Aldosterone Synthase
Aldosterone
Steroid 11-beta-Hydroxylase
Fadrozole
Hypoaldosteronism
Hyperaldosteronism
19-Iodocholesterol
Receptors, Mineralocorticoid
Mineralocorticoid Receptor Antagonists
Spironolactone
Adrenal Glands
Adrenal Cortex
Mineralocorticoids
Zona Glomerulosa
Renin-Angiotensin System
Renin
Steroid Hydroxylases
Angiotensin II
Hypertension
Polymorphism, Genetic
Corticosterone
Nuclear Receptor Subfamily 4, Group A, Member 2
Angiotensinogen
Adrenocorticotropic Hormone
Hydrocortisone
Genotype
Cytochrome P-450 Enzyme System
Citrate (si)-Synthase
RNA, Messenger
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)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.
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.
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
Aminoglutethimide
Steroid 11β-hydroxylase
Progesterone
18-Hydroxycorticosterone
11β-Hydroxyprogesterone
Aldosterone
CAMK1
Corticosterone
Familial hyperaldosteronism
Adrenal gland
Zona glomerulosa
Corticosteroid
Ethyl caffeate
Osilodrostat
18-Hydroxycortisol
Steroidogenesis inhibitor
CYP11 family
Apparent mineralocorticoid excess syndrome
Glucocorticoid remediable aldosteronism
18-Hydroxy-11-deoxycorticosterone
11-Deoxycorticosterone
Adrenal cortex
Metabotropic glutamate receptor
Ketoconazole
Mitotane
List of MeSH codes (D12.776)
Secondary hypertension
Steroidogenic enzyme
Mespirenone
Andrée Marquet
Arginine
Pharmacodynamics of progesterone
Pregnenolone
Cholesterol
Fasudil
Index of biology articles
5-Hydroxyeicosatetraenoic acid
Steroid
HSD2 neuron
Pharmacodynamics of spironolactone
Aldosterone Synthase Inhibitors as a Therapeutic Option for Patients With Resistant Hypertension | Consultant360
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...
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baxdrostat Archives - Hospital Healthcare Europe
Around the nation: AstraZeneca to acquire CinCor Pharma for $1.8B
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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)