LCI699 showed distinct differences between species; it was at least 200-fold less potent in ...
We found that aldosterone production inhibition by FAD286 or ADX protected rats from Ang II-induced inflammatory and fibrotic organ damage. The present data also demonstrated that the main source of cardiac aldosterone in the dTGR model is the adrenal gland. These results show the first description of protection via aldosterone synthase inhibition in vivo. We found previously that MR blockade protects against Ang II-induced organ damage. The MR antagonists spironolactone and eplerenone also reduced mortality and ameliorated renal and cardiac damage in dTGR rats.9,10 Rocha et al15 showed that MR blockade prevents Ang II/salt-induced vascular inflammation in the rat heart. One explanation for this effect might be the interaction between the Ang II receptor and MR. Xiao et al16 demonstrated the aldosterone-potentiated, Ang II-induced proliferation of vascular smooth muscle cells. We showed that aldosterone potentiated Ang II-induced extracellular signal-regulated kinase-1/2 ...
BACKGROUND: Aldosterone is an important cardiovascular hormone; 15% of hypertensive subjects have alteration in aldosterone regulation, defined by a raised ratio of aldosterone to renin (ARR). Studies of the aldosterone synthase gene (CYP11B2) have focused on a single nucleotide polymorphism in the 5promoter region (-344 C/T). In normotensive subjects, the T allele associates with raised levels of the 11-deoxysteroids, deoxycorticosterone and 11-deoxycortisol which are substrates for 11beta-hydroxylase, encoded by the adjacent and homologous gene, CYP11B1. We have speculated that this altered 11beta-hydroxylase efficiency leads to increased ACTH drive to the adrenal gland to maintain cortisol production and reported herein the association between the -344 C/T single nucleotide polymorphism (SNP) and adrenal steroid production in subjects with essential hypertension. METHODS: The CYP11B2-344 C/T polymorphism was genotyped and urinary excretion of adrenal steroid metabolites was measured (by GCMS) in 511
The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase). Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions). But aldosterone synthase is also able to perform a 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and reticularis. Note: aldosterone synthase is absent in other sections of the adrenal gland. ...
Aldosterone Synthase: A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of molecular oxygen and NADPH-specific flavoprotein. This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE.
This study was conducted to assess the relationship between aldosterone synthase CYP1A1 MspI gene polymorphism and prostate cancer risk using meta-analysis.The search was conducted in PubMed and China Biological Medicine Database disc on October 1, 2015, and eligible reports were recruited and synthesized using meta-analysis method.
TY - JOUR. T1 - Expression of cytochromes P450aldo and P45011β in rat adrenal gland during late gestational and neonatal stages. AU - Mitani, Fumiko. AU - Mukai, Kuniaki. AU - Ogawa, Takayoshi. AU - Miyamoto, Hirokuni. AU - Ishimura, Yuzuru. PY - 1997/1. Y1 - 1997/1. N2 - The development of the rat adrenal gland during late gestational and neonatal stages was studied by following the expression of aldosterone synthase cytochrome P450 (P450aldo) and glucocorticoid-synthesizing cytochrome P450 (P45011β). Cells expressing P450aldo, a functional marker for the mineralocorticoid-synthesizing zona glomerulosa, were not detected until day 20 of fetal age, i.e., 2 days before birth, although the zona glomerulosa cells were histologically recognizable at the 18th day of gestation. The intensity of P450aldo staining thereafter became stronger with age in the outer portion of the cortex. Cells expressing P45011β, a marker for the glucocorticoid-producing zona fasciculata, were present in the fetal ...
A novel haplotype of low-frequency variants in the aldosterone synthase gene among northern Han Chinese with essential hypertension. ...
Development of new anti-aldosterone agents focusing on the diverse components of aldosterone production and action is now taking place. Nonsteroidal mineralοcorticoid receptor antagonists are safe and effective therapeutic solutions with finerenone being the most well-studied agent with promising clinical data extending its efficacy in diabetes mellitus, chronic kidney disease and heart failure. Aldosterone synthase inhibitors impact the hormonal balance but there are still limitations regarding the duration of action and adverse effect of the glycolcorticoid axis.. ...
Introduction. Essential hypertension (EH) is a multifactorial disease triggered by several genetic and multiple environmental factors in conjunct. Epidemiological studies have suggested that genetic variants, including those of the genes for angiotensinogen (AGT)1, renin (REN)2, angiotensin-converting enzyme (ACE)3, angiotensin II receptor type 1 (AGTR1)4,5, and aldosterone synthase (CYP11B2)6 increase the risk for EH. However, the influence of polymorphic forms of these genes has shown conflicting results in different populations7,8. This scenario might be reflecting the variable impact of the genetic background of populations and the interaction of environmental factors, which, in turn, might be modulating this molecular background. Recent literature data have shown that unfavorable genotype/allele alone might indicate a minor or nonsignificant association with EH. However, the co-occurrence of different unfavorable genotypes and clinical risk factors can increase the risk of hypertension. ...
Genetic factors account for 30% to 50% of interindividual variability in BP.55,56 Hypertension is most likely a polygenetic disorder with each of the genes contributing modestly to BP. It is possible that menopause might provide the environmental trigger for the expression of certain genetic susceptibilities. Polymorphisms affecting a number of pathways involved in hypertension have been studied. While this is not an exhaustive review of the literature on genetics and hypertension, a few pertinent studies are reviewed.. Sex-specific determinants of genetic susceptibility that are distinct from sex hormone-mediated attenuation of sex-common determinants have been found.57 Several investigators have reported sex specific associations between human hypertension and polymorphisms of components of the RAS,58,59 aldosterone synthase,60 and NO synthase,61 although not in all populations studied.62 A study evaluating the relationship between the extremes of BP with 35 loci that have physiological roles ...
Referenzen: 1. Bezzina, C. R., A. O. Verkerk, A. Busjahn, A. Jeron, J. Erdmann, T. T. Koopmann, Z. A. Bhuiyan, R. Wilders, M. M. Mannens, H. L. Tan, F. C. Luft, H. Schunkert, and A. A. Wilde. 2003. A common polymorphism in KCNH2 (HERG) hastens cardiac repolarization. Cardiovasc.Res. 59:27-36. 2. Broeckel, U., C. Hengstenberg, B. Mayer, S. Holmer, L. J. Martin, A. G. Comuzzie, J. Blangero, P. Nurnberg, A. Reis, G. A. Riegger, H. J. Jacob, and H. Schunkert. 2002. A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat.Genet. 30:210-214. 3. Hengstenberg, C., S. R. Holmer, B. Mayer, H. Lowel, S. Engel, H. W. Hense, G. A. Riegger, and H. Schunkert. 2000. Evaluation of the aldosterone synthase (CYP11B2) gene polymorphism in patients with myocardial infarction. Hypertension 35:704-709. 4. Holmer, S. R., C. Hengstenberg, H. G. Kraft, B. Mayer, M. Poll, S. Kurzinger, M. Fischer, H. Lowel, G. Klein, G. A. Riegger, and H. Schunkert. 2003. Association of polymorphisms of ...
Referenzen: 1. Bezzina, C. R., A. O. Verkerk, A. Busjahn, A. Jeron, J. Erdmann, T. T. Koopmann, Z. A. Bhuiyan, R. Wilders, M. M. Mannens, H. L. Tan, F. C. Luft, H. Schunkert, and A. A. Wilde. 2003. A common polymorphism in KCNH2 (HERG) hastens cardiac repolarization. Cardiovasc.Res. 59:27-36. 2. Broeckel, U., C. Hengstenberg, B. Mayer, S. Holmer, L. J. Martin, A. G. Comuzzie, J. Blangero, P. Nurnberg, A. Reis, G. A. Riegger, H. J. Jacob, and H. Schunkert. 2002. A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat.Genet. 30:210-214. 3. Hengstenberg, C., S. R. Holmer, B. Mayer, H. Lowel, S. Engel, H. W. Hense, G. A. Riegger, and H. Schunkert. 2000. Evaluation of the aldosterone synthase (CYP11B2) gene polymorphism in patients with myocardial infarction. Hypertension 35:704-709. 4. Holmer, S. R., C. Hengstenberg, H. G. Kraft, B. Mayer, M. Poll, S. Kurzinger, M. Fischer, H. Lowel, G. Klein, G. A. Riegger, and H. Schunkert. 2003. Association of polymorphisms of ...
Current Research: Genes do not act in isolation in a cell. Instead, each gene is found in a complex network with many interacting partners. My lab is broadly focused on understanding evolution in metabolic pathways. We have two systems that we are currently using to address how biochemical pathways change. 1) Corticosteroids are a class of important steroid hormones that regulate stress response (cortisol) and salt balance (aldosterone) in tetrapods. In most mammals, a single enzyme (CYP11B) is responsible for making these hormones. Whether CYP11B preferentially produces aldosterone or cortisol is determined by allosterically regulation by another enzyme, CYP11A1. My lab studies the interaction of CYP11B and CYP11A across the mammalian tree to determine the genetic and biochemical mechanisms of allosteric regulation of the corticosteroid pathway in mammals. Students will be offered opportunities in molecular biology, cell culture techniques, proteomics, and bioinformatics.. 2) Hybridization is ...
The effects of retinoids on adrenal aldosterone synthase gene (CYP11B2) expression and aldosterone secretion are still unknown. We therefore examined the effects of nuclear retinoid X receptor (RXR) pan-agonist PA024 on CYP11B2 expression, aldosterone secretion and blood pressure, to elucidate its potential as a novel anti-hypertensive drug. We demonstrated that PA024 significantly suppressed angiotensin II (Ang II)-induced CYP11B2 mRNA expression, promoter activity and aldosterone secretion in human adrenocortical H295R cells. Human CYP11B2 promoter functional analyses using its deletion and point mutants indicated that the suppression of CYP11B2 promoter activity by PA024 was in the region from -1521 (full length) to -106 including the NBRE-1 and the Ad5 elements, and the Ad5 element may be mainly involved in the PA024-mediated suppression. PA024 also significantly suppressed the Ang II-induced mRNA expression of transcription factors NURR1 and NGFIB that bind to and activate the Ad5 element. ...
Circulating aldosterone levels are increased in human pregnancy. Inadequately low aldosterone levels as present in preeclampsia, a life-threatening disease for both mother and child, are discussed to be involved in its pathogenesis or severity. Moreover, inactivating polymorphisms in the aldosterone synthase gene have been detected in preeclamptic women. Here, we used aldosterone synthase-deficient (AS(-/-)) mice to test whether the absence of aldosterone is sufficient to impair pregnancy or even to cause preeclampsia. AS(-/-) and AS(+/+) females were mated with AS(+/+) and AS(-/-) males, respectively, always generating AS(+/-) offspring. With maternal aldosterone deficiency in AS(-/-) mice, systolic blood pressure was low before and further reduced during pregnancy with no increase in proteinuria. Yet, AS(-/-) had smaller litters due to loss of fetuses as indicated by a high number of necrotic placentas with massive lymphocyte infiltrations at gestational day 18. Surviving fetuses and their ...
The major findings of the present study are as follows: (1) AT1A-KO mice with MI had cardiac hypertrophy, cardiac dysfunction, and collagen gene expression, along with increased cardiac expression of the CYP11B2 gene and elevated cardiac aldosterone levels. (2) Spironolactone administration inhibited LV remodeling and resulted in almost normalized LV geometry, as well as reversing altered cardiac gene expressions (ANP, BNP, type I and type III collagens) in AT1A-KO MI mice. These results suggest that aldosterone is produced via an Ang II-independent mechanism in hearts with MI and that it promotes cardiac hypertrophy, fibrosis, and subsequent heart failure after MI.. Several regulators are known to stimulate aldosterone synthesis in the adrenal cortex, including Ang II, corticotropin, and plasma concentrations of Na+ and/or K+. Among these, Ang II is the primary physiological regulator because it is well known that blockade of the renin-angiotensin system by ACE inhibitors or Ang II receptor ...
TY - JOUR. T1 - The establishment of a novel high-throughput screening system using RNA-guided genome editing to identify chemicals that suppress aldosterone synthase expression. AU - Ito, Ryo. AU - Morita, Masanobu. AU - Nakano, Taichi. AU - Sato, Ikuko. AU - Yokoyama, Atsushi. AU - Sugawara, Akira. N1 - Funding Information: This work was supported by JSPS KAKENHI Grant Numbers JP26893012 (RI), JP16K19550 (RI), 19K22793 (AS), 20H04099 (AS), and the Platform Project for Supporting Drug Discovery and Life Science Research from Japan Agency for Medical Research and Development (AMED) . PY - 2021/1/1. Y1 - 2021/1/1. N2 - Aldosterone is synthesized in the adrenal by the aldosterone synthase CYP11B2. Although the control of CYP11B2 expression is important to maintain the mineral homeostasis, its overexpression induced by the depolarization-induced calcium (Ca2+) signaling activation has been reported to increase the synthesis of aldosterone in primary aldosteronism (PA). The drug against PA focused ...
TY - JOUR. T1 - VLDL-activated cell signaling pathways that stimulate adrenal cell aldosterone production. AU - Tsai, Ying Ying. AU - Rainey, William E.. AU - Johnson, Maribeth H.. AU - Bollag, Wendy B.. N1 - Funding Information: This project was supported in part by VA Merit Award #I01BX001344 . Dr. Bollag is supported by a VA Research Career Scientist Award . The contents of this article do not represent the views of the Department of Veterans Affairs or the United States Government. PY - 2016/9/15. Y1 - 2016/9/15. N2 - Aldosterone plays an important role in regulating ion and fluid homeostasis and thus blood pressure, and hyperaldosteronism results in hypertension. Hypertension is also observed with obesity, which is associated with additional health risks, including cardiovascular disease. Obese individuals have high serum levels of very low-density lipoprotein (VLDL), which has been shown to stimulate aldosterone production; however, the mechanisms underlying VLDL-induced aldosterone ...
We performed a large, long-term cohort study to evaluate the association of renin-angiotensin-aldosterone system gene polymorphisms and baseline phenotypes to all-cause mortality among individuals with angiographically confirmed coronary atherosclerosis. higher long-term all-cause mortality, actually after correcting for founded cardiovascular risk factors. As a complex, multifactorial disease that is affected by multiple pathophysiologic, genetic, and environmental factors, atherosclerotic cardiovascular disease (CVD) Pdpn is definitely a major health burden worldwide1,2,3. In addition to additional well-recognized risk factors, the renin-angiotensin-aldosterone system (RAAS) has been implicated in the development of atherosclerosis and coronary heart disease4. The RAAS regulates blood pressure, the sodium and water. Continue Reading. ...
The PNU-74654 (PNU) compound is a non-FDAapproved drug which prevents that Tcf from binding to beta-catenin, acting as a Wnt/beta-catenin antagonist. In NCI-H295 cells,PNU-74654 significantly decreases cell proliferation 96 h after treatment, increases early and late apoptosis, decreases nuclear betacatenin accumulation, impairs CTNNB1/beta-catenin expression and increases betacatenin target genes 48 h after treatment. No effects are observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreases cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreases SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impairs corticosterone secretion 24 h after treatment but does not decrease cell viability[2]. ...
GENETIC RISK ASSESSMENT IN HEART FAILURE: IMPACT OF GENETIC VARIATION OF ALDOSTERONE SYNTHASE PROMOTER POLYMORPHISM - The invention provides methods for (a) reducing mortality associated with heart failure; (b) improving oxygen consumption; (c) treating heart failure; (d) treating hypertension; (e) improving the quality of life in a heart failure patient; (f) inhibiting left ventricular remodeling; (g) reducing hospitalizations related to heart failure; (h) improving exercise tolerance; (j) increasing left ventricular ejection fraction; (Ic) decreasing levels of B-type natriuretic protein; (l) treating renovascular diseases; (m) treating end-stage renal diseases; (n) reducing cardiomegaly; (o) treating diseases resulting from oxidative stress; (p) treating endothelial dysfunctions; (q) treating diseases caused by endothelial dysfunctions; or (r) treating cardiovascular diseases; in a patient in need thereof, wherein the patient has a −344 (T/T) polymorphism or a −344 (C/C) polymorphism in an ...
This compound needs to be synthesised to order. Please email [email protected] if you wish to obtain it, or any other compounds listed on this site.. A full list of 25 novel isoindolinones developed at Imperial can be downloaded from the Files tab above.. JoC code: 4ad. Formula: C17H17NO2. Novel isoindolinone developed via tandem process involving Pd-catalysed Fujiwara−Moritani−aza-Wacker reactions.. 3-Benzyl-substituted-isodolinones are a family of pharmacores of significant interest in therapeutic use. Molecules from this family have previously been patented by pharamceutical companies for use as glycine transporter (GlyT1) and aldosterone synthase (CYP11B2 or CYP11B1) inhibitors.. In addition, many natural products known to have anti-tumour properties comprise a similar substructure, including isoindolobenzazepine alkaloids (e.g., lennoxamine, chileamine) and aristolactam ...
This compound needs to be synthesised to order. Please email [email protected] if you wish to obtain it, or any other compounds listed on this site.. A full list of 25 novel isoindolinones developed at Imperial can be downloaded from the Files tab above.. JoC code: 4da. Formula: C16H15NO. Novel isoindolinone developed via tandem process involving Pd-catalysed Fujiwara−Moritani−aza-Wacker reactions.. 3-Benzyl-substituted-isodolinones are a family of pharmacores of significant interest in therapeutic use. Molecules from this family have previously been patented by pharamceutical companies for use as glycine transporter (GlyT1) and aldosterone synthase (CYP11B2 or CYP11B1) inhibitors.. In addition, many natural products known to have anti-tumour properties comprise a similar substructure, including isoindolobenzazepine alkaloids (e.g., lennoxamine, chileamine) and aristolactam ...
|strong|Mouse anti aldosterone antibody, clone 1-10.1|/strong| recognizes aldosterone, a mineralocorticocoid hormone essential for sodium and potassium homeostasis. Mouse anti aldosterone antibody, cl…
Aldosterone is a hormone secreted by the adrenal glands outer cortex. Acting on the distal tubules and collecting ducts of the nephron, aldosterone stimulates the kidney to reabsorve sodium and release potassium, increasing blood pressure since sodium makes the body retain fluids. ...
Do not stop taking any medicine before talking to your doctor. Your provider may recommend that you eat no more than 3 grams of salt (sodium) per day for at least 2 weeks before the test. Or, your provider will recommend that you eat your usual amount of salt and also test the amount of sodium in your urine. At other times, the aldosterone blood test is done right before and after you receive a salt solution (saline) through the vein (IV) for 2 hours. Be aware that other factors can affect aldosterone measurements, including: ...
Hello, I just started using progesterone and Ive read that using amounts such as 100-2000 mg actually inhibits aldosterone and Im really scared because
GOAL: To describe the structure, synthesis, transport, metabolism and excretion of steroid hormones and the consequences of their deficiencies ...
Glucocorticoid-remediable Aldosteronism in Villivakkam, Chennai - View Doctors, Book an Appointment Online / Find Address - Jithya
Historicallv, aldosterone was classified as a steroid hormone synthesized from the. I backbone cholesterol molecule in the. I mitochondria of the adrenal zona glomerulosa. Recent research has shown that it is produced in many extra-adrenal sites, including cardiovascular tissue. Since the adrenals contain only 1 to 2 pg aldosterone but secrete some 70 to 250 ,ig daily, yielding plasma levels of 5 to 100 pg/mL, it follows that their function is rapid aldosterone synthesis rather than storage. Over 85% of aldosterone is metabolized on first pass through the liver. Thus, its rate of degradation is dependent on hepatic blood flow and its extraction by parenchymal cells, each of which may be impaired in congestive heart failure (CHF).. The main stimuli to aldosterone synthesis by the zona glomerulosa cells are:. Angiotensin-II, the most potent stimulus, acts via AT-II type 1 (ATj) receptors; it also promotes growth of the zona glomerulosa.. Adrenocorticotrophic hormone (ACTH), a stress hormone: the ...
The outermost layer, the zona glomerulosa is the main site for the production of aldosterone, a mineralocorticoid. The synthesis and secretion of aldosterone are mainly regulated by the renin-angiotensin-aldosterone system. The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2).[5][6] Aldosterone is largely responsible for the long-term regulation of blood pressure.[7] Aldosterones effects are on the distal convoluted tubule and collecting duct of the kidney where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct).[7] Sodium retention is also a response of the distal colon, and sweat glands to aldosterone receptor stimulation. Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca2+ channels, isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane ...
The regulation of aldosterone synthesis by the adrenal zona glomerulosa (ZG) cell involves a complex interaction between a wide variety of endogenous stimulatory and inhibitory factors. Angiotensin II (AII), adrenocorticotropic hormone, and potassium ion are the primary secretagogues stimulating aldosterone synthesis (Quinn and Williams, 1988). Atrial natriuretic peptide and decreasing oxygen concentration have been identified as inhibitory factors (Campbell et al., 1985; Raff et al., 1989). Recent investigations in a number of laboratories have indicated the inhibitory effects of NO on the synthesis of various steroid hormones (Adams et al., 1992; Natarajan et al., 1997; Cymeryng et al., 1998). The mechanism of NO inhibition of aldosterone synthesis involves a direct interaction with the cytochrome P450 enzymes required for the multistep conversion of cholesterol into aldosterone (Hanke et al., 1998). The inhibitory effects of NO and the ability of nitric oxide to bind to the cytochrome P450 ...
Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the
Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the
The improvement of conventional imaging techniques has led to an increased detection rate of different adrenal tumors. Since those tumors can belong to a variety of entities the therapeutic consequences also show considerable variation. In order to definitely determine the type of tumor, invasive procedures like CT guided biopsies are often required, which could be avoided by a tumor specific imaging method. The presently available scintigraphic procedures are either time consuming and lead to high radiation exposure or are technically demanding. The steroidogenic enzymes CYP11B1 (11ß-hydroxylase)and CYP11B2 (aldosterone synthase)are expressed exclusively in the adrenal cortex and therefore represent suitable targets for a specific imaging technique. In our project we evaluate 123I-Iodometomidate which binds to both CYP11B enzymes as radiotracer for adrenal scintigraphy ...
Anyone else has high aldosterone? I have symptoms of low aldosterone but I got blood tests and its very high… twice of what the upper limit is… I have no idea why I have this, my blood pressure is normal
Selyatitskaya, V.G.; Mertvetsov, N.P.; Shulga, V.A.; Salganik, R.I.; Kolpakov, M.G., 1985: A study of [3H]aldosterone binding by nuclear and cytoplasmic receptors of the rat kidney with different content of aldosterone in the organism
This test measures the amount of aldosterone in your blood or urine. Aldosterone is a hormone that the adrenal glands make. The level changes throughout the day. Aldosteron ...
Salimetrics has developed and validated an enzyme immunoassay for the measurement of the steroid hormone aldosterone in saliva. This assay is exclusively available via Salimetrics salivary testing.... (PRWeb October 04, 2012). Read the full story at http://www.prweb.com/releases/salivary_aldosterone/salimetrics/prweb9970342.htm ...
Assessment of the Effect of 24-Hour Aldosterone Administration on Protein Abundance in Fluorescence-Sorted Mouse Distal Renal Tubules by Mass Spectrometry ...
Draw upright specimen after the patient is made to sit up for 30 min. Ship refrigerated or frozen. Overnight fasting is preferred ...
The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (AngII). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). In order to characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules (zona reticularis/fasciculata [ZFR]; corticosterone production) were separately dispersed and studied in vitro. Plasma renin activity and angiotensin II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells whereas corticosterone production was not different between WT and KO ZFR cells. As
Tetrahydrodeoxycortisol (THS) is a mineralocorticoid, the main urinary metabolite of 11-deoxycortisol. THS excretion is significantly associated with tetrahydroaldosterone excretion, total androgen excretion, and cortisol metabolites. Aldosterone synthesis is highly heritable and is affected by genotype at CYP11B1. Variation in the region of chromosome 8 including the genes steroid 11-beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) influences mineralocorticoid and glucocorticoid metabolism; differences in 11-hydroxylation efficiency can have downstream effects on mineralocorticoid synthesis. Such effects may be of relevance to the development of low-renin essential hypertension. Genotype differences in CYP11B1 explains approximately 5% of the variance in urinary THS excretion in the population. Excretion of THS is heritable (19.4%) and the T-allele of the -344 C/T polymorphism of CYP11B2 is more strongly associated with higher THS levels than the C-allele. (PMID: 16984984 , ...
Essential hypertension is seen as a contemporary public health challenge not only because of its high prevalence and variable treatment response but also because it represents a major risk factor for cardiovascular disease. Both genetic and environmental factors contribute to the regulation of blood pressure, thus making the study of hypertension difficult and complex. Over recent years, with the advent of new molecular technologies, there has been an increasing interest in its genetic component. Alterations in the rate and pattern of adrenal steroid biosynthesis can contribute to blood pressure changes and its heritable component. In humans, mutations in the genes encoding aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1), responsible for the final stages of aldosterone and cortisol production respectively, lead to rare monogenic disorders. Both, glucocorticoid remediable aldosteronism and 11β-hydroxylase deficiency are associated with mineralocorticoid hypertension. More subtle ...
The comparison of ZG versus ZF transcriptomes has revealed several unsuspected genes many-fold upregulated in human ZG. NEFM was the fourth most upregulated gene in ZG.21 Moreover, its expression was ≈4-fold higher in ZG-like versus ZF-like APAs.22 Our previous functional studies of 2 of the ZG-specific genes, LGR5 and DACH1, showed that they inhibit aldosterone secretion and proliferation. This surprising finding, together with their absence from upregulated genes in rodent ZG26 and patchiness of aldosterone synthase in human adrenal, was interpreted as an adaptive mechanism to high-salt intake in Western diet.20,21. NEFM encodes one of the subunits forming the neurofilament, the type IV intermediate filament of mature neurons, one of the most abundant proteins in the nervous system. Neurofilament subunits perform extracytoskeletal roles in the neuronal synapses as receptor-interacting proteins. For instance, NEFL interacts directly with one of the subunits of the N-methyl-d-aspartate ...
In cirrhosis, the development of ascites and the response to diuretics are determined by the RAAS (renin-angiotensin-aldosterone system) and renal sodium handling system. We hypothesized that SNPs (single nucleotide polymorphisms) affecting candidate genes in the RAAS and renal sodium handling pathway may influence initial diuretic responsiveness and affect clinical outcome in non-azotaemic cirrhotic patients with moderate ascites. We prospectively recruited 176 patients and 245 controls and determined their genetic polymorphisms for 24 SNPs of ten genes involved in the RAAS and renal sodium handling pathway. In cirrhotic patients with moderate ascites, multivariate analysis showed that diuretic unresponsiveness was predicted by a high basal plasma aldosterone level, by a high aldosterone/renin ratio and by specific risk genotypes of ACE (gene encoding angiotensin-converting enzyme), CYP11B2 (gene encoding aldosterone synthase) and ADDA (gene encoding α-adducin). This association between ...
It is 10 years since Davis and his associates have shown that decapitation of hypophysectomized dogs does not alter aldosterone secretion nor prevent a marked increase in aldosterone output in response to hemorrhage. Since then it has been popularly assumed that the reninangiotensin system is the primary regulator of aldosterone secretion. This issue is not yet settled satisfactorily, however. Whereas in man and experimental animals aldosterone secretion continues in the complete absence of the pituitary glands, many investigators have found that hypophysectomy or spontaneous hyperpituitarism results in an impaired aldosterone secretion under basal conditions or under various physiological stimuli. ...
Local resource for aldosterone therapy in Waterloo. Includes detailed information on local businesses that provide access to hormone replacement, chronic aldosterone therapy, aldosterone replacement therapy, HRT therapy, and natural hormone therapy, as well as advice and content on bioidentical hormones.
Local resource for aldosterone therapy in Topeka. Includes detailed information on local businesses that provide access to hormone replacement, chronic aldosterone therapy, aldosterone replacement therapy, HRT therapy, and natural hormone therapy, as well as advice and content on bioidentical hormones.
But sympathetic activity was not increased in the females. That begged the question: What was driving their hypertension? What we observed is that their aldosterone level was sky high, says Belin de Chantemele. While aldosterone also has a positive role in regulating blood pressure, high levels of the steroid hormone are associated with many things that are bad for the cardiovascular system like inflammation and blood vessel stiffness and scarring.. They took a step back and examined the enzyme producing aldosterone, CYP11B2, and found it was also very high in the females. As they began to put the pieces together, they realized that it was leptin that was a direct regulator of the increased aldosterone production by the adrenal gland in the female mice. Since both genders of these mice were hypersensitive to leptin, they were hypertensive but not fat. So they decided to also look at the connection in obese mice, which clearly make more leptin. In the face of high leptin levels, and as with ...
|strong|Sheep anti Aldosterone antibody|/strong| recognizes aldosterone, a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adre…
Aldosteronism is a syndrome caused by excessive and inappropriate aldosterone production and is the most common form of endocrine hypertension. The Endocrine Society suggests a three-tiered approach that includes screening, confirmation of diagnosis, and determination of the specific subtype of primary aldosteronism (PA).
Its also called a serum aldosterone test. ALD is a hormone made by the adrenal glands. The adrenal glands are found on top of your kidneys and are responsible for producing several important hormones
Secreted by the adrenal cortex, aldosterone acts on the distal convoluted tube and causes reabsorption of sodium, potassium excretion ...
The Doctors Laboratory website uses cookies to improve your experience. By continuing to use this site, you are agreeing to our use of cookies.To find out more information, please visit our Cookie Policy page.. ...
Aldosterone synthase (18-hydroxylase; CYP11B2). Prevents the conversion of corticosterone into aldosterone. As such, AG is an ...
CYP11B1 (11β-hydroxylase) is expressed at high levels and is regulated by ACTH, while CYP11B2 (aldosterone synthase) is usually ... Hampf M, Dao NT, Hoan NT, Bernhardt R (September 2001). "Unequal crossing-over between aldosterone synthase and 11beta- ... September 1992). "Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase ... "Structural insights into aldosterone synthase substrate specificity and targeted inhibition". Molecular Endocrinology. 27 (2): ...
... and to a lesser extent via aldosterone synthase (CYP11B2) into 11β-hydroxyprogesterone. In addition, progesterone can be ... "Structural Insights into Aldosterone Synthase Substrate Specificity and Targeted Inhibition". Molecular Endocrinology ( ... Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a ... Progesterone in turn is the precursor of the mineralocorticoid aldosterone, and after conversion to 17α-hydroxyprogesterone, of ...
... serves as an intermediate in the synthesis of aldosterone by the enzyme aldosterone synthase in the ... 18-Hydroxycortisol Aldosterone synthase Reddish MJ, Guengerich FP (August 2019). "Human cytochrome P450 11B2 produces ... aldosterone by a processive mechanism due to the lactol form of the intermediate 18-hydroxycorticosterone". The Journal of ...
... by the aldosterone synthase enzyme (CYP11B2). Along with its epimer 11α-hydroxyprogesterone (11α-OHP), 11β-OHP has been ... and aldosterone synthase (CYP11B2) that convert progesterone to 11β-OHP.[verification needed] That's why in 21-hydroxylase ... "Structural insights into aldosterone synthase substrate specificity and targeted inhibition". Molecular Endocrinology. 27 (2): ... In the normal route to aldosterone and cortisol, progesterone and 17α-hydroxyprogesterone are first hydroxylated at position 21 ...
2002). "Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase". Endocrinology. 143 (9): 3651- ... Komeima K, Hayashi Y, Naito Y, Watanabe Y (2000). "Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin- ... 1999). "Regulation of neuronal nitric-oxide synthase by calmodulin kinases". J. Biol. Chem. 274 (29): 20597-602. doi:10.1074/ ... "Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/ ...
... is converted to aldosterone by aldosterone synthase, found only in the mitochondria of glomerulosa cells. ... Steroidogenesis Deoxycorticosterone Aldosterone 11-Deoxycortisol 11-Deoxycorticosterone Cortisol R.A. Hill; H.L.J. Makin; D.N. ... Corticosterone is the precursor molecule to the mineralocorticoid aldosterone, one of the major homeostatic modulators of ... potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone. ...
The CYP11B2 gene provides instructions for making another enzyme called aldosterone synthase, which helps produce aldosterone. ... too much aldosterone synthase is produced. This overproduction causes the adrenal glands to make excess aldosterone, which ... produce too much of the hormone aldosterone. Excess aldosterone causes the kidneys to retain more salt than normal, which in ... The abnormal ion flow results in the activation of biochemical processes (pathways) that lead to increased aldosterone ...
... by the action of the enzyme aldosterone synthase. Aldosterone plays an important role in the long-term regulation of blood ... "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant". Biochem ... In the kidneys, aldosterone acts on the distal convoluted tubules and the collecting ducts by increasing the reabsorption of ... Aldosterone is responsible for the reabsorption of about 2% of filtered glomerular filtrate. Sodium retention is also a ...
The enzyme aldosterone synthase (also known as CYP11B2) acts in this location The expression of neuron-specific proteins in the ... Zhou, M.Y.; Gomez-Sanchez, C.E. (1993). "Cloning and Expression of a Rat Cytochrome P-450 11β-Hydroxylase/Aldosterone Synthase ... the 2 major regulators of aldosterone production. Aldosterone regulates the body's concentration of electrolytes, primarily ... Ye, P.; Mariniello, B.; Mantero, F.; Shibata, H.; Rainey, W. E (2007). "G-protein-coupled receptors in aldosterone-producing ...
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... The last part is mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). ... and aldosterone (C 21H 28O 5). (Note that cortisone and aldosterone are isomers.) The main corticosteroids produced by the ... Mineralocorticoids such as aldosterone are primarily involved in the regulation of electrolyte and water balance by modulating ...
Cortisol 18-Hydroxycorticosterone Aldosterone synthase Steroid 11β-hydroxylase Lenders J, Williams T, Reincke M, Gomez-Sanchez ... Increased synthesis is also found in patients with aldosterone-producing adenomas. ACTH stimulation test increases urinary ...
"Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, ... molecular dynamics simulation studies also indicate that ethyl caffeate is a potential inhibitor of the aldosterone synthase ( ... CYP11B2), a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure ...
It specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β- ...
Aldosterone synthase (CYP11B2) inhibitors such as metyrapone, mitotane, and osilodrostat prevent the production of the potent ... Farnesyl pyrophosphate synthase (FPPS) inhibitors prevent the conversion of isopentenyl pyrophosphate (IPP) into farnesyl ... Jürg Müller (6 December 2012). Regulation of Aldosterone Biosynthesis. Springer Science & Business Media. pp. 39-. ISBN 978-3- ... and aldosterone from the less potent corticosteroids 11-deoxycorticosterone and 11-deoxycortisol and are used in the diagnosis ...
... and Aldosterone synthase (CYP11B2). CYP11 can be divided into A to E five subfamilies, and CYP11A are the ohonologues to CYP11C ...
Hyperaldosteronism Pseudohyperaldosteronism Glucocorticoid-remediable aldosteronism Aldosterone and aldosterone synthase Maria ... In serum both aldosterone and renin levels are low. This disorder presents similarly to hyperaldosteronism, leading to feedback ... The inactivating mutation leads to elevated local concentrations of cortisol in the aldosterone sensitive tissues like the ... leading to aldosterone-like effects in the kidney. This is what causes the hypokalemia, hypertension, and hypernatremia ...
Aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex. Aldosterone synthase ... The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). ... It selectively stimulates secretion of aldosterone. The secretion of aldosterone has a diurnal rhythm. Control of aldosterone ... ACTH increases the activity of existing aldosterone synthase, resulting in an abnormally high rate of aldosterone synthesis and ...
It may be increased in 17α-hydroxylase (CYP17A1) deficiency, in aldosterone synthase (CYP11B2) deficiency, in primary ... reference data for neonates and infants and its application in aldosterone-synthase deficiency". Journal of Chromatography. B, ...
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... The last part is mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). ... 5) and aldosterone (C. 21H. 28O. 5). (Note that aldosterone and cortisone share the same chemical formula but the structures ... Mineralocorticoids such as aldosterone are primarily involved in the regulation of electrolyte and water balance by modulating ...
... by the action of the enzyme aldosterone synthase.[16][17] Aldosterone plays an important role in the long-term regulation of ... "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant". Biochem ... In the kidneys, aldosterone acts on the distal convoluted tubules and the collecting ducts by increasing the reabsorption of ... Angiotensin II and extracellular potassium are the two main regulators of aldosterone production.[19] The amount of sodium ...
The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2).[5][6] Aldosterone is largely ... The synthesis and secretion of aldosterone are mainly regulated by the renin-angiotensin-aldosterone system. ... is produced in the adrenocortical zona glomerulosa by the action of the enzyme aldosterone synthase (also known as CYP11B2).[5] ... 6] Aldosterone is largely responsible for the long-term regulation of blood pressure.[7] Aldosterone effects on the distal ...
Corticosterone is then converted to aldosterone by aldosterone synthase. Most of the DOC is secreted by the zona fasciculata of ... DOC has about 1/20 of the sodium retaining power of aldosterone, and is said to be as little as one per cent of aldosterone at ... DOC is a precursor molecule for the production of aldosterone. The major pathway for aldosterone production is in the adrenal ... Since DOC has about 1/5 the potassium excreting power of aldosterone, it probably must have aldosterone's help if the serum ...
The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largely ... The synthesis and secretion of aldosterone are mainly regulated by the renin-angiotensin-aldosterone system. ... is produced in the adrenocortical zona glomerulosa by the action of the enzyme aldosterone synthase (also known as CYP11B2). ... "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant". Biochem. ...
... downregulating aldosterone synthase, CYP11B1, and the production of adrenal steroids (i.e. aldosterone and cortisol). The first ...
... aldosterone synthase, CYP11B2), and 3β-hydroxysteroid dehydrogenase (3β-HSD) to a lesser extent. In addition, mitotane has ...
... aldosterone synthase MeSH D12.776.422.220.453.915.099 - aromatase MeSH D12.776.422.220.453.915.200 - cholesterol 7 alpha- ... aldosterone MeSH D12.776.827.275.700.500 - tacrolimus binding protein 1a MeSH D12.776.828.075.350.275 - filgrastim MeSH D12.776 ...
... the Gene mutated will result in an aldosterone synthase that is ACTH-sensitive, which is normally not. GRA appears to be the ... Compare these effects to those seen in Conn's disease, an adrenocortical tumor which causes excess release of aldosterone, that ... Ziaja J, Cholewa K, Mazurek U, Cierpka L (2008). "[Molecular basics of aldosterone and cortisol synthesis in normal adrenals ... DOC has blood-pressure raising effects similar to aldosterone, and abnormally high levels result in hypokalemic hypertension. ...
... aldosterone synthase) - mineralocorticoid synthesis 21-Hydroxylase - corticosteroid synthesis Cytochrome P450 (CYP1, 2, 3) - ...
... effects of spironolactone may also in part be mediated by direct inactivation of 11β-hydroxylase and aldosterone synthase (18- ... Couette B, Marsaud V, Baulieu EE, Richard-Foy H, Rafestin-Oblin ME (1992). "Spironolactone, an aldosterone antagonist, acts as ... 364-. ISBN 978-1-4557-3801-4. Spironolactone is an aldosterone antagonist and a relatively weak antiandrogen that blocks the AR ... Spironolactone inhibits the effects of mineralocorticoids, namely, aldosterone, by displacing them from MR in the cortical ...
Aldosterone synthase. *Frataxin. *Mitochondrial membrane transport protein *Mitochondrial permeability transition pore. * ...
positive regulation of glycogen (starch) synthase activity. Sources:Amigo / QuickGO. Orthologs. Species. Human. Mouse. ...
Dito gumagalaw ang enzyme na aldosterone synthase Mga talasanggunian[baguhin , baguhin ang batayan]. ... Pinangangasiwaan ng aldosterone ang balanse ng konsentrasyon o dami ng mga electrolyte, nangunguna na ang antas ng sodium at ... naglalabas ang mga selula ng zona glomerulosa ng mineralocorticoid na kung tawagin ay aldosterone patungo sa dugo bilang bahagi ...
citrate (Si)-synthase activity. • RNA binding. Cellular component. • mitochondrial matrix. • extracellular exosome. • ... Citrate synthase has three key amino acids in its active site (known as the catalytic triad) which catalyze the conversion of ... Citrate synthase catalyzes the condensation reaction of the two-carbon acetate residue from acetyl coenzyme A and a molecule of ... The enzyme citrate synthase E.C. 2.3.3.1 (previously 4.1.3.7)] exists in nearly all living cells and stands as a pace-making ...
Aldosterone and corticosteroids are also derived from progesterone or its derivatives.. *Pregnenolone can be converted to 17α- ... Pregnenolone can be converted to androstadienol by 16-ene synthase (CYP17A1).. *Pregnenolone can be converted to pregnenolone ...
Angiotensin II - Induces Aldosterone synthesis and release (zona glomerulosa of adrenal cortex in kidney) ...
... downregulating aldosterone synthase, CYP11B1, and the production of adrenal steroids (i.e. aldosterone and cortisol).[29] ...
Specific substrates include testosterone, progesterone, androstenedione, epitestosterone, cortisol, aldosterone, and ... although different from aldosterone. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may ... "Antinatriuretic and kaliuretic activities of the reduced derivatives of aldosterone". Endocrinology. 112 (5): 1852-6. doi: ... Thymidylate synthase. *2.4 PARP. *2.5 Dihydropteroate synthetase. *Farnesyltransferase. *2.6 GABA transaminase. *2.7 ...
Aldosterone synthase. *Frataxin. *Mitochondrial membrane transport protein *Mitochondrial permeability transition pore. * ...
Aldosterone synthase. *Frataxin. *Mitochondrial membrane transport protein *Mitochondrial permeability transition pore. * ...
... is also required for induction of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS). Both are ... including those responsible for the binding of aldosterone, androgen, estrogen, and progesterone. Cancerous cells overexpress a ... "Transient interaction of Hsp90 with early unfolding intermediates of citrate synthase. Implications for heat shock in vivo". J ... M domain of hsp90 serves as a molecular scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide synthase ...
Aldosterone synthase. *Frataxin. *Mitochondrial membrane transport protein *Mitochondrial permeability transition pore. * ...
The enzyme aldosterone synthase (also known as CYP11B2) acts in this location[3][4] The expression of neuron-specific proteins ... Zhou, M.Y.; Gomez-Sanchez, C.E. (1993). "Cloning and Expression of a Rat Cytochrome P-450 11β-Hydroxylase/Aldosterone Synthase ... the 2 major regulators of aldosterone production.[2] Aldosterone regulates the body's concentration of electrolytes, primarily ... Ye, P.; Mariniello, B.; Mantero, F.; Shibata, H.; Rainey, W. E (2007). "G-protein-coupled receptors in aldosterone-producing ...
Drapala A, Sikora M, Ufnal M (September 2014). "Statins, the renin-angiotensin-aldosterone system and hypertension - a tale of ... Thymidylate synthase. *2.4 PARP. *2.5 Dihydropteroate synthetase. *Farnesyltransferase. *2.6 GABA transaminase. *2.7 ... another beneficial effect of statins". Journal of the Renin-Angiotensin-Aldosterone System. 15 (3): 250-58. doi:10.1177/ ...
Aldosterone synthase. *Frataxin. *Mitochondrial membrane transport protein *Mitochondrial permeability transition pore. * ...
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... The last parts are mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone ... Control of aldosterone release from the adrenal cortexEdit. The renin-angiotensin system, showing role of aldosterone between ... Aldosterone is part of the renin-angiotensin-aldosterone system. It has a plasma half-life of under 20 minutes.[6] Drugs that ...
Aldosterone synthase. other. *Glutamate aspartate transporter. *Glycerol-3-phosphate dehydrogenase. *ATP synthase ...
... nitric oxide synthase, and glutathione.[23] ...
Biotin synthase mechanism: An overview. Biochemical Society Transactions, 2005, 33, 820 - 823. B. Rüdiger, B. Tse Sum Bui, V. ... The main areas covered are : steroid biochemistry: inhibition of the biosynthesis of aldosterone (among the various compounds ... Iron-sulfur clusters of biotin synthase in vivo: a Mössbauer study. Biochemistry, 2002, 41, 15000-15006. E. Davioud, A. ... problem to which Andrée Marquet and her team have made a decisive contribution is that of the mechanism of biotin synthase, ...
Aldosterone is synthesized by following the metabolism of progesterone. In the potential case where aldosterone synthase is not ... Deficient aldosterone synthase activity results in impaired biosynthesis of aldosterone while corticosterone in the zona ... Aldosterone synthase converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone ... aldosterone synthase (encoded by CYP11B2 gene) catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that ...
Aldosterone is synthesized by following the metabolism of progesterone. In the potential case where aldosterone synthase is not ... Deficient aldosterone synthase activity results in impaired biosynthesis of aldosterone while corticosterone in the zona ... Aldosterone synthase converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone ... aldosterone synthase (encoded by CYP11B2 gene) catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that ...
Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2). We tested the hypothesis that reducing ... aldosterone after ADX and reduction of aldosterone due to pharmacological intervention with the aldosterone synthase inhibitor ... the key enzyme in the production of aldosterone is the aldosterone synthase or CYP11B2. CYP11B2 was isolated in 1992 by ... 2 The key enzyme in aldosterone production is aldosterone synthase (CYP11B2). CYP11B2 is predominantly expressed in the adrenal ...
... is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE. ... Aldosterone Synthase: A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of ... Aldosterone Synthase (CYP11B2). Subscribe to New Research on Aldosterone Synthase A mitochondrial cytochrome P450 enzyme that ... 06/01/2006 - "Previous studies have shown that the aldosterone synthase promoter polymorphism -344T/C influences aldosterone ...
... potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial ...
in-licenses aldosterone synthase inhibitors from ElexoPharm GmbH, complementing its ongoing program in chronic kidney disease ... target aldosterone synthase (CYP11B2), a cytochrome P450 enzyme involved in the generation of aldosterone. Reducing aldosterone ... Angion Biomedica Exclusively In-licenses Aldosterone Synthase Inhibitors from ElexoPharm GmbH Complementing its Ongoing Program ... ElexoPharm obtained its aldosterone synthase inhibitors from the lab of Professor Rolf Hartmann, a world-renowned expert in ...
Correction to "A Novel Mitochondrial Complex of Aldosterone Synthase, Steroidogenic Acute Regulatory Protein, and Tom22 ... A Novel Mitochondrial Complex of Aldosterone Synthase, Steroidogenic Acute Regulatory Protein, and Tom22 Synthesizes ... A Novel Mitochondrial Complex of Aldosterone Synthase, Steroidogenic Acute Regulatory Protein, and Tom22 Synthesizes ... Aldosterone Synthesis in the Heart. Himangshu S. Bose, Randy M. Whittal, Brendan Marshall, Maheshinie Rajapaksha, Ning Ping ...
Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase or Cytochrome P450Aldo or Cytochrome P450C18 or Steroid 18 Hydroxylase ... Inhibition of aldosterone synthase is used as a medical treatment for hypertension, heart failure, and renal disorders. ... It also reviews key players involved in Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase or Cytochrome P450Aldo or ... The report provides a snapshot of the global therapeutic landscape for Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase ...
Aldosterone Synthase produced in E. coli aa 25-503 with 6His-SUMO, N-terminus tag(s). ... Aldosterone Synthase Protein LS-G56197 is a Recombinant Human CYP11B2 / ... CYP11B2 / Aldosterone Synthase Protein LS-G56197 is a Recombinant Human CYP11B2 / Aldosterone Synthase produced in E. coli aa ... CYP11B2 / Aldosterone Synthase Protein LS-G56197 is a Recombinant Human CYP11B2 / Aldosterone Synthase produced in E. coli aa ...
... resulting in lack of aldosterone. Structure-function studies have identified aldosterone synthase residues specifically ... Human aldosterone synthase and 11[beta]-hydroxylase: studies on the relationship of structure and function and their clinical ... Fisher, Angela (1999) Human aldosterone synthase and 11[beta]-hydroxylase: studies on the relationship of structure and ... This thesis presents new studies on the relationship between structure and function of aldosterone synthase and 11-hydroxylase ...
Since aldosterone is derived from a final conversion of 18-hydroxycorticosterone into aldosterone by aldosterone synthase, we ... aldosterone synthase inhibitor, 62 ± 2). Conclusions: Local production of aldosterone by its processing enzyme aldosterone ... Detection of aldosterone, as well as its processing enzyme aldosterone synthase, CYP11B2 mRNA, and protein in dorsal root ... Detection of aldosterone, as well as its processing enzyme aldosterone synthase, CYP11B2 mRNA, and protein in dorsal root ...
Aldosterone synthase inhibitors in cardiovascular and renal diseases 529 Relation between aldosterone synthase polymorphism and ... SP285ANGIOTENSIN-CONVERTING ENZYME GENE (ACE), ALDOSTERONE SYNTHASE GENE (CYP11B2) AND ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE ( ... An aldosterone synthase gene variant is associated with improvement in left ventricular ejection fraction in dilated ... Angiotensin II-aldosterone interaction in human coronary microarteries involves GPR30, EGFR, and endothelial NO synthase ...
Pharmacodynamic effects of aldosterone synthase inhibition: single-dose phase. Plasma and urinary aldosterone. Single doses of ... Pharmacodynamic effects of aldosterone synthase inhibition: multiple-dose phase. Plasma and urinary aldosterone. Compared with ... Selective inhibition of aldosterone synthase appears to be a promising approach to treat diseases associated with aldosterone ... In the first 12 h after dosing, LCI699 effectively inhibited the activity of aldosterone synthase and plasma aldosterone was ...
The major goal of our study was to define the Ang II-induced mechanisms regulating the expression of aldosterone synthase ( ... Angiotensin II (Ang II) is the major physiological regulator of aldosterone production acting acutely to stimulate aldosterone ... Aldosterone is principally synthesized in the zona glomerulosa of the adrenal by a series of enzymatic reactions leading to the ... represent important mechanisms to increase the adrenal capacity to produce aldosterone. ...
This study was conducted to assess the relationship between aldosterone synthase CYP1A1 MspI gene polymorphism and prostate ... Relationship Between Aldosterone Synthase CYP1A1 MspI Gene Polymorphism and Prostate Cancer Risk. This study was conducted to ... assess the relationship between aldosterone synthase CYP1A1 MspI gene polymorphism and prostate cancer risk using meta-analysis ...
"Induction of citrate synthase by aldosterone in the rat kidney",. abstract = "The possible induction of renal citrate synthase ... Induction of citrate synthase by aldosterone in the rat kidney. The Journal of Membrane Biology. 1978 Mar 1;41(1):41-64. https ... Law, P-Y & Edelman, IS 1978, Induction of citrate synthase by aldosterone in the rat kidney, The Journal of Membrane Biology ... Law, P-Y., & Edelman, I. S. (1978). Induction of citrate synthase by aldosterone in the rat kidney. The Journal of Membrane ...
Aldosterone Synthase Inhibitors. Decreasing aldosterone synthesis at its enzyme step, aldosterone synthase (AS), CYP11B2, is ... Aldosterone synthase inhibitors (ASI) represent the latest therapeutic strategy to decrease aldosterone production [110]. ... J. Ménard, M.-F. Gonzalez, T.-T. Guyene, and A. Bissery, "Investigation of aldosterone-synthase inhibition in rats," Journal of ... W. B. Lea, E. S. Kwak, J. M. Luther et al., "Aldosterone antagonism or synthase inhibition reduces end-organ damage induced by ...
We evaluated the influence of C-344T polymorphism of the aldosterone synthase gene, associated with aldosterone levels and the ... Influence of aldosterone synthase gene C-344T polymorphism on focal segmental glomerulosclerosis.. Bantis C1, Heering PJ, ... Our results indicate that aldosterone synthase gene C-344T polymorphism not only acts as a risk factor for the development of ...
Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension. Journal ... Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in ... Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in ... Conclusion: The T-344C and A6547G, but not the T4986C, variants of the aldosterone synthase gene are associated with HT in ...
... ... Involvement of vascular aldosterone synthase in phosphate-induced osteogenic transformation of vascular smooth muscle cells. ...
Disorders of aldosterone synthesis and action Autoimmune adrenalitis (Addison disease) Aldosterone synthase (CYP11B2). ...
Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone ... "Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone ... Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone ... Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone ...
J Renin Angiotensin Aldosterone Syst. 2016 Mar 23;17(1):1470320316633896. doi: 10.1177/1470320316633896. Print 2016 Jan-Mar. ... Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis.. Xu H1, Wang X2 ... Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis ... Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis ...
Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. Molecular and Cellular ... Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. :: Molecular and ... Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism. / Nishimoto, Koshiro; ... フィンガープリント Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism の研究トピックを掘り下げ ...
Roumen, L.. / A computational study of the substrate conversion and selective inhibition of aldosterone synthase. Eindhoven : ... Roumen, L 2008, A computational study of the substrate conversion and selective inhibition of aldosterone synthase, Doctor in ... Roumen L. A computational study of the substrate conversion and selective inhibition of aldosterone synthase. Eindhoven: ... Roumen, L. (2008). A computational study of the substrate conversion and selective inhibition of aldosterone synthase. ...
The Aldosterone Synthase Inhibitor FAD286 is Suitable for Lowering Aldosterone Levels in ZDF Rats but not in db/db Mice. ... Impact of Aldosterone Synthase Inhibitor FAD286 on Steroid Hormone Profile in Human Adrenocortical Cells. ... Aldosterone Synthase Inhibition Improves Glucose Tolerance in Zucker Diabetic Fatty (ZDF) Rats. ... Selectivity of BI 689648, a Novel, Highly Selective Aldosterone Synthase Inhibitor: Comparison with FAD286 and LCI699 in ...
Ogishima T, Mitani F, Ishimura Y. Isolation of two distinct cytochromes P-45011β with aldosterone synthase activity from bovine ... Ogishima, T, Mitani, F & Ishimura, Y 1989, Isolation of two distinct cytochromes P-45011β with aldosterone synthase activity ... Ogishima, T., Mitani, F., & Ishimura, Y. (1989). Isolation of two distinct cytochromes P-45011β with aldosterone synthase ... Isolation of two distinct cytochromes P-45011β with aldosterone synthase activity from bovine adrenocortical mitochondria. In: ...
Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism.. October 25, 2016 ... Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism.. ... Our group previously purified human and rat aldosterone synthase (CYP11B2 and Cyp11b2, respectively) from their adrenals and ... In adults, the adrenal cortex remodels and subcapsular aldosterone-producing cell clusters (APCCs) replace the continuous ZG ...
Aldosterone synthase deficiency and related disorders. Mol Cell Endocrinol. 2004. 217:81-87. [Medline]. ... Weir MR, Rolfe M. Potassium homeostasis and Renin-Angiotensin-aldosterone system inhibitors. Clin J Am Soc Nephrol. 2010 Mar. 5 ... Mechanisms of impaired potassium handling with dual renin-angiotensin-aldosterone blockade in chronic kidney disease. ...
The CYP11B2 gene provides instructions for making an enzyme called aldosterone synthase (previously known as corticosterone ... Aldosterone synthase helps produce a hormone called aldosterone. Aldosterone helps control blood pressure by maintaining proper ... In the fusion gene, ACTH binding abnormally triggers production of aldosterone synthase. High levels of aldosterone synthase ... The aldosterone synthase enzyme is involved in a series of three chemical reactions that produce aldosterone from other ( ...
In particular, annulated chiral pyrrolidines with alpha stereogenic centers have aldostereone synthase inhibition activity. In ...
  • Aldosterone synthase is encoded on chromosome 8q22 by the CYP11B2 gene. (wikipedia.org)
  • Whereas steroid 11β-hydroxylase (encoded by CYP11B1 gene) only catalyzes hydroxylation at position 11 beta (mainly of 11-deoxycorticosterone and 11-deoxycortisol), aldosterone synthase (encoded by CYP11B2 gene) catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that successively requires hydroxylation at positions 11 beta and 18 and oxidation at position 18. (wikipedia.org)
  • The in-active proteins are caused by the autosomal recessive inheritance of defective CYP11B2 genes in which genetic mutations destroy the enzymatic activity of aldosterone synthase. (wikipedia.org)
  • Aldosterone concentrations depend on the activity of aldosterone synthase (CYP11B2). (ahajournals.org)
  • We tested the hypothesis that reducing aldosterone by inhibiting CYP11B2 or by adrenalectomy (ADX) may ameliorate organ damage. (ahajournals.org)
  • 1,2 The key enzyme in aldosterone production is aldosterone synthase (CYP11B2). (ahajournals.org)
  • 3 Angiotensin (Ang) II is the main stimulus for CYP11B2-related aldosterone synthesis. (ahajournals.org)
  • This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE. (curehunter.com)
  • or =1 C-encoding allele in CYP11B2-encoded aldosterone synthase. (curehunter.com)
  • Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. (nih.gov)
  • UNIONDALE, N.Y.--( BUSINESS WIRE )--Angion Biomedica Corp. announced today that it has signed an exclusive license with ElexoPharm GmbH of Saarbrücken, Germany, for compounds that target aldosterone synthase (CYP11B2), a cytochrome P450 enzyme involved in the generation of aldosterone. (businesswire.com)
  • Dr. Hartmann's team identified novel classes of highly selective aldosterone synthase inhibitors (CYP11B2) that spare the closely related CYP11B1 target. (businesswire.com)
  • The latest report Cytochrome P450 11B2 Mitochondrial Pipeline Review, H2 2017, outlays comprehensive information on the Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase or Cytochrome P450Aldo or Cytochrome P450C18 or Steroid 18 Hydroxylase or CYP11B2 or EC 1.14.15.4 or EC 1.14.15.5 targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action MoA, route of administration RoA and molecule type. (bioportfolio.com)
  • It also reviews key players involved in Cytochrome P450 11B2 Mitochondrial Aldosterone Synthase or Cytochrome P450Aldo or Cytochrome P450C18 or Steroid 18 Hydroxylase or CYP11B2 or EC 1.14.15.4 or EC 1.14.15.5 targeted therapeutics development with respective active and dormant or discontinued projects. (bioportfolio.com)
  • CYP11B2 / Aldosterone Synthase Protein LS-G56197 is a Recombinant Human CYP11B2 / Aldosterone Synthase produced in E. coli aa 25-503 with 6His-SUMO, N-terminus tag(s). (lsbio.com)
  • Analogous mutations in the human CYP11B2 gene in exons 3 and 4 which result in amino acid substitutions, E136D and K251R have been shown to increase aldosterone production. (gla.ac.uk)
  • The major goal of our study was to define the Ang II-induced mechanisms regulating the expression of aldosterone synthase (CYP11B2) in adrenocortical cells. (openrepository.com)
  • These events are followed by increased CYP11B2 expression and, therefore, represent important mechanisms to increase the adrenal capacity to produce aldosterone. (openrepository.com)
  • Since the identification of a chimeric aldosterone synthase which induces mendelian hypertension, polymorphisms in aldosterone synthase (CYP11B2) has been one of major targets for molecular analyses in association with hypertension. (elsevier.com)
  • Association of aldosterone synthase (CYP11B2) -344 T/C polymorphism with diabetic nephropathy: A meta-analysis. (cdc.gov)
  • This meta-analysis aimed to systematically summarize the association between aldosterone synthase (CYP11B2) gene polymorphism and diabetic nephropathy risk. (cdc.gov)
  • Our meta-analysis indicates that aldosterone synthase (CYP11B2) gene polymorphism may contribute to diabetic nephropathy development, especially in Asian group, with the T allele acting as a risk factor. (cdc.gov)
  • Forest plot for the overall analysis for aldosterone synthase CYP11B2 polymorphism and diabetic nephropathy risk for allele comparison (T vs. C). (cdc.gov)
  • Begg's funnel plot for publication bias test of the association between aldosterone synthase CYP11B2 polymorphism and diabetic nephropathy risk. (cdc.gov)
  • Our group previously purified human and rat aldosterone synthase (CYP11B2 and Cyp11b2, respectively) from their adrenals and verified that it is distinct from steroid 11β-hydroxylase (CYP11B1 or Cyp11b1), the cortisol- or corticosterone-synthesizing enzyme. (elsevier.com)
  • Immunohistochemistry for CYP11B2 and CYP11B1 has become an important tool for the diagnosis of and research on adrenocortical pathological conditions and suggests that APCCs may be the origin of aldosterone-producing adenoma. (elsevier.com)
  • The biosynthesis of aldosterone is performed by two cytochrome p450 enzymes, 11B1 and 11B2, denoted as CYP11B1 and CYP11B2, respectively. (tue.nl)
  • From these two family members, only CYP11B2 can perform the final synthesis step that converts 18-hydroxycorticosterone into aldosterone. (tue.nl)
  • The CYP11B2 gene provides instructions for making an enzyme called aldosterone synthase (previously known as corticosterone methyloxidase). (medlineplus.gov)
  • At least 30 CYP11B2 gene mutations that cause corticosterone methyloxidase deficiency (also known as aldosterone synthase deficiency) have been identified. (medlineplus.gov)
  • This change joins (fuses) the section of the CYP11B2 gene that contains the instructions for making aldosterone synthase to a section of a nearby gene called CYP11B1 . (medlineplus.gov)
  • Connell JM, Fraser R, MacKenzie SM, Friel EC, Ingram MC, Holloway CD, Davies E. The impact of polymorphisms in the gene encoding aldosterone synthase (CYP11B2) on steroid synthesis and blood pressure regulation. (medlineplus.gov)
  • To explore the relationship between genetic polymorphisms of C-344T in the promoter region and K173R in the exon 3 of aldosterone synthase gene ( CYP11B2 ) and the incidence of essential hypertension in a northern Chinese Han population . (bvsalud.org)
  • Myocardial aldosterone synthase ( CYP11B2 ) was detected by quantitative real-time PCR . (bvsalud.org)
  • Studies of the aldosterone synthase gene (CYP11B2) have focused on a single nucleotide polymorphism in the 5'promoter region (-344 C/T). In normotensive subjects, the T allele associates with raised levels of the 11-deoxysteroids, deoxycorticosterone and 11-deoxycortisol which are substrates for 11beta-hydroxylase, encoded by the adjacent and homologous gene, CYP11B1. (ox.ac.uk)
  • CAH due to aldosterone synthase (CYP11B2) causes a decrease in aldosterone level without affecting cortisol levels. (medscape.com)
  • Although CYP11B1 and CYP11B2 share 95% homology, the former regulates the final steps in cortisol synthesis, whereas the latter regulates the final steps in aldosterone synthesis. (medscape.com)
  • 1166AC) and aldosterone synthase CYP11B2 (−344CT). (ahajournals.org)
  • Nguyen HH, Hannemann F, Hartmann MF, Malunowicz EM, Wudy SA, Bernhardt R. Five novel mutations in CYP11B2 gene detected in patients with aldosterone synthase deficiency type I: Functional characterization and structural analyses. (medlineplus.gov)
  • In cirrhotic patients with moderate ascites, multivariate analysis showed that diuretic unresponsiveness was predicted by a high basal plasma aldosterone level, by a high aldosterone/renin ratio and by specific risk genotypes of ACE (gene encoding angiotensin-converting enzyme), CYP11B2 (gene encoding aldosterone synthase) and ADDA (gene encoding α-adducin). (clinsci.org)
  • Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity. (annals.org)
  • The levels of Cyp11b2 (aldosterone synthase), but not the other adrenal steroidogenic genes, were decreased in testosterone females. (pubmedcentralcanada.ca)
  • These results suggest that prenatal testosterone exposure downregulates adrenal Cyp11b2 expression, leading to decreased plasma aldosterone levels. (pubmedcentralcanada.ca)
  • Aldosterone synthase gene (CYP11B2) C-344T polymorphism in Caucasians from the Berlin Salt-Sensitivity Trial (BeSST). (semanticscholar.org)
  • Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. (proteopedia.org)
  • The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2 ). (wikipedia.org)
  • The primary mineralocorticoid , aldosterone , is produced in the adrenocortical zona glomerulosa by the action of the enzyme aldosterone synthase (also known as CYP11B2 ). (wikipedia.org)
  • Inhibitors of CYP11B2 (aldosterone synthase) will also be dealt with. (eurekaselect.com)
  • Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure. (physiciansweekly.com)
  • The effects of retinoids on adrenal aldosterone synthase gene (CYP11B2) expression and aldosterone secretion are still unknown. (physiciansweekly.com)
  • We therefore examined the effects of nuclear retinoid X receptor (RXR) pan-agonist PA024 on CYP11B2 expression, aldosterone secretion and blood pressure, to elucidate its potential as a novel anti-hypertensive drug. (physiciansweekly.com)
  • We demonstrated that PA024 significantly suppressed angiotensin II (Ang II)-induced CYP11B2 mRNA expression, promoter activity and aldosterone secretion in human adrenocortical H295R cells. (physiciansweekly.com)
  • The resected tumor histologically separated from the liver was composed of clear cells, immunohistochemically positive for aldesterone synthase (CYP11B2), and subsequently diagnosed as aldosterone-producing adrenal adenoma. (doaj.org)
  • The article presents the data of foreign and national literature on the pathogenetic role of aldosterone (AL), levels of aldosterone synthase (AS) and gene polymorphisms of this enzyme in patients with various forms of arterial hypertension, associated with diseases of the heart and vessels, such as hypertrophic cardiomyopathy, atrial fibrillation, brain pathology etc. (zaslavsky.com.ua)
  • The objective of this study was to assess aldosterone polymorphisms and relationships to plasma aldosterone levels and the development of renal histological lesions in kidney transplant patients . (bvsalud.org)
  • We determined aldosterone synthase (AS) -344 T/C and int 2 W/C gene polymorphisms and plasma aldosterone levels. (bvsalud.org)
  • Evaluation of renin-angiotensin-aldosterone system gene polymorphisms. (semanticscholar.org)
  • We analyzed the association between salt sensitivity in essential hypertension and 8 genetic polymorphisms in 6 genes of the renin-angiotensin aldosterone system. (semanticscholar.org)
  • Objective: To determine the influence of genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) on ECG and two dimensional echocardiographic left ventricular hypertrophy (LVH) in genetically identical patients with HCM. (bmj.com)
  • Moreover, inactivating polymorphisms in the aldosterone synthase gene have been detected in preeclamptic women. (uzh.ch)
  • Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B. (nih.gov)
  • ElexoPharm obtained its aldosterone synthase inhibitors from the lab of Professor Rolf Hartmann, a world-renowned expert in this field. (businesswire.com)
  • The therapeutic potential of targeting adrenal steroid synthesis to inhibit aldosterone production has not been fully explored due to the lack of selective aldosterone synthase inhibitors (ASIs). (biomedcentral.com)
  • Weir MR, Rolfe M. Potassium homeostasis and Renin-Angiotensin-aldosterone system inhibitors. (medscape.com)
  • The patent application relates to new heterocyclic compounds of the general formula (I) in which R, R1, R2, W, X, Y, Z and n have the definitions elucidated in more detail in the description, to a process for preparing them and to the use of these compounds as medicaments, particularly as aldosterone synthase inhibitors. (justia.com)
  • The invention relates to new heterocycles, to processes for preparing the compounds according to the invention, to pharmaceutical products comprising them, and to their use as active pharmaceutical ingredients, in particular as aldosterone synthase inhibitors. (justia.com)
  • Furthermore, it is well-established that inhibitors of the renin-angiotensin-aldosterone system (RAAS) reduce cardiovascular ischemic events (i.e., heart attack and stroke) and mortality ( 3 - 6 ). (diabetesjournals.org)
  • This pathway depicts a simplified representation of the pharmacodynamics (PD) of RAAS-acting drugs including candidate genes for the pharmacogenomics (PGx) of ACE inhibitors, angiotensin receptor blockers (ARBs), renin inhibitor aliskiren and aldosterone receptor antagonists. (wikipathways.org)
  • Relationship Between Aldosterone Synthase CYP1A1 MspI Gene Polymorphism and Prostate Cancer Risk. (onctoday.com)
  • This study was conducted to assess the relationship between aldosterone synthase CYP1A1 MspI gene polymorphism and prostate cancer risk using meta-analysis. (onctoday.com)
  • Influence of aldosterone synthase gene C-344T polymorphism on focal segmental glomerulosclerosis. (cdc.gov)
  • We evaluated the influence of C-344T polymorphism of the aldosterone synthase gene, associated with aldosterone levels and the development of arterial hypertension, on focal segmental glomerulosclerosis (FSGS). (cdc.gov)
  • Our results indicate that aldosterone synthase gene C-344T polymorphism not only acts as a risk factor for the development of FSGS, but also may influence its pathologic appearance and could serve as a marker of disease progression. (cdc.gov)
  • Studies on the relation between aldosterone synthase -344 T/C polymorphism and diabetic nephropathy showed controversial conclusions. (cdc.gov)
  • Aldosterone synthase gene polymorphism as a determinant of atrial fibrillation in patients with heart failure. (medlineplus.gov)
  • Aldosterone synthase gene polymorphism and renal histopathologic changes in kidney transplant patients receiving a calcineurin inhibitor. (bvsalud.org)
  • Associations between aldosterone synthase gene polymorphism and the adrenocortical function in males. (semanticscholar.org)
  • 597 Association between the renin-angiotensin-aldosterone system gene polymorphism and heart failure of ischemic aetiology. (ebscohost.com)
  • An abstract of the study "Association Between the Renin-Angiotensin-Aldosterone System Gene Polymorphism and Heart Failure of Ischemic Aetiology," by M. Mendonca and colleagues, is presented. (ebscohost.com)
  • Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. (wikipedia.org)
  • Aldosterone synthase converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone: 11-deoxycorticosterone Corticosterone 18-hydroxycorticosterone Aldosterone In human metabolism the biosynthesis of aldosterone largely depends on the metabolism of cholesterol. (wikipedia.org)
  • Lack of metabolically active aldosterone synthase leads to corticosterone methyl oxidase deficiency type I and II. (wikipedia.org)
  • Deficient aldosterone synthase activity results in impaired biosynthesis of aldosterone while corticosterone in the zona glomerulosa is excessively produced in both corticosterone methyl oxidase deficiency type I and II. (wikipedia.org)
  • The aldosterone synthase enzyme is involved in a series of three chemical reactions that produce aldosterone from other (precursor) molecules: the conversion of 11-deoxycorticosterone to corticosterone, the conversion of corticosterone to 18-hydroxycorticosterone, and the conversion of 18-hydroxycorticosterone to aldosterone. (medlineplus.gov)
  • Corticosterone methyloxidase deficiency, also known as aldosterone synthase deficiency, is a disorder characterized by excessive amounts of sodium released in the urine (salt wasting), along with insufficient release of potassium in the urine, usually beginning in the first few weeks of life. (medlineplus.gov)
  • Aldosterone and corticosterone share the first part of their biosynthetic pathways. (wikipedia.org)
  • The last parts are mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). (wikipedia.org)
  • Some common natural hormones are corticosterone (C 21 H 30 O 4 ), cortisone (C 21 H 28 O 5 , 17-hydroxy-11-dehydrocorticosterone), and aldosterone . (newworldencyclopedia.org)
  • Aldosterone and corticosterone share the first part of their biosynthetic pathway. (newworldencyclopedia.org)
  • The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). (newworldencyclopedia.org)
  • Corticosterone is then converted to aldosterone by aldosterone synthase. (hmdb.ca)
  • Serum corticosterone, which is like aldosterone released from the adrenal cortex, was more than doubled in SPRED2 KOs, too. (uni-wuerzburg.de)
  • Similar to corticosterone, the production of aldosterone is at least in part under control of pituitary ACTH, which is further regulated by upstream hypothalamic CRH release. (uni-wuerzburg.de)
  • It is the sole enzyme capable of synthesizing aldosterone in humans and plays an important role in electrolyte balance and blood pressure. (wikipedia.org)
  • Aldosterone synthase is the enzyme that has steroid 18-hydroxylase activity as well as steroid 11 beta-hydroxylase activity. (wikipedia.org)
  • enzyme involved in the biosynthesis of the mineralocorticoid aldosterone. (bioportfolio.com)
  • A heme‐thiolate enzyme that converts 11‐deoxycorticosterone to aldosterone, by successive hydroxylations at the 11 β and 18 positions. (oup.com)
  • Aldosterone augmented methionine incorporation into renal citrate synthase by 55% but had no effect on incorporation into the hepatic enzyme. (umn.edu)
  • This gene provides instructions for making an enzyme called aldosterone synthase. (medlineplus.gov)
  • The aldosterone synthase enzyme is found in the adrenal glands, which are located on top of the kidneys. (medlineplus.gov)
  • [6] Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives, like lisinopril , which lowers blood pressure by blocking the angiotensin-converting enzyme (ACE), leading to lower aldosterone secretion. (wikipedia.org)
  • there is complete deficiency of enzyme activity that leads to very low levels of cortisol and aldosterone. (merckmanuals.com)
  • In the simple virilizing form, cortisol synthesis is impaired, leading to increased androgen activity, but there is sufficient enzyme activity to maintain normal, or only slightly decreased, aldosterone production. (merckmanuals.com)
  • The enzyme 17α-hydroxylase-C17,20-lyase (P45017, CYP 17, androgen synthase), a cytochrome P450 monooxygenase, is the key enzyme for androgen biosynthesis. (eurekaselect.com)
  • PA024 also suppressed the Ang II-induced mRNA expression of StAR, HSD3β2 and CYP21A2, a steroidogenic enzyme group involved in aldosterone biosynthesis. (physiciansweekly.com)
  • Inhibition of aldosterone synthase is currently being investigated as a medical treatment for hypertension, heart failure, and renal disorders. (wikipedia.org)
  • Reducing aldosterone levels may be an effective approach to treating chronic kidney disease, heart failure, hypertension and fibrosis. (businesswire.com)
  • In essential hypertension adrenal steroids have been implicated as a contributing factor in some cases and it is possible that mutations in aldosterone synthase and 11-hydroxylase may be responsible in part for abnormalities in steroid production. (gla.ac.uk)
  • High levels of aldosterone synthase result in excessive aldosterone production, which leads to the hypertension associated with familial hyperaldosteronism type I. (medlineplus.gov)
  • The correlation between excretion of aldosterone and cortisol metabolites and suggests that, in TT subjects, ACTH exerts an important common regulatory influence on adrenal corticosteroid production in subjects with hypertension. (ox.ac.uk)
  • Atrial natriuretic peptide and aldosterone synthase gene in essential hypertension: a case-control study. (semanticscholar.org)
  • I lead a translational research group investigating the role of the mineralocorticoid aldosterone in cardiovascular disease, in particular hypertension and stroke. (gla.ac.uk)
  • In the overweight and obese individual, as well as in persons with hypertension, systemic and vascular insulin resistance often occur in concert with elevations in plasma aldosterone. (diabetesjournals.org)
  • Structural analysis and evaluation of the aldosterone synthase gene in hypertension. (semanticscholar.org)
  • Polymorphysms of the aldosterone synthase gene in essential hypertension. (ad-astra.ro)
  • It is used for the treatment of potassium depletion and hypertension, and is the specific therapy for hypertension due to overactivity of the ENaC (Liddle syndrome and several additional genetic causes of the Liddle phenotype - low renin and low aldosterone). (scielo.org.za)
  • A 31-year-old man with Williams syndrome (WS) was referred to our hospital because of a 9-year history of hypertension, hypokalemia, and high plasma aldosterone concentration to renin activity ratio. (doaj.org)
  • These mutations lead to insufficient production of aldosterone, which impairs the kidneys' ability to reabsorb salt (sodium chloride or NaCl) into the blood and release potassium in the urine. (medlineplus.gov)
  • In the fusion gene, ACTH binding abnormally triggers production of aldosterone synthase. (medlineplus.gov)
  • the ACTH stimulation test , which is sometimes used to stimulate the production of aldosterone along with cortisol to determine whether primary or secondary adrenal insufficiency is present. (wikipedia.org)
  • The outermost layer, the zona glomerulosa is the main site for the production of aldosterone , a mineralocorticoid . (wikipedia.org)
  • Although sustained production of aldosterone requires persistent calcium entry through low-voltage activated Ca 2+ channels , isolated zona glomerulosa cells are considered nonexcitable, with recorded membrane voltages that are too hyperpolarized to permit Ca 2+ channels entry. (wikipedia.org)
  • Adrenocorticotropic hormone is assumed to play a role in the regulation of aldosterone synthase likely through stimulating the synthesis of 11-deoxycorticosterone which is the initial substrate of the enzymatic action in aldosterone synthase. (wikipedia.org)
  • 15% of hypertensive subjects have alteration in aldosterone regulation, defined by a raised ratio of aldosterone to renin (ARR). (ox.ac.uk)
  • The presence of cortisol in fetal adrenals suggests that adrenal regulation of circulating fetal ACTH remains a factor in development of congenital adrenal hyperplasia during the second trimester, while a relative lack of aldosterone explains the salt-wasting disorders frequently seen in extreme pre-term neonates. (springer.com)
  • We tested the hypothesis that prenatal testosterone exposure induces dysregulation of the renin-angiotensin-aldosterone system, which is known to play an important role in water and electrolyte balance and blood pressure regulation. (pubmedcentralcanada.ca)
  • The zona glomerulosa is the outer zone and only secretes aldosterone, a mineralcorticoid responsible for salt, water, and potassium regulation in the body. (newworldencyclopedia.org)
  • Our research focuses on the regulation of aldosterone production by the adrenal gland and its action via the mineralocorticoid receptor and we have active collaborations with groups in Europe and the USA. (gla.ac.uk)
  • The regulation of aldosterone synthase expression. (wikipathways.org)
  • Mineralocorticoids such as aldosterone are primarily involved in the regulation of electrolyte and water balance by modulating ion transport in the epithelial cell s of the renal tubules of the kidney . (wikipedia.org)
  • [5] [6] Aldosterone is largely responsible for the long-term regulation of blood pressure . (wikipedia.org)
  • Deactivation of enzymatic activity reduces aldosterone concentrations in plasma and tissues which decreases mineralocorticoid receptor-dependent and independent effects in cardiac vascular and renal target organs. (wikipedia.org)
  • 9,10 The aim of the present study was to define the effect of FAD286 and the role of circulating or locally produced aldosterone in the pathogenesis of Ang II-induced renal and cardiac damage. (ahajournals.org)
  • The effects of LCI699 and eplerenone on cardiac and renal sequelae of aldosterone excess were investigated in a double-transgenic rat (dTG rat) model overexpressing human renin and angiotensinogen. (biomedcentral.com)
  • In the dTG rat model, LCI699 dose-dependently blocked increases in aldosterone, prevented development of cardiac and renal functional abnormalities independent of blood pressure changes, and prolonged survival. (biomedcentral.com)
  • These results provide new insights into the cardiac and renal effects of inhibiting aldosterone synthase in experimental models and translation of the hormonal effects to humans. (biomedcentral.com)
  • The possible induction of renal citrate synthase (E.C. 4.1.3.7), by aldosterone was evaluated in the adrenalectomized rat. (umn.edu)
  • Three hours after administration of aldosterone (0.8 μg/100 g body wt), renal cortical and medullary citrate synthase activity was significantly increased as reported previously by Kinne and Kirsten (Kinne, R., Kirsten, R. 1968. (umn.edu)
  • Three hours after the injection, renal citrate synthase was isolated by ATP-sepharose column chromatography and immuno-precipitation with the specific antiserum. (umn.edu)
  • The rennin-angiotensin-aldosterone system (RAAS), one of the most important hormonal systems, oversees the functions of cardiovascular, renal, and adrenal glands by regulating blood pressure, fluid volume, and sodium and potassium balance [ 1 ]. (hindawi.com)
  • Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. (bvsalud.org)
  • In cirrhosis, the development of ascites and the response to diuretics are determined by the RAAS (renin-angiotensin-aldosterone system) and renal sodium handling system. (clinsci.org)
  • [4] When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and renal disease . (wikipedia.org)
  • Renal tubular acidosis (RTA) is acidosis and electrolyte disturbances due to impaired renal hydrogen ion excretion (type 1), impaired bicarbonate resorption (type 2), or abnormal aldosterone production or response (type 4). (merckmanuals.com)
  • Aldosterone may act on the central nervous system via the posterior pituitary gland to release vasopressin (ADH) which serves to conserve water by direct actions on renal tubular resorption. (wikidoc.org)
  • Aldosterone synthase inhibition provides the potential to attenuate both the mineralocorticoid receptor-dependent and independent actions of aldosterone. (biomedcentral.com)
  • Hormonal effects of orally administered LCI699 were examined in rat and monkey in vivo models of adrenocorticotropic hormone (ACTH) and angiotensin-II-stimulated aldosterone release, and were compared with the mineralocorticoid receptor antagonist eplerenone in a randomized, placebo-controlled study conducted in 99 healthy human subjects. (biomedcentral.com)
  • These experimental data together with growing clinical evidence for the benefits of blocking the actions of aldosterone with mineralocorticoid receptor antagonists (MRAs) in the treatment of heart failure [ 3 ]-[ 5 ] provide the rationale for new therapeutic approaches to inhibit aldosterone production. (biomedcentral.com)
  • For this purpose, in 36 12-week old, salt-restricted, nephrectomized Sprague-Dawley rats, we studied the effects of the Ang II AT 1 -subtype receptor antagonist losartan and of the Ang II AT 2 -subtype receptor antagonist PD123319 on renin mRNA and activity, aldosterone synthase mRNA, and AT 1a -, AT 1b -, and AT 2 -subtype receptor expression in the adrenal cortex. (ahajournals.org)
  • Conversely, renin-angiotensin-aldosterone system and mineralocorticoid receptor (MR) antagonism reduces cardiovascular risk in these patient populations. (diabetesjournals.org)
  • Recent and accumulating evidence in this area has implicated excessive Ser phosphorylation and proteosomal degradation of the docking protein, insulin receptor substrate, and enhanced signaling through hybrid insulin/IGF-1 receptor as important mechanisms underlying aldosterone-mediated interruption of downstream vascular insulin signaling. (diabetesjournals.org)
  • The aldosterone/MR receptor complex binds on the DNA to specific hormone response element , which leads to gene specific transcription . (wikidoc.org)
  • Preoperative aldosterone receptor blockade and outcomes of cardiac surgery in patients with chronic kidney disease. (amedeo.com)
  • [7] Sodium retention is also a response of the distal colon, and sweat glands to aldosterone receptor stimulation. (wikipedia.org)
  • Furthermore, we investigated how much local cardiac aldosterone originates from the adrenal gland. (ahajournals.org)
  • Deoxycorticosterone (DOC) is a C-21 (21 carbon atoms) steroid hormones synthesized in the zona fasciculata (ZF) and zona glomerulosa (ZG) of the adrenal gland and is a precursor for the synthesis of cortisol and aldosterone (see the image below). (medscape.com)
  • Deoxycorticosterone (DOC) is a C-21 (21 carbon atoms) steroid hormone synthesized in zona fasciculata (ZF) and zona glomerulosa (ZG) of the adrenal gland and is a precursor for the synthesis of cortisol and aldosterone (see the image below). (medscape.com)
  • The human fetal adrenal gland produces cortisol but very low levels of Δ 4 androgens and no detectable aldosterone throughout the second trimester. (springer.com)
  • Aldosterone , the main mineralocorticoid hormone, is a steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland . (wikipedia.org)
  • Note: aldosterone synthase is absent in other sections of the adrenal gland . (wikipedia.org)
  • Aldosterone is a steroid hormone ( mineralocorticoid family) produced by the outer-section ( zona glomerulosa ) of the adrenal cortex in the adrenal gland to regulate sodium and potassium balance in the blood . (wikidoc.org)
  • If decreased blood pressure is detected, the adrenal gland is stimulated by these stretch receptors to release aldosterone, which increases sodium reabsorption from the urine, sweat and the gut. (wikidoc.org)
  • 11-Deoxycorticosterone (also called desoxycortone, 21-hydroxyprogesterone, DOC, or simply deoxycorticosterone) is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid activity and acts as a precursor to aldosterone. (hmdb.ca)
  • Situated along the perimeter of the adrenal gland , the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids , such as aldosterone and cortisol , respectively. (wikipedia.org)
  • However, aldosterone synthase expression in the adrenal gland was substantially augmented. (uni-wuerzburg.de)
  • This included haplotype analysis and measurement of plasma aldosterone levels. (edu.au)
  • There was also no relationship with plasma aldosterone levels. (bvsalud.org)
  • Accordingly, plasma aldosterone levels were lower in testosterone females. (pubmedcentralcanada.ca)
  • Indeed, basic and clinical studies have demonstrated that elevated plasma aldosterone levels predict the development of insulin resistance and that aldosterone directly interferes with insulin signaling in vascular tissues. (diabetesjournals.org)
  • Furthermore, elevated plasma aldosterone levels are associated with increased heart attack and stroke risk. (diabetesjournals.org)
  • The relationships between the inhibition of steroid 11β-hydroxylase, aldosterone synthase and aromatase enzymes and the electronic structure of a group of coumarin derivatives was analyzed. (derpharmachemica.com)
  • Mineralocorticoids are a class of steroid hormones characterized by their similarity to aldosterone and their influence on salt and water balance. (newworldencyclopedia.org)
  • Ulick, S., Wang, J.Z. and Morton, D.H. (1992) The biochemical phenotypes of two inborn errors in the biosynthesis of aldosterone. (scirp.org)
  • Selective inhibition of aldosterone synthase appears to be a promising approach to treat diseases associated with aldosterone excess. (biomedcentral.com)
  • Angiotensin II (Ang II) is the major physiological regulator of aldosterone production acting acutely to stimulate aldosterone biosynthesis and chronically to increase the capacity of the adrenals to produce aldosterone. (openrepository.com)
  • In the potential case where aldosterone synthase is not metabolically active the body accumulates 11-deoxycorticosterone. (wikipedia.org)
  • In contrast to eplerenone, LCI699 increased the aldosterone precursor 11-deoxycorticosterone and urinary potassium excretion. (biomedcentral.com)
  • Both forms of cytochrome P-450 11β were capable of catalyzing aldosterone synthesis as well as the 11β- and 18-hydroxylation of 11-deoxycorticosterone. (elsevier.com)
  • The deficiency completely or partially blocks conversion of 17-hydroxyprogesterone to 11-deoxycortisol, a precursor of cortisol, and conversion of progesterone to deoxycorticosterone, a precursor of aldosterone. (merckmanuals.com)
  • Deoxycorticosterone stimulates the collecting tubules in the kidney to continue to excrete potassium in much the same way that aldosterone does. (hmdb.ca)
  • Deoxycorticosterone has about 1/20 of the sodium retaining power of aldosterone and about 1/5 the potassium excreting power of aldosterone ( Wikipedia ). (hmdb.ca)
  • White, P.C. (2004) Aldosterone synthase deficiency and related disorders. (scirp.org)
  • Aldosterone synthase deficiency type I: hormonal and genetic analyses of two cases. (medlineplus.gov)
  • 21-Hydroxylase (CYP21A2) deficiency causes defective conversion of adrenal precursors to cortisol and, in some cases, to aldosterone, sometimes resulting in severe hyponatremia and hyperkalemia . (merckmanuals.com)
  • Aldosterone deficiency can lead to salt wasting, hyponatremia , and hyperkalemia ( 1 , 2 ). (merckmanuals.com)
  • With maternal aldosterone deficiency in AS(-/-) mice, systolic blood pressure was low before and further reduced during pregnancy with no increase in proteinuria. (uzh.ch)
  • Our results demonstrate that aldosterone deficiency has profound adverse effects on placental function. (uzh.ch)
  • In this animal model, aldosterone deficiency did not cause preeclampsia. (uzh.ch)
  • A cross talk between renin-angiotensin-aldosterone system (RAAS) and sympathetic nerve system could play some roles in the cardiovascular system. (ahajournals.org)
  • The renin-angiotensin-aldosterone system (RAAS) is central to the control of blood pressure and the target of several types of anti-hypertensive drugs. (wikipathways.org)
  • Ogishima, T , Mitani, F & Ishimura, Y 1989, ' Isolation of two distinct cytochromes P-450 11β with aldosterone synthase activity from bovine adrenocortical mitochondria ', Journal of biochemistry , vol. 105, no. 4, pp. 497-499. (elsevier.com)
  • Spironolactone treatment abolished endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS) phosphorylation (Ser 1177 ) in arteries from db/db mice, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. (frontiersin.org)
  • Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney . (newworldencyclopedia.org)
  • Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which is nearly equal to the entire sodium content in human blood under normal GFR ( glomerular filtration rate ). (wikidoc.org)
  • [7] Aldosterone 's effects are on the distal convoluted tubule and collecting duct of the kidney where it causes increased reabsorption of sodium and increased excretion of both potassium (by principal cells) and hydrogen ions (by intercalated cells of the collecting duct). (wikipedia.org)
  • Aldosterone increases the permeability of the apical (luminal) membrane of the kidney's collecting ducts to potassium and sodium and activates their basolateral Na+/K+ pumps, stimulating ATP hydrolysis, reabsorbing sodium (Na+) ions and water into the blood, and excreting potassium (K+) ions into the urine. (hmdb.ca)
  • In the search for an alternative therapeutic application, we have studied a novel treatment involving the selective inhibition of aldosterone biosynthesis. (tue.nl)
  • J Renin Angiotensin Aldosterone Syst. (cdc.gov)
  • J Renin Angiotensin Aldosterone Syst;15(3): 301-6, 2014 Sep. (bvsalud.org)
  • At birth the adrenals are essential for neonate salt retention through secretion of aldosterone, while adequate glucocorticoids are required to prevent adrenal insufficiency. (springer.com)
  • Cholesterol is metabolized in what is known as the early pathway of aldosterone synthesis and is hydroxylated becoming (20R,22R)-dihydroxycholesterol which is then metabolized as a direct precursor to pregnenolone. (wikipedia.org)
  • Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. (bvsalud.org)
  • Chun et al 6 found that spironolactone induced integrin-β protein expression in cultured rat cardiomyocytes and A6 cells, whereas aldosterone diminished integrin-β protein expression in both of these cell types. (ahajournals.org)
  • Female rats (6 mo old) prenatally exposed to testosterone were examined for adrenal expression of steroidogenic genes, telemetric blood pressure, blood volume and Na + and K + levels, plasma aldosterone, angiotensin II and vasopressin levels, and vascular responses to angiotensin II and arg 8 -vasopressin. (pubmedcentralcanada.ca)
  • Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. (proteopedia.org)
  • COX-2-derived PGE2 triggers hyperplastic renin expression and hyperreninemia in aldosterone synthase-deficient mice. (abcam.com)
  • on the other hand, in combination with elevated aldosterone synthase expression, this upregulated HPA hormone release explains hyperaldosteronism and the associated salt and water imbalances. (uni-wuerzburg.de)
  • Antagonists of aldosterone have provided better treatment options, however, side-effects are still observed. (tue.nl)
  • Prevention or restoration of these changes via blockade of aldosterone action in the vascular wall with MR antagonists (i.e., spironolactone, eplerenone) may therefore account for the clinical benefit of these compounds in obese and diabetic patients with cardiovascular disease. (diabetesjournals.org)
  • Aldosterone is the primary of several endogenous members of the class of mineralocorticoids in human. (wikidoc.org)
  • Mechanisms of impaired potassium handling with dual renin-angiotensin-aldosterone blockade in chronic kidney disease. (medscape.com)
  • The increased potassium level works to regulate aldosterone synthesis by depolarizing the cells in the zona glomerulosa , which opens the voltage-dependent calcium channels . (wikipedia.org)
  • Serum potassium concentrations are the most potent stimulator of aldosterone secretion. (wikipedia.org)
  • An alternative approach to inhibiting the effects of aldosterone is blocking the renin-angiotensin system (RAS), which decreases aldosterone production indirectly. (biomedcentral.com)
  • An abstract of the study "Cardiovascular Effects and Angiotensin System Adaptation in Experimental Heart Failure After Aldosterone Synthase Inhibition," by V. Mellin and colleagues is presented. (ebscohost.com)
  • Since the publication of 2 clinical trials, RALES (Randomized Aldactone Evaluation Study) and EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study), the role of aldosterone in cardiovascular remodeling has generated considerable attention. (ahajournals.org)
  • Mutations have been identified which destroy aldosterone synthase 18-hydroxylase activity or 18-oxidase activity or both, resulting in lack of aldosterone. (gla.ac.uk)
  • However, spironolactone alone had a protective effect against reperfusion injury in the absence of aldosterone or cortisol infusion suggestive of a direct, inverse agonist action. (ahajournals.org)
  • Here, we used aldosterone synthase-deficient (AS(-/-)) mice to test whether the absence of aldosterone is sufficient to impair pregnancy or even to cause preeclampsia. (uzh.ch)
  • Recent emerging evidence suggests that extra-adrenal synthesis of aldosterone occurs ( e.g. , within the failing heart and in certain brain areas). (asahq.org)
  • Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution? (wikipathways.org)
  • Epidemiological studies demonstrate a clear correlation between elevated aldosterone levels and increased rates of cardiovascular disease (CVD) in patients with and without primary hyperaldosteronism ( 1 , 2 ). (diabetesjournals.org)
  • Circulating and cardiac aldosterone levels were reduced in FAD286 or losartan-treated dTGR. (ahajournals.org)
  • ADX combined with dexamethasone and salt treatment decreased circulating and cardiac aldosterone to barely detectable levels. (ahajournals.org)
  • Both FAD286 and ADX reduced circulating and cardiac aldosterone levels. (ahajournals.org)
  • The present results show that aldosterone produced in the adrenals is the main source of cardiac aldosterone. (ahajournals.org)
  • In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). (bvsalud.org)
  • Studies by Rebsamen et al 4 have shown that aldosterone applied to cultured cardiac myocytes can provoke increases in inflammatory cytokines and that this action could be blocked by spironolactone but not RU486. (ahajournals.org)
  • The main humoral, metabolic, cellular, immune-inflammatory and profibrogenic effects of aldosterone are considered. (zaslavsky.com.ua)
  • The synthesis and secretion of aldosterone are mainly regulated by the renin-angiotensin-aldosterone system . (wikipedia.org)
  • The secretion of aldosterone is also stimulated by ACTH. (wikipedia.org)
  • The main corticosteroids produced by the adrenal cortex are cortisol and aldosterone. (wikipedia.org)
  • Aldosterone synthase is a protein which is only expressed in the zona glomerulosa of the adrenal cortex and is primarily regulated by the renin-angiotensin system. (wikipedia.org)
  • Aldosterone is principally synthesized in the zona glomerulosa of the adrenal by a series of enzymatic reactions leading to the conversion of cholesterol to aldosterone. (openrepository.com)
  • Aldosterone is synthesized by following the metabolism of progesterone. (wikipedia.org)
  • Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay . (bvsalud.org)
  • The authors found in an ex vivo model of regional myocardial ischemia (30 minutes) followed by reperfusion with Krebs-Henseleit buffer (2.5 hours) that aldosterone or cortisol infusion could increase infarct size. (ahajournals.org)
  • Since salt and water balance is primarily under hormonal control of aldosterone and AVP, we analyzed both hormone levels. (uni-wuerzburg.de)
  • Aldosterone stimulates H + secretion by intercalated cells in the collecting duct, regulating plasma bicarbonate (HCO 3 − ) levels and its acid/base balance. (wikidoc.org)
  • however, aldosterone levels can be elevated even though Ang II production is inhibited or its action is blocked. (ahajournals.org)
  • Aldosterone helps control blood pressure by maintaining proper salt and fluid levels in the body. (medlineplus.gov)
  • Serum aldosterone and renin levels were low ( Box 2 ). (mja.com.au)
  • Circulating aldosterone levels are increased in human pregnancy. (uzh.ch)
  • Inadequately low aldosterone levels as present in preeclampsia, a life-threatening disease for both mother and child, are discussed to be involved in its pathogenesis or severity. (uzh.ch)
  • Additionally, failure of the clinical trial for the HDL-raising cholesteryl ester transfer protein inhibitor torcetrapid has recently been associated with off-target elevations of plasma aldosterone that correlated with increased atherosclerosis, ischemia, and death ( 8 , 9 ). (diabetesjournals.org)