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.
Aldosterone
Steroid 11-beta-Hydroxylase
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).
Fadrozole
Hypoaldosteronism
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.
Hyperaldosteronism
19-Iodocholesterol
19-Iodocholest-5-en-3 beta-ol. A cholesterol derivative usually substituted with radioactive iodine in the 19 position. The compound is an adrenal cortex scanning agent used in the assessment of patients suspected of having Cushing's syndrome, hyperaldosteronism, pheochromocytoma and adrenal remnants following total adrenalectomy.
Receptors, Mineralocorticoid
Mineralocorticoid Receptor Antagonists
Spironolactone
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)
Adrenal Glands
Adrenal Cortex
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.
Mineralocorticoids
A group of CORTICOSTEROIDS primarily associated with water and electrolyte balance. This is accomplished through the effect on ION TRANSPORT in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by PLASMA VOLUME, serum potassium, and ANGIOTENSIN II.
Zona Glomerulosa
Renin-Angiotensin System
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.
Renin
Steroid Hydroxylases
Angiotensin II
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.
Hypertension
Polymorphism, Genetic
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.
Corticosterone
Nuclear Receptor Subfamily 4, Group A, Member 2
Angiotensinogen
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.
Adrenocorticotropic Hormone
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).
Hydrocortisone
Genotype
Cytochrome P-450 Enzyme System
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.
Citrate (si)-Synthase
RNA, Messenger
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.
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) Hypoaldosteronism refers to a condition where the adrenal glands do not produce enough aldosterone, a hormone that helps regulate the balance of fluids and electrolytes in the body. This can lead to symptoms such as low blood pressure, dehydration, and electrolyte imbalances.
There are several possible causes of hypoaldosteronism, including:
1. Adrenal gland disorders: Damage to the adrenal glands, such as from injury or infection, can lead to a decrease in aldosterone production.
2. Genetic mutations: Some people may be born with genetic mutations that affect the production of aldosterone.
3. Autoimmune disorders: In some cases, the immune system may attack the adrenal glands and disrupt aldosterone production.
4. Medications: Certain medications, such as steroids and diuretics, can suppress the production of aldosterone.
5. Primary aldosteronism: This is a condition where the adrenal glands produce too much aldosterone, leading to an imbalance in electrolytes and fluids.
Treatment for hypoaldosteronism will depend on the underlying cause of the condition. In some cases, medications such as salt substitutes or diuretics may be prescribed to help manage symptoms. In other cases, hormone replacement therapy may be necessary to replace the missing aldosterone.
It is important to note that hypoaldosteronism can lead to more serious complications if left untreated, such as dehydration, electrolyte imbalances, and heart arrhythmias. If you suspect you may have hypoaldosteronism, it is important to consult with a healthcare professional for proper diagnosis and treatment.
Hyperaldosteronism refers to a condition where there is an excessive production of aldosterone, a hormone produced by the adrenal glands that helps regulate electrolyte balance and blood pressure. The condition can be caused by a variety of factors, including genetic mutations, primary aldosteronom excess syndrome, or secondary causes such as adrenal adenomas or carcinomas.
Symptoms of hyperaldosteronism may include high blood pressure, low potassium levels, muscle weakness, and heart arrhythmias. Treatment options vary depending on the underlying cause but may include medications to reduce aldosterone production, dietary modifications, and in some cases, surgery or radiation therapy.
It is important for individuals with hyperaldosteronism to receive regular monitoring and treatment from a healthcare provider to manage their condition effectively and prevent complications such as heart disease and stroke.
Hypertension (HTN) is a condition where the blood pressure in your arteries is elevated. It is a major risk factor for heart disease, stroke, and other cardiovascular conditions. Hypertension is defined as a systolic blood pressure of 140 mmHg or higher, a diastolic blood pressure of 90 mmHg or higher, or both.
There are two types of hypertension:
1. Primary Hypertension: This type of hypertension has no identifiable cause and is also known as essential hypertension. It accounts for about 90% of all cases of hypertension.
2. Secondary Hypertension: This type of hypertension is caused by an underlying medical condition or medication. It accounts for about 10% of all cases of hypertension.
Some common causes of secondary hypertension include:
* Kidney disease
* Adrenal gland disorders
* Hormonal imbalances
* Certain medications
* Sleep apnea
* Cocaine use
There are also several risk factors for hypertension, including:
* Age (the risk increases with age)
* Family history of hypertension
* Obesity
* Lack of exercise
* High sodium intake
* Low potassium intake
* Stress
Hypertension is often asymptomatic, and it can cause damage to the blood vessels and organs over time. Some potential complications of hypertension include:
* Heart disease (e.g., heart attacks, heart failure)
* Stroke
* Kidney disease (e.g., chronic kidney disease, end-stage renal disease)
* Vision loss (e.g., retinopathy)
* Peripheral artery disease
Hypertension is typically diagnosed through blood pressure readings taken over a period of time. Treatment for hypertension may include lifestyle changes (e.g., diet, exercise, stress management), medications, or a combination of both. The goal of treatment is to reduce the risk of complications and improve quality of life.
Aldosterone 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 ...
Aminoglutethimide
Aldosterone synthase (18-hydroxylase; CYP11B2). Prevents the conversion of corticosterone into aldosterone. As such, AG is an ... Aldosterone synthase inhibitors, Anticonvulsants, Antiglucocorticoids, Aromatase inhibitors, Cholesterol side-chain cleavage ...
Steroid 11β-hydroxylase
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): ...
Progesterone
"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 ... 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 ...
18-Hydroxycorticosterone
... 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 ...
11β-Hydroxyprogesterone
... 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 ...
Aldosterone
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... Aldosterone synthase is absent in other sections of the adrenal gland.[citation needed] Aldosterone synthesis is stimulated by ... The last parts are mediated either 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. Aldosterone is the ...
CAMK1
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/ ...
Corticosterone
... 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. ...
Familial hyperaldosteronism
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 ...
Adrenal gland
... 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 ...
Zona glomerulosa
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 ...
Corticosteroid
... 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 ...
Ethyl caffeate
"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 ...
Osilodrostat
It specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β- ... Aldosterone synthase inhibitors, Antiglucocorticoids, Fluoroarenes, Imidazoles, Nitriles, Novartis brands, Orphan drugs, ...
18-Hydroxycortisol
Cortisol 18-Hydroxycorticosterone Aldosterone synthase Steroid 11β-hydroxylase 6β-Hydroxycortisol Lenders J, Williams T, ... Increased synthesis is also found in patients with aldosterone-producing adenomas. ACTH stimulation test increases urinary ...
Steroidogenesis inhibitor
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 ...
CYP11 family
... and Aldosterone synthase (CYP11B2). CYP11 can be divided into A to E five subfamilies, and CYP11A are the ohonologues to CYP11C ...
Apparent mineralocorticoid excess syndrome
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 ...
Glucocorticoid remediable aldosteronism
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 ...
18-Hydroxy-11-deoxycorticosterone
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, ...
11-Deoxycorticosterone
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 ...
Adrenal cortex
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. ...
Metabotropic glutamate receptor
... downregulating aldosterone synthase, CYP11B1, and the production of adrenal steroids (i.e. aldosterone and cortisol). The first ...
Ketoconazole
Aldosterone synthase inhibitors, Antifungals for dermatologic use, Antiglucocorticoids, Aromatase inhibitors, Belgian ... and aldosterone, as well as vitamin D. Ketoconazole has been found to displace dihydrotestosterone and estradiol from sex ...
Mitotane
... aldosterone synthase, CYP11B2), and 3β-hydroxysteroid dehydrogenase (3β-HSD) to a lesser extent. In addition, mitotane has ... Aldosterone synthase inhibitors, Antiglucocorticoids, Antineoplastic drugs, Chloroarenes, Cholesterol side-chain cleavage ...
List of MeSH codes (D12.776)
... 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 ...
Secondary hypertension
... 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. ...
Steroidogenic enzyme
... aldosterone synthase) - mineralocorticoid synthesis 21-Hydroxylase - corticosteroid synthesis Cytochrome P450 (CYP1, 2, 3) - ...
Mespirenone
Aldosterone synthase inhibitors, Antimineralocorticoids, Cyclopropanes, Pregnanes, Spiro compounds, Spirolactones, Steroidal ... Nishino Y, Schröder H, el Etreby MF (1988). "Experimental studies on the endocrine side effects of new aldosterone antagonists ... Opoku J, Kalimi M, Agarwal M, Qureshi D (1991). "Effect of a new mineralocorticoid antagonist mespirenone on aldosterone- ... Weindel K, Lewicka S, Vecsei P (1991). "Inhibitory effects of the novel anti-aldosterone compound mespirenone on adrenocortical ...
Andrée Marquet
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, ...
Arginine
Andrew PJ, Mayer B (August 1999). "Enzymatic function of nitric oxide synthases". (review). Cardiovascular Research. 43 (3): ... Journal of the Renin-Angiotensin-Aldosterone System. 15 (1): 88-96. doi:10.1177/1470320313475910. PMID 23435582. Liu P, Jing Y ...
Pharmacodynamics of progesterone
It has 1000% of the affinity of aldosterone, the major endogenous agonist, for the human MR, and 100% of the affinity of ... "Progestins overcome inhibition of platelet aggregation by endothelial cells by down-regulating endothelial NO synthase via ... It does not affect aldosterone synthesis, blood pressure, carbohydrate metabolism or mood changes. No side effects have been ... An active metabolite of progesterone, 11-deoxycorticosterone (21-hydroxyprogesterone), is a precursor of aldosterone and has ...
Pregnenolone
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 ...
Cholesterol
Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic ... including the adrenal gland hormones cortisol and aldosterone, as well as the sex hormones progesterone, estrogens, and ...
Fasudil
Endothelial nitric oxide synthase (eNOS) mediates the production of the vasodilator nitric oxide (NO). Pulmonary arterial cell ... Ang-II is a peptide hormone which increases blood pressure by initiating vasoconstriction and aldosterone secretion. ROCK ... "Rho-kinase mediates hypoxia-induced downregulation of endothelial nitric oxide synthase". Circulation. 106 (1): 57-62. doi: ...
Index of biology articles
ATP synthase - atrioventricular valve - atrium - autoimmune disease - autonomic nervous system - autosome - auxins - axillary ... aldosterone - algae - allantois - allele - allometry - allopatric speciation - allosteric binding site - allosteric effector - ...
5-Hydroxyeicosatetraenoic acid
... in signaling for the secretion of aldosterone and progesterone, in triggering parturition, and in contributing to other ... be further metabolized either to leukotriene B4 by leukotriene A4 hydrolase or to leukotriene C4 by leukotriene C4 synthase. ...
Steroid
Squalene biosynthesis is catalyzed by squalene synthase, which belongs to the squalene/phytoene synthase family. Subsequent ... aldosterone, and testosterone are produced in the adrenal cortex.[citation needed] Estradiol, estrone and progesterone are made ... Aldosterone, a mineralocorticoid that helps regulate blood pressure through water and electrolyte balance Sex steroids: ...
HSD2 neuron
Unlike aldosterone-sensitive cells in epithelial tissues (e.g. in the kidney), the physiologic effects of aldosterone-MR ... nitric oxide synthase, cholecystokinin, neurotensin, neuropeptide FF, substance P, somatostatin, inhibin-β, glucagon-like ... It has been suggested, but not proven, that aldosterone promotes the firing activity of these neurons. Aldosterone is not ... cortisol effectively crowds out aldosterone in cells without abundant HSD2. In cells with HSD2, however, aldosterone has ...
Pharmacodynamics of spironolactone
... 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 Inhibitors as a Therapeutic Option for Patients With Resistant Hypertension | Consultant360
... which examined the use of the investigational aldosterone synthase inhibitor baxdrostat in patients with resistant hypertension ... Aldosterone Synthase Inhibitors as a Therapeutic Option for Patients With Resistant Hypertension ... Based on their mechanism of action, aldosterone synthase inhibitors block the actions of aldosterone without the off-target ... Aldosterone synthase inhibitors as a therapeutic option For patients with resistant hypertension. Consultant360. Published ...
Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice.
Measured haplotype analysis of the aldosterone synthase gene and heart size (European Journal of Human Genetics (2003) vol. 11 ...
Association between Aldosterone Synthase (|i|CYP11B2|/i|) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of...
Association between Aldosterone Synthase (,i,CYP11B2,/i,) Gene Polymorphism and Hypertensi Association between Aldosterone ... Aldosterone synthase (encoded by the CYP11B2 gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has ... In essential hypertension, the aldosterone synthase gene (CYP11B2) plays a significant role. Aldosterone synthesis is affected ... Aldosterone synthase (CYP11B2) was thoroughly studied in different ethnic groups; however, no such study has been conducted in ...
CYP11B2 gene: MedlinePlus Genetics
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 ( ...
baxdrostat Archives - Hospital Healthcare Europe
One therapeutic target in hypertension is aldosterone synthase and a new class of drugs, the aldosterone synthase inhibitors, ... One such agent is baxdrostat and which has been shown in preclinical studies to completely suppress aldosterone production in ... humans without affecting cortisol production. Nevertheless, whether reducing aldosterone would also lower blood pressure was ...
Around the nation: AstraZeneca to acquire CinCor Pharma for $1.8B
Report of Foreign Issuer Pursuant to Rule 13a-16 or 15d-16 (6-k)
... oral small molecule inhibitor of aldosterone synthase, the enzyme responsible for the synthesis of aldosterone in the adrenal ... Baxdrostat selectively targets aldosterone synthase, which is encoded by the CYP11B2 gene while having a much lower affinity ... Baxdrostat represents a potentially leading next-generation ASI as it is highly selective for aldosterone synthase and spares ... 3. CinCor Pharma Announces Topline Data for Phase 2 HALO Trial Evaluating Selective Aldosterone Synthase Inhibitor Baxdrostat ...
DeCS
Aldosterone synthase Aldosterone synthase cytochrome P-450 Aldostérone synthase Aldostérone synthétase Aldosynthase CYP 11B2 ... Aldosterone synthase. Aldosterone synthase cytochrome P-450. Aldostérone synthase. Aldostérone synthétase. Aldosynthase. CYP ... is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE.. ...
Vol. 13 No. 5 (2017)
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Human Genome Epidemiology Literature Finder|Home|PHGKB
Clinical Trials • BioPharma Media
The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats | BMC Genomics | Full...
... the enhanced biosynthesis of aldosterone in the brain stem of ISIAH rats was proposed. Multiple DEGs associated with several ... qPCR measurement of mRNA for the Cyp11b1 and Cyp11b2 genes encoding for the 11β-hydroxylase and aldosterone synthase enzymes, ... particularly aldosterone synthesis. According to the pathway analysis in the KEGG database, the aldosterone synthesis and ... The enhanced brain aldosterone may upregulate the sympathetic nervous activity [20]. It was demonstrated that the small amounts ...
DeCS 2008 - versión 17 de Marzo de 2008
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Mild-Regulated allosteric change allows temporal and subcellular management of enzyme exercise - Transgenic News room
Corticosterone is converted to aldosterone by aldosterone synthase, found only in the mitochondria of glomerulosa cells. ... and fatty acid synthase (FAS), was carried out using tissue microarrays from 102 resected SCCHN tumors. ... potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone. ...
Human Genome Epidemiology Literature Finder|Home|PHGKB
Bluebird, FDA, Resilience, Corvia, Code, Mineralys, Tessa
Glutamic acid - Wikipedia
Mineralys Reports Q12023 Financial Results - Ysios Capital
Lorundrostat has 374-fold selectivity for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro and an ... Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the ... Its initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase ... Abnormally elevated aldosterone levels are a key factor in driving hypertension in approximately 25 percent of all hypertensive ...
Secondary Hypertension - FindZebra
... 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 Conns disease, an adrenocortical tumor which causes excess release of aldosterone, that ... DOC has blood-pressure raising effects similar to aldosterone, and abnormally high levels result in hypokalemic hypertension. ... At high concentrations cortisol can cross-react and activate the mineralocorticoid receptor, leading to aldosterone-like ...
antibodies bind to - ELISA Strip
biology cells quiz 3 - Scalegenomics
Human H1(Histone H1) ELISA Kit - The International Society for Microbiology
Braz J Med Biol Res - Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions
7. White KA & Marletta MA (1992). Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry, 31: 6627-6631.. ... 9. Raff H & Jankowski B (1994). Inhibition of aldosterone release by hypoxia in vitro: interaction with carbon monoxide. ... Since carbon monoxide has been shown to compete with L-arginine for binding to nitric oxide synthase, then L-arginine may ... Klatt P, Schmidt K & Mayer B (1992). Brain nitric oxide synthase is a haemoprotein. Biochemical Journal, 288: 15-17.. ...
Angiotensin converting enzyme inhibitors. Medical search. Definitions
AgentsPhenylmethylsulfonyl FluorideCyclooxygenase InhibitorsAcrylatesProstaglandinsProtein Kinase CAldosterone Synthase ... Nitric Oxide Synthase. An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE ... Aldosterone. A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal ... A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the ...
Research Grants 14/07947-6 - Endotélio vascular, Músculo liso vascular - BV FAPESP
In isolated aorta and PVAT from treated rats, as well as in the cultured cells, it will be evaluated: aldosterone and ... Spironolactone Prevents Endothelial Nitric Oxide Synthase Uncoupling and Vascular Dysfunction Induced by beta-Adrenergic ... smooth muscle and adipose cells express functional beta-AR e MR and the enzymes to synthesize aldosterone and glucocorticoids, ... could the chronic beta-AR stimulation induce local synthesis of aldosterone and/or glucocorticoids, or even modulate their ...
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Publications: Stavroula Kanoni
Endothelial nitric oxide synthase gene polymorphisms - 786T > C and 894G > T in coronary artery bypass graft surgery ... Renin-angiotensin-aldosterone system gene polymorphisms in coronary artery bypass graft surgery patients . J Renin Angiotensin ... Endothelial nitric oxide synthase gene polymorphisms -786T , C and 894G , T in coronary artery bypass graft surgery patients . ... Endothelial nitric oxide synthase gene polymorphisms -786T >C and 894G >Tin coronary artery bypass graft surgery patients ...
CYP11B214
- CYP11B2, the gene encoding aldosterone synthase (P450c11Aldo), is expressed in the zona glomerulosa under primary control of the renin-angiotensin system. (nih.gov)
- Mutations in CYP11B2 cause congenital hypoaldosteronism (aldosterone synthase deficiency) which is characterized by life-threatening salt loss, failure to thrive, hyponatraemia and hyperkalaemia in early infancy. (nih.gov)
- Inhibition of aldosterone synthase (CYP11B2) by torasemide prevents atrial fibrosis and atrial fibrillation in mice. (helmholtz-hzi.de)
- The CYP11B2 gene mutations that cause corticosterone methyloxidase deficiency 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)
- 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)
- 6. Haplotype association and synergistic effect of human aldosterone synthase (CYP11B2) gene polymorphisms causing susceptibility to essential hypertension in Indian patients. (nih.gov)
- 9. Association of aldosterone synthase CYP11B2 (-344C/T) gene polymorphism with essential hypertension and left ventricular hypertrophy in the Egyptian population. (nih.gov)
- 10. Association of DNA polymorphisms within the CYP11B2/CYP11B1 locus and postoperative hypertension risk in the patients with aldosterone-producing adenomas. (nih.gov)
- 12. Haplotype analysis of aldosterone synthase gene (CYP11B2) polymorphisms shows association with essential hypertension. (nih.gov)
- 15. [Association of aldosterone synthase (CYP11B2) gene -344T/C polymorphism with essential hypertension in Mongolian nationality]. (nih.gov)
- 17. [Promoter variants of aldosterone synthase gene (CYP11B2) and salt-sensitivity of blood pressure]. (nih.gov)
- Esta enzima, codificada por el gen CYP11B2, es importante en la conversión de la CORTICOSTERONA en 18-hidroxicorticosterona y la subsiguiente conversión en ALDOSTERONA. (bvsalud.org)
- This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE. (bvsalud.org)
- To examine the effects of LRH on steroidogenic capacity we used reporter constructs prepared with the 5'-flanking region of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage (CYP11A1), 3beta hydroxysteroid dehydrogenase type II (HSD3B2), 17alpha hydroxylase, 17,20 lyase (CYP17), 11beta hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2). (bioscientifica.com)
Inhibitor8
- The recently published BrightHTN study examined the use of the investigational aldosterone synthase inhibitor baxdrostat in patients with resistant hypertension. (cdhub360.com)
- An investigational aldosterone synthase inhibitor could be an effective new treatment to reduce blood pressure in patients with treatment-resistant hypertension, a phase 2 study suggests. (medscape.com)
- According to Fierce Biotech , 'CinCor traded above $30 throughout much of the fall of 2022, only to plummet precipitously in late November when the biotech shared phase 2 data on aldosterone synthase inhibitor baxdrostat in uncontrolled hypertension. (advisory.com)
- The acquisition will bolster AstraZeneca's cardiorenal pipeline by adding CinCor's candidate drug, baxdrostat (CIN-107), an aldosterone synthase inhibitor (ASI) for blood pressure lowering in treatment-resistant hypertension. (advfn.com)
- Baxdrostat is a highly selective, oral small molecule inhibitor of aldosterone synthase, the enzyme responsible for the synthesis of aldosterone in the adrenal gland, in development for patient populations with significant unmet medical needs, including treatment-resistant hypertension, primary aldosteronism and chronic kidney disease. (advfn.com)
- A selective aldosterone synthase inhibitor for significantly lowering blood pressure. (biopharma.media)
- Mineralys plans to use the proceeds to continue to advance MLS-101, a highly selective aldosterone synthase inhibitor. (european-biotechnology.com)
- MLS-101, the target of desire, once licensed from Mitsubishi Tanabe Pharma Corporation, is a highly selective and potent aldosterone synthase inhibitor. (european-biotechnology.com)
Hypertension10
- The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes . (bvsalud.org)
- 3. A novel haplotype of low-frequency variants in the aldosterone synthase gene among northern Han Chinese with essential hypertension. (nih.gov)
- 16. Association of the -344T/C aldosterone synthase gene variant with essential hypertension. (nih.gov)
- It seems to have a bright future in the area of resistant hypertension, particularly in patients who are producing too much aldosterone," said Suzanne Oparil, MD, invited discussant for the study and director of the Vascular Biology and Hypertension program at the University of Alabama at Birmingham. (medscape.com)
- She noted that aldosterone is a major contributor to the pathogenesis of resistant hypertension, which afflicts about 20% of the hypertensive population. (medscape.com)
- Aldosterone antagonists are considered by many to be the best add-on treatment for resistant hypertension and do lower blood pressure. (medscape.com)
- One therapeutic target in hypertension is aldosterone synthase and a new class of drugs, the aldosterone synthase inhibitors, are currently under development. (hospitalhealthcare.com)
- Mutations and overexpression of P450 11B2 (also known as aldosterone synthase) can lead to hypertension, congestive heart failure, and diabetic nephropathy. (nih.gov)
- Excess levels of aldosterone are associated with hypertension and several cardiorenal diseases, including chronic kidney disease and coronary artery disease and being able to effectively reduce this would offer a much-needed treatment option for these patients. (advfn.com)
- We are pleased to be joined by a strong, international group of investors who share our vision of creating a targeted approach to address the growing epidemic of abnormal aldosterone overproduction, that is linked to uncontrolled hypertension and related cardiorenal disorders. (european-biotechnology.com)
Known as aldosterone synthase1
- 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)
Inhibitors2
- Based on their mechanism of action, aldosterone synthase inhibitors block the actions of aldosterone without the off-target steroid receptor effects of gynecomastia in men and menstrual irregularities and post-menopausal bleeding in women that are sometimes seen with spironolactone and to a lesser extent eplerenone (which is a more selective MRA) but should share the same risks of azotemia and electrolyte disturbances as these established therapies. (cdhub360.com)
- Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted. (medunigraz.at)
Baxdrostat3
- As expected, the baxdrostat groups had a decrease in plasma aldosterone levels and a compensatory increase in plasma renin activity. (cdhub360.com)
- Baxdrostat, however, is able to selectively block aldosterone synthase, and thus the production of aldosterone, without also blocking the production of cortisol, explained Mason W. Freeman, MD, lead author of the study and executive vice president of clinical development at CinCor Pharma, which is developing the agent. (medscape.com)
- Over 12 weeks of follow-up in the new study, the use of baxdrostat led to decreases in serum aldosterone levels ranging from 3.0 ng/dL with the 0.5-mg dose to 4.9 ng/dL with the 2-mg dose. (medscape.com)
Cortisol3
- In humans, two cytochrome P450 isoenzymes with 11beta-hydroxylase activity, catalysing the biosynthesis of cortisol and aldosterone, are present in the adrenal cortex. (nih.gov)
- What's made this extraordinarily difficult is that the enzyme that makes aldosterone synthase and the enzyme required for cortisol synthase, 11-beta-hydroxylase, are 93% sequence similar. (medscape.com)
- As with the Target-HTN trial, lorundrostat was well-tolerated and had the predicted effect of suppressing aldosterone in a dose-dependent fashion without inhibiting cortisol. (ysioscapital.com)
11beta-hydroxylase1
- Aldosterone synthase has 11beta-hydroxylase activity as well as 18-hydroxylase activity and 18-oxidase activity. (nih.gov)
Enzyme4
- 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)
- 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)
- We found that although aldosterone is produced processively, the enzyme preferentially utilizes a distributive mechanism that ends with the production of 18-OH corticosterone. (nih.gov)
11B24
- 7. The cytochrome 11B2 aldosterone synthase gene rs1799998 single nucleotide polymorphism determines elevated aldosterone, higher blood pressure, and reduced glomerular filtration, especially in diabetic female patients. (nih.gov)
- Human cytochrome P450 11B2 produces aldosterone by a processive mechanism due to the lactol form of the intermediate 18-hydroxycorticosterone. (nih.gov)
- Human cytochrome P450 (P450) 11B2 catalyzes the formation of aldosterone, the major endogenous human mineralocorticoid. (nih.gov)
- P450 11B2 catalyzes aldosterone formation from 11-deoxycorticosterone through three distinct oxidation steps. (nih.gov)
Mineralocorticoid3
- Inhibition of aldosterone synthesis has been proposed as a potential alternative to blocking the mineralocorticoid receptor. (cdhub360.com)
- For at least 20 years, researchers have tried to create a drug that would lower aldosterone levels directly by inhibiting hormone synthesis rather than blocking the mineralocorticoid receptor. (medscape.com)
- MLS-101 has the potential to be a paradigm-shifting treatment by normalizing plasma aldosterone levels, selectively, without the untoward effects of blocking the mineralocorticoid receptor. (european-biotechnology.com)
Mutations3
- Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. (endocrine-abstracts.org)
- Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. (endocrine-abstracts.org)
- However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. (endocrine-abstracts.org)
Deficiency1
- Aldosterone synthase deficiency type I: hormonal and genetic analyses of two cases. (medlineplus.gov)
Biosynthesis1
- In accordance with the functional annotation of DEGs, the key role of hormonal metabolic processes and, in particular, the enhanced biosynthesis of aldosterone in the brain stem of ISIAH rats was proposed. (biomedcentral.com)
Susceptibility2
- Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease. (bvsalud.org)
- Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients . (bvsalud.org)
Hormone2
- Aldosterone synthase helps produce a hormone called aldosterone. (medlineplus.gov)
- If you have low levels of the hormone aldosterone , cannot urinate freely because of an obstruction, or had a kidney transplant , you are more likely to develop type 4 RTA. (nih.gov)
Blood pressure2
- Aldosterone regulates blood pressure by maintaining proper salt and fluid levels in the body. (medlineplus.gov)
- Nevertheless, whether reducing aldosterone would also lower blood pressure was unclear and the subject of the current study. (hospitalhealthcare.com)
Patients2
- Aldosterone-to-Renin Ratio Is Associated With Reduced 24-Hour Heart Rate Variability and QTc Prolongation in Hypertensive Patients. (medunigraz.at)
- The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients. (cdc.gov)
Protein1
- Microvascular dysfunction was associated with elevated expression of myocardial endothelin, inducible NO synthase (NOS) protein and 3-nitrotyrosine. (bvsalud.org)
Levels1
- The 24-hour urinary aldosterone levels decreased with all three doses tested. (medscape.com)
Clinical1
- Mineralys Therapeutics, Inc. (Nasdaq: MLYS), a clinical-stage biopharmaceutical company focused on developing medicines to target diseases driven by abnormally elevated aldosterone, today announced financial results for the quarter ending March 31, 2023, and provided a corporate update. (ysioscapital.com)
Cells1
- This database provides median FPKM values for the transcriptome of renal late distal convoluted tubule (DCT2) cells /connecting tubule (CNT) cells/initial cortical collecting duct (iCCD) principal cells from TRPV5 eGFP male mice treated with vehicle or aldosterone for 6 days. (nih.gov)
Effects1
- Aldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. (medunigraz.at)
Gene3
- In the fusion gene, ACTH binding abnormally triggers production of aldosterone synthase. (medlineplus.gov)
- Aldosterone synthase gene polymorphism as a determinant of atrial fibrillation in patients with heart failure. (medlineplus.gov)
- This gene provides instructions for making an enzyme called aldosterone synthase. (nih.gov)
Mutations1
- 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)
Deoxycorticosterone3
- 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)
- Deoxycorticosterone (DOC) is a C-21 (21 carbon atoms) steroid hormone 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)
- P450 11B2 catalyzes aldosterone formation from 11-deoxycorticosterone through three distinct oxidation steps. (nih.gov)
Regulation1
- Aldosterone is important for the regulation of electrolyte homeostasis. (nih.gov)
Adrenal2
- 14. Zone-specific expression of aldosterone synthase cytochrome P-450 and cytochrome P-45011 beta in rat adrenal cortex: histochemical basis for the functional zonation. (nih.gov)
- 16. Development of adrenal zonation in fetal rats defined by expression of aldosterone synthase and 11beta-hydroxylase. (nih.gov)
Type1
- 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). (msdmanuals.com)
