A mitochondrial cytochrome P450 enzyme that catalyzes the 18-hydroxylation of steroids in the presence of molecular oxygen and NADPH-specific flavoprotein. This enzyme, encoded by CYP11B2 gene, is important in the conversion of CORTICOSTERONE to 18-hydroxycorticosterone and the subsequent conversion to ALDOSTERONE.
A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
A mitochondrial cytochrome P450 enzyme that catalyzes the 11-beta-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11B1 gene, is important in the synthesis of CORTICOSTERONE and HYDROCORTISONE. Defects in CYP11B1 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
A congenital or acquired condition of insufficient production of ALDOSTERONE by the ADRENAL CORTEX leading to diminished aldosterone-mediated synthesis of Na(+)-K(+)-EXCHANGING ATPASE in renal tubular cells. Clinical symptoms include HYPERKALEMIA, sodium-wasting, HYPOTENSION, and sometimes metabolic ACIDOSIS.
A condition caused by the overproduction of ALDOSTERONE. It is characterized by sodium retention and potassium excretion with resultant HYPERTENSION and HYPOKALEMIA.
11 beta,18,21-Trihydroxypregn-4-ene-3,20-dione.
Cytoplasmic proteins that specifically bind MINERALOCORTICOIDS and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA.
Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.
A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.
The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.
A group of CORTICOSTEROIDS primarily associated with water and electrolyte balance. This is accomplished through the effect on ION TRANSPORT in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by PLASMA VOLUME, serum potassium, and ANGIOTENSIN II.
The narrow subcapsular outer zone of the adrenal cortex. This zone produces a series of enzymes that convert PREGNENOLONE to ALDOSTERONE. The final steps involve three successive oxidations by CYTOCHROME P-450 CYP11B2.
A BLOOD PRESSURE regulating system of interacting components that include RENIN; ANGIOTENSINOGEN; ANGIOTENSIN CONVERTING ENZYME; ANGIOTENSIN I; ANGIOTENSIN II; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming ANGIOTENSIN I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to ANGIOTENSIN II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal VASCULAR SMOOTH MUSCLE, leading to retention of salt and water in the KIDNEY and increased arterial blood pressure. In addition, angiotensin II stimulates the release of ALDOSTERONE from the ADRENAL CORTEX, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down BRADYKININ, a powerful vasodilator and component of the KALLIKREIN-KININ SYSTEM.
A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.
Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
An orphan nuclear receptor that is found at high levels in BRAIN tissue. The protein is believed to play a role in development and maintenance of NEURONS, particularly dopaminergic neurons.
An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver and secreted into blood circulation. Angiotensinogen is the inactive precursor of natural angiotensins. Upon successive enzyme cleavages, angiotensinogen yields angiotensin I, II, and III with amino acids numbered at 10, 8, and 7, respectively.
An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Enzyme that catalyzes the first step of the tricarboxylic acid cycle (CITRIC ACID CYCLE). It catalyzes the reaction of oxaloacetate and acetyl CoA to form citrate and coenzyme A. This enzyme was formerly listed as EC 4.1.3.7.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

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)

Aldosterone synthase is a steroidogenic enzyme that is primarily responsible for the production of the hormone aldosterone in the adrenal gland. It is encoded by the CYP11B2 gene and is located within the mitochondria of the zona glomerulosa cells in the adrenal cortex.

Aldosterone synthase catalyzes two key reactions in the biosynthesis of aldosterone: the conversion of corticosterone to 18-hydroxycorticosterone and the subsequent conversion of 18-hydroxycorticosterone to aldosterone. These reactions involve the sequential addition of hydroxyl groups at the C18 position of the steroid molecule, which is a critical step in the synthesis of aldosterone.

Aldosterone plays an important role in regulating blood pressure and electrolyte balance by increasing the reabsorption of sodium and water in the distal nephron of the kidney, while promoting the excretion of potassium. Disorders of aldosterone synthase can lead to conditions such as primary hyperaldosteronism, which is characterized by excessive production of aldosterone and can result in hypertension and hypokalemia.

Aldosterone is a hormone produced by the adrenal gland. It plays a key role in regulating sodium and potassium balance and maintaining blood pressure through its effects on the kidneys. Aldosterone promotes the reabsorption of sodium ions and the excretion of potassium ions in the distal tubules and collecting ducts of the nephrons in the kidneys. This increases the osmotic pressure in the blood, which in turn leads to water retention and an increase in blood volume and blood pressure.

Aldosterone is released from the adrenal gland in response to a variety of stimuli, including angiotensin II (a peptide hormone produced as part of the renin-angiotensin-aldosterone system), potassium ions, and adrenocorticotropic hormone (ACTH) from the pituitary gland. The production of aldosterone is regulated by a negative feedback mechanism involving sodium levels in the blood. High sodium levels inhibit the release of aldosterone, while low sodium levels stimulate its release.

In addition to its role in maintaining fluid and electrolyte balance and blood pressure, aldosterone has been implicated in various pathological conditions, including hypertension, heart failure, and primary hyperaldosteronism (a condition characterized by excessive production of aldosterone).

Steroid 11-beta-hydroxylase is a crucial enzyme involved in the steroidogenesis pathway, specifically in the synthesis of cortisol and aldosterone, which are vital hormones produced by the adrenal glands. This enzyme is encoded by the CYP11B1 gene in humans.

The enzyme's primary function is to catalyze the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to aldosterone through the process of hydroxylation at the 11-beta position of the steroid molecule. Cortisol is a critical glucocorticoid hormone that helps regulate metabolism, immune response, and stress response, while aldosterone is a mineralocorticoid hormone responsible for maintaining electrolyte and fluid balance in the body.

Deficiencies or mutations in the CYP11B1 gene can lead to various disorders, such as congenital adrenal hyperplasia (CAH), which may result in impaired cortisol and aldosterone production, causing hormonal imbalances and associated symptoms.

Fadrozole is a non-steroidal aromatase inhibitor drug that is used in the treatment of breast cancer. Aromatase inhibitors work by blocking the production of estrogen, which some types of breast cancer cells need to grow. By reducing the amount of estrogen in the body, fadrozole can help slow or stop the growth of these cancer cells.

Fadrozole is typically used as a treatment for postmenopausal women with hormone receptor-positive breast cancer. It may be used as a first-line therapy or after other treatments have failed. The drug is administered orally, and the typical dosage is 1-2 mg per day.

Like all medications, fadrozole can cause side effects, including hot flashes, nausea, vomiting, and joint pain. In some cases, it may also cause more serious side effects such as liver damage or an increased risk of bone fractures. Patients taking fadrozole should be monitored closely by their healthcare provider to ensure that the drug is working effectively and to manage any side effects that may occur.

Hypoaldosteronism is a medical condition characterized by decreased levels or impaired function of the hormone aldosterone, which is produced by the adrenal gland. Aldosterone plays a crucial role in regulating electrolyte and fluid balance in the body by increasing the reabsorption of sodium and excretion of potassium in the kidneys.

Hypoaldosteronism can lead to low blood pressure, muscle weakness, and an imbalance of electrolytes, particularly low serum sodium levels and high serum potassium levels. This condition can be caused by various factors, including damage to the adrenal gland, impaired production or function of aldosterone, or decreased responsiveness of the kidneys to aldosterone.

Hypoaldosteronism can be primary or secondary. Primary hypoaldosteronism is caused by a problem with the adrenal glands themselves, such as damage to the gland or a genetic disorder that affects aldosterone production. Secondary hypoaldosteronism is caused by a problem outside of the adrenal glands, such as decreased production of renin (an enzyme produced by the kidneys) or certain medications that interfere with aldosterone production or function.

Treatment for hypoaldosteronism depends on the underlying cause and may include medication to replace missing aldosterone or correct electrolyte imbalances, as well as addressing any underlying conditions contributing to the development of the condition.

Hyperaldosteronism is a medical condition characterized by the overproduction of aldosterone, a hormone produced by the adrenal glands. Aldosterone helps regulate sodium and potassium balance and blood pressure by promoting sodium retention and potassium excretion in the kidneys.

There are two types of hyperaldosteronism: primary and secondary. Primary hyperaldosteronism is caused by an overproduction of aldosterone from an abnormality within the adrenal gland, such as a tumor (Conn's syndrome) or hyperplasia. Secondary hyperaldosteronism occurs when there is an excess production of renin, a hormone produced by the kidneys, which then stimulates the adrenal glands to produce more aldosterone. This can be caused by various conditions that affect kidney function, such as renal artery stenosis or heart failure.

Symptoms of hyperaldosteronism may include high blood pressure, low potassium levels (hypokalemia), muscle weakness, and frequent urination. Diagnosis typically involves measuring aldosterone and renin levels in the blood, as well as other tests to determine the underlying cause. Treatment depends on the type and cause of hyperaldosteronism but may include medications, surgery, or lifestyle changes.

18-Hydroxycorticosterone is a steroid hormone that is produced in the adrenal gland. It is an intermediate in the biosynthesis of aldosterone, which is the major hormone responsible for regulating sodium and potassium balance in the body. 18-Hydroxycorticosterone gets its name from the hydroxyl group (-OH) that is added to the 18th carbon atom of the steroid molecule.

This hormone plays a role in the body's response to stress and helps to regulate various physiological processes, including metabolism, immune function, and sexual development and reproduction. However, abnormal levels of 18-hydroxycorticosterone have been associated with certain medical conditions, such as primary aldosteronism, which is a condition characterized by the overproduction of aldosterone.

It's important to note that while 18-hydroxycorticosterone is an important hormone in the body, it is not typically measured in routine clinical testing. Instead, tests for aldosterone and related hormones are more commonly used to diagnose and manage conditions related to the adrenal gland.

Medical Definition:

Mineralocorticoid Receptors (MRs) are a type of nuclear receptor protein that are activated by the binding of mineralocorticoid hormones, such as aldosterone. These receptors are expressed in various tissues and cells, including the kidneys, heart, blood vessels, and brain.

When activated, MRs regulate gene expression related to sodium and potassium homeostasis, water balance, and electrolyte transport. This is primarily achieved through the regulation of ion channels and transporters in the distal nephron of the kidney, leading to increased sodium reabsorption and potassium excretion.

Abnormalities in mineralocorticoid receptor function have been implicated in several diseases, including hypertension, heart failure, and primary aldosteronism.

Mineralocorticoid receptor antagonists (MRAs) are a class of medications that block the action of aldosterone, a hormone produced by the adrenal glands. Aldosterone helps regulate sodium and potassium balance and blood pressure by binding to mineralocorticoid receptors in the kidneys, heart, blood vessels, and brain.

When aldosterone binds to these receptors, it promotes sodium retention and potassium excretion, which can lead to an increase in blood volume and blood pressure. MRAs work by blocking the binding of aldosterone to its receptors, thereby preventing these effects.

MRAs are primarily used to treat heart failure, hypertension, and kidney disease. By reducing sodium retention and increasing potassium excretion, MRAs can help lower blood pressure, reduce fluid buildup in the body, and improve heart function. Examples of MRAs include spironolactone and eplerenone.

Spironolactone is a prescription medication that belongs to a class of drugs known as potassium-sparing diuretics. It works by blocking the action of aldosterone, a hormone that helps regulate sodium and potassium balance in your body. This results in increased urine production (diuresis) and decreased salt and fluid retention.

Spironolactone is primarily used to treat edema (fluid buildup) associated with heart failure, liver cirrhosis, or kidney disease. It's also prescribed for the treatment of high blood pressure and primary hyperaldosteronism, a condition where the adrenal glands produce too much aldosterone.

Furthermore, spironolactone is used off-label to treat conditions such as acne, hirsutism (excessive hair growth in women), and hormone-sensitive breast cancer in postmenopausal women.

It's important to note that spironolactone can cause increased potassium levels in the blood (hyperkalemia) and should be used with caution in patients with kidney impairment or those taking other medications that affect potassium balance. Regular monitoring of electrolyte levels, including potassium and sodium, is essential during spironolactone therapy.

The adrenal glands are a pair of endocrine glands that are located on top of the kidneys. Each gland has two parts: the outer cortex and the inner medulla. The adrenal cortex produces hormones such as cortisol, aldosterone, and androgens, which regulate metabolism, blood pressure, and other vital functions. The adrenal medulla produces catecholamines, including epinephrine (adrenaline) and norepinephrine (noradrenaline), which help the body respond to stress by increasing heart rate, blood pressure, and alertness.

The adrenal cortex is the outer portion of the adrenal gland, which is located on top of the kidneys. It plays a crucial role in producing hormones that are essential for various bodily functions. The adrenal cortex is divided into three zones:

1. Zona glomerulosa: This outermost zone produces mineralocorticoids, primarily aldosterone. Aldosterone helps regulate sodium and potassium balance and thus influences blood pressure by controlling the amount of fluid in the body.
2. Zona fasciculata: The middle layer is responsible for producing glucocorticoids, with cortisol being the most important one. Cortisol regulates metabolism, helps manage stress responses, and has anti-inflammatory properties. It also plays a role in blood sugar regulation and maintaining the body's response to injury and illness.
3. Zona reticularis: The innermost zone produces androgens, primarily dehydroepiandrosterone (DHEA) and its sulfate form (DHEAS). These androgens are weak compared to those produced by the gonads (ovaries or testes), but they can be converted into more potent androgens or estrogens in peripheral tissues.

Disorders related to the adrenal cortex can lead to hormonal imbalances, affecting various bodily functions. Examples include Addison's disease (insufficient adrenal cortical hormone production) and Cushing's syndrome (excessive glucocorticoid levels).

Mineralocorticoids are a class of steroid hormones that primarily regulate electrolyte and fluid balance in the body. The most important mineralocorticoid is aldosterone, which is produced by the adrenal gland in response to signals from the renin-angiotensin system. Aldosterone acts on the distal tubules and collecting ducts of the nephrons in the kidneys to increase the reabsorption of sodium ions (Na+) and water into the bloodstream, while promoting the excretion of potassium ions (K+) and hydrogen ions (H+) into the urine. This helps maintain blood pressure and volume, as well as ensuring a proper balance of electrolytes in the body. Other mineralocorticoids include cortisol and corticosterone, which have weak mineralocorticoid activity and play a more significant role as glucocorticoids, regulating metabolism and immune response.

Zona glomerulosa is a region of the adrenal gland, specifically the outer portion of the adrenal cortex. It is responsible for producing mineralocorticoids, with the principal one being aldosterone. Aldosterone helps regulate electrolyte and fluid balance in the body by increasing the reabsorption of sodium ions and water in the distal nephron of the kidney while promoting the excretion of potassium ions. This process assists in maintaining blood pressure and volume within normal ranges. The zona glomerulosa's function is primarily under the control of the renin-angiotensin-aldosterone system (RAAS).

The Renin-Angiotensin System (RAS) is a complex hormonal system that regulates blood pressure, fluid and electrolyte balance, and vascular resistance. It plays a crucial role in the pathophysiology of hypertension, heart failure, and kidney diseases.

Here's a brief overview of how it works:

1. Renin is an enzyme that is released by the juxtaglomerular cells in the kidneys in response to decreased blood pressure or reduced salt delivery to the distal tubules.
2. Renin acts on a protein called angiotensinogen, which is produced by the liver, converting it into angiotensin I.
3. Angiotensin-converting enzyme (ACE), found in the lungs and other tissues, then converts angiotensin I into angiotensin II, a potent vasoconstrictor that narrows blood vessels and increases blood pressure.
4. Angiotensin II also stimulates the release of aldosterone from the adrenal glands, which promotes sodium and water reabsorption in the kidneys, further increasing blood volume and blood pressure.
5. Additionally, angiotensin II has direct effects on the heart, promoting hypertrophy and remodeling, which can contribute to heart failure.
6. The RAS can be modulated by various medications, such as ACE inhibitors, angiotensin receptor blockers (ARBs), and aldosterone antagonists, which are commonly used to treat hypertension, heart failure, and kidney diseases.

Renin is a medically recognized term and it is defined as:

"A protein (enzyme) that is produced and released by specialized cells (juxtaglomerular cells) in the kidney. Renin is a key component of the renin-angiotensin-aldosterone system (RAAS), which helps regulate blood pressure and fluid balance in the body.

When the kidney detects a decrease in blood pressure or a reduction in sodium levels, it releases renin into the bloodstream. Renin then acts on a protein called angiotensinogen, converting it to angiotensin I. Angiotensin-converting enzyme (ACE) subsequently converts angiotensin I to angiotensin II, which is a potent vasoconstrictor that narrows blood vessels and increases blood pressure.

Additionally, angiotensin II stimulates the adrenal glands to release aldosterone, a hormone that promotes sodium reabsorption in the kidneys and increases water retention, further raising blood pressure.

Therefore, renin plays a critical role in maintaining proper blood pressure and electrolyte balance in the body."

Steroid hydroxylases are enzymes that catalyze the addition of a hydroxyl group (-OH) to a steroid molecule. These enzymes are located in the endoplasmic reticulum and play a crucial role in the biosynthesis of various steroid hormones, such as cortisol, aldosterone, and sex hormones. The hydroxylation reaction catalyzed by these enzymes increases the polarity and solubility of steroids, allowing them to be further metabolized and excreted from the body.

The most well-known steroid hydroxylases are part of the cytochrome P450 family, specifically CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP19A1, and CYP21A2. Each enzyme has a specific function in steroid biosynthesis, such as converting cholesterol to pregnenolone (CYP11A1), hydroxylating the 11-beta position of steroids (CYP11B1 and CYP11B2), or performing multiple hydroxylation reactions in the synthesis of sex hormones (CYP17A1, CYP19A1, and CYP21A2).

Defects in these enzymes can lead to various genetic disorders, such as congenital adrenal hyperplasia, which is characterized by impaired steroid hormone biosynthesis.

Angiotensin II is a potent vasoactive peptide hormone that plays a critical role in the renin-angiotensin-aldosterone system (RAAS), which is a crucial regulator of blood pressure and fluid balance in the body. It is formed from angiotensin I through the action of an enzyme called angiotensin-converting enzyme (ACE).

Angiotensin II has several physiological effects on various organs, including:

1. Vasoconstriction: Angiotensin II causes contraction of vascular smooth muscle, leading to an increase in peripheral vascular resistance and blood pressure.
2. Aldosterone release: Angiotensin II stimulates the adrenal glands to release aldosterone, a hormone that promotes sodium reabsorption and potassium excretion in the kidneys, thereby increasing water retention and blood volume.
3. Sympathetic nervous system activation: Angiotensin II activates the sympathetic nervous system, leading to increased heart rate and contractility, further contributing to an increase in blood pressure.
4. Thirst regulation: Angiotensin II stimulates the hypothalamus to increase thirst, promoting water intake and helping to maintain intravascular volume.
5. Cell growth and fibrosis: Angiotensin II has been implicated in various pathological processes, such as cell growth, proliferation, and fibrosis, which can contribute to the development of cardiovascular and renal diseases.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are two classes of medications commonly used in clinical practice to target the RAAS by blocking the formation or action of angiotensin II, respectively. These drugs have been shown to be effective in managing hypertension, heart failure, and chronic kidney disease.

Hypertension is a medical term used to describe abnormally high blood pressure in the arteries, often defined as consistently having systolic blood pressure (the top number in a blood pressure reading) over 130 mmHg and/or diastolic blood pressure (the bottom number) over 80 mmHg. It is also commonly referred to as high blood pressure.

Hypertension can be classified into two types: primary or essential hypertension, which has no identifiable cause and accounts for about 95% of cases, and secondary hypertension, which is caused by underlying medical conditions such as kidney disease, hormonal disorders, or use of certain medications.

If left untreated, hypertension can lead to serious health complications such as heart attack, stroke, heart failure, and chronic kidney disease. Therefore, it is important for individuals with hypertension to manage their condition through lifestyle modifications (such as healthy diet, regular exercise, stress management) and medication if necessary, under the guidance of a healthcare professional.

Genetic polymorphism refers to the occurrence of multiple forms (called alleles) of a particular gene within a population. These variations in the DNA sequence do not generally affect the function or survival of the organism, but they can contribute to differences in traits among individuals. Genetic polymorphisms can be caused by single nucleotide changes (SNPs), insertions or deletions of DNA segments, or other types of genetic rearrangements. They are important for understanding genetic diversity and evolution, as well as for identifying genetic factors that may contribute to disease susceptibility in humans.

Corticosterone is a hormone produced by the adrenal gland in many animals, including humans. It is a type of glucocorticoid steroid hormone that plays an important role in the body's response to stress, immune function, metabolism, and regulation of inflammation. Corticosterone helps to regulate the balance of sodium and potassium in the body and also plays a role in the development and functioning of the nervous system. It is the primary glucocorticoid hormone in rodents, while cortisol is the primary glucocorticoid hormone in humans and other primates.

Nuclear Receptor Subfamily 4, Group A, Member 2 (NR4A2) is a gene that encodes for a protein called Nurr1, which belongs to the nuclear receptor superfamily. These are transcription factors that regulate gene expression by binding to specific DNA sequences. Nurr1 plays crucial roles in the development and function of dopaminergic neurons, which are critical for movement control and are affected in neurodegenerative disorders such as Parkinson's disease. Additionally, Nurr1 has been implicated in various biological processes, including inflammation, immunity, and cancer.

Angiotensinogen is a protein that is produced mainly by the liver. It is the precursor to angiotensin I, which is a molecule that begins the process of constriction (narrowing) of blood vessels, leading to an increase in blood pressure. When angiotensinogen comes into contact with an enzyme called renin, it is cleaved into angiotensin I. Angiotensin-converting enzyme (ACE) then converts angiotensin I into angiotensin II, which is a potent vasoconstrictor and a key player in the body's regulation of blood pressure and fluid balance.

Angiotensinogen is an important component of the renin-angiotensin-aldosterone system (RAAS), which helps to regulate blood pressure and fluid balance by controlling the volume and flow of fluids in the body. Disorders of the RAAS can lead to high blood pressure, kidney disease, and other health problems.

Adrenocorticotropic Hormone (ACTH) is a hormone produced and released by the anterior pituitary gland, a small endocrine gland located at the base of the brain. ACTH plays a crucial role in the regulation of the body's stress response and has significant effects on various physiological processes.

The primary function of ACTH is to stimulate the adrenal glands, which are triangular-shaped glands situated on top of the kidneys. The adrenal glands consist of two parts: the outer cortex and the inner medulla. ACTH specifically targets the adrenal cortex, where it binds to specific receptors and initiates a series of biochemical reactions leading to the production and release of steroid hormones, primarily cortisol (a glucocorticoid) and aldosterone (a mineralocorticoid).

Cortisol is involved in various metabolic processes, such as regulating blood sugar levels, modulating the immune response, and helping the body respond to stress. Aldosterone plays a vital role in maintaining electrolyte and fluid balance by promoting sodium reabsorption and potassium excretion in the kidneys.

ACTH release is controlled by the hypothalamus, another part of the brain, which produces corticotropin-releasing hormone (CRH). CRH stimulates the anterior pituitary gland to secrete ACTH, which in turn triggers cortisol production in the adrenal glands. This complex feedback system helps maintain homeostasis and ensures that appropriate amounts of cortisol are released in response to various physiological and psychological stressors.

Disorders related to ACTH can lead to hormonal imbalances, resulting in conditions such as Cushing's syndrome (excessive cortisol production) or Addison's disease (insufficient cortisol production). Proper diagnosis and management of these disorders typically involve assessing the function of the hypothalamic-pituitary-adrenal axis and addressing any underlying issues affecting ACTH secretion.

Hydrocortisone is a synthetic glucocorticoid, which is a class of steroid hormones. It is identical to the naturally occurring cortisol, a hormone produced by the adrenal gland that helps regulate metabolism and helps your body respond to stress. Hydrocortisone has anti-inflammatory effects and is used to treat various inflammatory conditions such as allergies, skin disorders, and autoimmune diseases. It works by suppressing the immune system's response to reduce swelling, redness, itching, and other symptoms caused by inflammation.

Hydrocortisone is available in different forms, including oral tablets, topical creams, lotions, gels, and ointments, as well as injectable solutions. The specific use and dosage depend on the condition being treated and the individual patient's medical history and current health status.

As with any medication, hydrocortisone can have side effects, especially when used in high doses or for extended periods. Common side effects include increased appetite, weight gain, mood changes, insomnia, and skin thinning. Long-term use of hydrocortisone may also increase the risk of developing osteoporosis, diabetes, cataracts, and other health problems. Therefore, it is essential to follow your healthcare provider's instructions carefully when using this medication.

Blood pressure is the force exerted by circulating blood on the walls of the blood vessels. It is measured in millimeters of mercury (mmHg) and is given as two figures:

1. Systolic pressure: This is the pressure when the heart pushes blood out into the arteries.
2. Diastolic pressure: This is the pressure when the heart rests between beats, allowing it to fill with blood.

Normal blood pressure for adults is typically around 120/80 mmHg, although this can vary slightly depending on age, sex, and other factors. High blood pressure (hypertension) is generally considered to be a reading of 130/80 mmHg or higher, while low blood pressure (hypotension) is usually defined as a reading below 90/60 mmHg. It's important to note that blood pressure can fluctuate throughout the day and may be affected by factors such as stress, physical activity, and medication use.

Genotype, in genetics, refers to the complete heritable genetic makeup of an individual organism, including all of its genes. It is the set of instructions contained in an organism's DNA for the development and function of that organism. The genotype is the basis for an individual's inherited traits, and it can be contrasted with an individual's phenotype, which refers to the observable physical or biochemical characteristics of an organism that result from the expression of its genes in combination with environmental influences.

It is important to note that an individual's genotype is not necessarily identical to their genetic sequence. Some genes have multiple forms called alleles, and an individual may inherit different alleles for a given gene from each parent. The combination of alleles that an individual inherits for a particular gene is known as their genotype for that gene.

Understanding an individual's genotype can provide important information about their susceptibility to certain diseases, their response to drugs and other treatments, and their risk of passing on inherited genetic disorders to their offspring.

The Cytochrome P-450 (CYP450) enzyme system is a group of enzymes found primarily in the liver, but also in other organs such as the intestines, lungs, and skin. These enzymes play a crucial role in the metabolism and biotransformation of various substances, including drugs, environmental toxins, and endogenous compounds like hormones and fatty acids.

The name "Cytochrome P-450" refers to the unique property of these enzymes to bind to carbon monoxide (CO) and form a complex that absorbs light at a wavelength of 450 nm, which can be detected spectrophotometrically.

The CYP450 enzyme system is involved in Phase I metabolism of xenobiotics, where it catalyzes oxidation reactions such as hydroxylation, dealkylation, and epoxidation. These reactions introduce functional groups into the substrate molecule, which can then undergo further modifications by other enzymes during Phase II metabolism.

There are several families and subfamilies of CYP450 enzymes, each with distinct substrate specificities and functions. Some of the most important CYP450 enzymes include:

1. CYP3A4: This is the most abundant CYP450 enzyme in the human liver and is involved in the metabolism of approximately 50% of all drugs. It also metabolizes various endogenous compounds like steroids, bile acids, and vitamin D.
2. CYP2D6: This enzyme is responsible for the metabolism of many psychotropic drugs, including antidepressants, antipsychotics, and beta-blockers. It also metabolizes some endogenous compounds like dopamine and serotonin.
3. CYP2C9: This enzyme plays a significant role in the metabolism of warfarin, phenytoin, and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. CYP2C19: This enzyme is involved in the metabolism of proton pump inhibitors, antidepressants, and clopidogrel.
5. CYP2E1: This enzyme metabolizes various xenobiotics like alcohol, acetaminophen, and carbon tetrachloride, as well as some endogenous compounds like fatty acids and prostaglandins.

Genetic polymorphisms in CYP450 enzymes can significantly affect drug metabolism and response, leading to interindividual variability in drug efficacy and toxicity. Understanding the role of CYP450 enzymes in drug metabolism is crucial for optimizing pharmacotherapy and minimizing adverse effects.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Aldosterone is synthesized by following the metabolism of progesterone. In the potential case where aldosterone synthase is not ... Deficient aldosterone synthase activity results in impaired biosynthesis of aldosterone while corticosterone in the zona ... Aldosterone synthase converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone ... aldosterone synthase (encoded by CYP11B2 gene) catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that ...
Aldosterone 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 ...
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): ...
"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 ...
... serves as an intermediate in the synthesis of aldosterone by the enzyme aldosterone synthase in the ... 18-Hydroxycortisol Aldosterone synthase Reddish MJ, Guengerich FP (August 2019). "Human cytochrome P450 11B2 produces ... aldosterone by a processive mechanism due to the lactol form of the intermediate 18-hydroxycorticosterone". The Journal of ...
... by the aldosterone synthase enzyme (CYP11B2). Along with its epimer 11α-hydroxyprogesterone (11α-OHP), 11β-OHP has been ... and aldosterone synthase (CYP11B2) that convert progesterone to 11β-OHP.[verification needed] That's why in 21-hydroxylase ... "Structural insights into aldosterone synthase substrate specificity and targeted inhibition". Molecular Endocrinology. 27 (2): ... In the normal route to aldosterone and cortisol, progesterone and 17α-hydroxyprogesterone are first hydroxylated at position 21 ...
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... Aldosterone synthase is normally absent in other sections of the adrenal gland. Aldosterone synthesis is stimulated by several ... 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 ...
2002). "Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase". Endocrinology. 143 (9): 3651- ... Komeima K, Hayashi Y, Naito Y, Watanabe Y (2000). "Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin- ... 1999). "Regulation of neuronal nitric-oxide synthase by calmodulin kinases". J. Biol. Chem. 274 (29): 20597-602. doi:10.1074/ ... "Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/ ...
... is converted to aldosterone by aldosterone synthase, found only in the mitochondria of glomerulosa cells. ... Steroidogenesis Deoxycorticosterone Aldosterone 11-Deoxycortisol 11-Deoxycorticosterone Cortisol R.A. Hill; H.L.J. Makin; D.N. ... Corticosterone is the precursor molecule to the mineralocorticoid aldosterone, one of the major homeostatic modulators of ... potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from pregnenolone to aldosterone. ...
The CYP11B2 gene provides instructions for making another enzyme called aldosterone synthase, which helps produce aldosterone. ... too much aldosterone synthase is produced. This overproduction causes the adrenal glands to make excess aldosterone, which ... produce too much of the hormone aldosterone. Excess aldosterone causes the kidneys to retain more salt than normal, which in ... The abnormal ion flow results in the activation of biochemical processes (pathways) that lead to increased aldosterone ...
... by the action of the enzyme aldosterone synthase. Aldosterone plays an important role in the long-term regulation of blood ... "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant". Biochem ... In the kidneys, aldosterone acts on the distal convoluted tubules and the collecting ducts by increasing the reabsorption of ... Aldosterone is responsible for the reabsorption of about 2% of filtered glomerular filtrate. Sodium retention is also a ...
The enzyme aldosterone synthase (also known as CYP11B2) acts in this location The expression of neuron-specific proteins in the ... Zhou, M.Y.; Gomez-Sanchez, C.E. (1993). "Cloning and Expression of a Rat Cytochrome P-450 11β-Hydroxylase/Aldosterone Synthase ... the 2 major regulators of aldosterone production. Aldosterone regulates the body's concentration of electrolytes, primarily ... Ye, P.; Mariniello, B.; Mantero, F.; Shibata, H.; Rainey, W. E (2007). "G-protein-coupled receptors in aldosterone-producing ...
... but aldosterone synthase is also able to perform an 18-oxidation. Moreover, aldosterone synthase is found within the zona ... The last part is mediated either by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). ... and aldosterone (C 21H 28O 5). (Note that cortisone and aldosterone are isomers.) The main corticosteroids produced by the ... Mineralocorticoids such as aldosterone are primarily involved in the regulation of electrolyte and water balance by modulating ...
"Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, ... molecular dynamics simulation studies also indicate that ethyl caffeate is a potential inhibitor of the aldosterone synthase ( ... CYP11B2), a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure ...
It specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β- ... Aldosterone synthase inhibitors, Antiglucocorticoids, Fluoroarenes, Imidazoles, Nitriles, Novartis brands, Orphan drugs, ...
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 ...
Aldosterone synthase (CYP11B2) inhibitors such as metyrapone, mitotane, and osilodrostat prevent the production of the potent ... Farnesyl pyrophosphate synthase (FPPS) inhibitors prevent the conversion of isopentenyl pyrophosphate (IPP) into farnesyl ... Jürg Müller (6 December 2012). Regulation of Aldosterone Biosynthesis. Springer Science & Business Media. pp. 39-. ISBN 978-3- ... and aldosterone from the less potent corticosteroids 11-deoxycorticosterone and 11-deoxycortisol and are used in the diagnosis ...
... and Aldosterone synthase (CYP11B2). CYP11 can be divided into A to E five subfamilies, and CYP11A are the ohonologues to CYP11C ...
Hyperaldosteronism Pseudohyperaldosteronism Glucocorticoid-remediable aldosteronism Aldosterone and aldosterone synthase Maria ... In serum both aldosterone and renin levels are low. This disorder presents similarly to hyperaldosteronism, leading to feedback ... The inactivating mutation leads to elevated local concentrations of cortisol in the aldosterone sensitive tissues like the ... leading to aldosterone-like effects in the kidney. This is what causes the hypokalemia, hypertension, and hypernatremia ...
Aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex. Aldosterone synthase ... The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone).[ ... It selectively stimulates secretion of aldosterone. The secretion of aldosterone has a diurnal rhythm. Control of aldosterone ... ACTH increases the activity of existing aldosterone synthase, resulting in an abnormally high rate of aldosterone synthesis and ...
It may be increased in 17α-hydroxylase (CYP17A1) deficiency, in aldosterone synthase (CYP11B2) deficiency, in primary ... reference data for neonates and infants and its application in aldosterone-synthase deficiency". Journal of Chromatography. B, ...
Corticosterone is then converted to aldosterone by aldosterone synthase. Most of the DOC is secreted by the zona fasciculata of ... DOC has about 1/20 of the sodium retaining power of aldosterone, and is said to be as little as one per cent of aldosterone at ... DOC is a precursor molecule for the production of aldosterone. The major pathway for aldosterone production is in the adrenal ... Since DOC has about 1/5 the potassium excreting power of aldosterone, it probably must have aldosterone's help if the serum ...
The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largely ... The synthesis and secretion of aldosterone are mainly regulated by the renin-angiotensin-aldosterone system. ... is produced in the adrenocortical zona glomerulosa by the action of the enzyme aldosterone synthase (also known as CYP11B2). ... "Cloning and expression of a rat cytochrome P-450 11 beta-hydroxylase/aldosterone synthase (CYP11B2) cDNA variant". Biochem. ...
... downregulating aldosterone synthase, CYP11B1, and the production of adrenal steroids (i.e. aldosterone and cortisol). The first ...
Aldosterone synthase 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 ...
... 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 ...
... aldosterone synthase MeSH D12.776.422.220.453.915.099 - aromatase MeSH D12.776.422.220.453.915.200 - cholesterol 7 alpha- ... aldosterone MeSH D12.776.827.275.700.500 - tacrolimus binding protein 1a MeSH D12.776.828.075.350.275 - filgrastim MeSH D12.776 ...
... the Gene mutated will result in an aldosterone synthase that is ACTH-sensitive, which is normally not. GRA appears to be the ... Compare these effects to those seen in Conn's disease, an adrenocortical tumor which causes excess release of aldosterone, that ... Ziaja J, Cholewa K, Mazurek U, Cierpka L (2008). "[Molecular basics of aldosterone and cortisol synthesis in normal adrenals ... DOC has blood-pressure raising effects similar to aldosterone, and abnormally high levels result in hypokalemic hypertension. ...
... aldosterone synthase) - mineralocorticoid synthesis 21-Hydroxylase - corticosteroid synthesis Cytochrome P450 (CYP1, 2, 3) - ...
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 ...
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 ...
Inherited defects in aldosterone biosynthesis thus cause hypovolemia, hyponatremia and hyperkalemia. Defective aldosterone ... Aldosterones main actions are to regulate intravascular volume and serum electrolytes by controlling sodium absorbtion and ... Aldosterone synthase deficiency and related disorders Perrin C White. Mol Cell Endocrinol. 2004. . ... Disorders of the aldosterone synthase and steroid 11beta-hydroxylase deficiencies. Peter M, Dubuis JM, Sippell WG. Peter M, et ...
Steroid 11-β/18-hydrolase; aldosterone synthase; cytochrome P450, subfamily XIB (steroid 11-β-hydrolase), polypeptide 2; ... Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase). Prostaglandin G/H synthase and ... NOS type II; nitric oxide synthase, macrophage. HEP-NOS; INOS; NOS2 NOS3 7q36. Nitric oxide synthase 3 (endothelial cell). ... GSH synthetase; glutathione synthase. GSHS; MGC14098 GSTA1 6p12.1. Glutathione S-transferase A1. GST, class α, 1; GST-ε; H-A; S ...
Aldosterone synthase deficiency. * Allgrove (AAA) Syndrome. * Bilateral adrenal hemorrhage. * C-17 Hydroxylase Deficiency ...
Innovation of novel anti-hypertensive drug(S) that inhibit adrenal aldosterone synthase gene (cyp11b2) expression. In: Folia ... Sugawara, A. (2020). Innovation of novel anti-hypertensive drug(S) that inhibit adrenal aldosterone synthase gene (cyp11b2) ... Innovation of novel anti-hypertensive drug(S) that inhibit adrenal aldosterone synthase gene (cyp11b2) expression. / Sugawara, ... Dive into the research topics of Innovation of novel anti-hypertensive drug(S) that inhibit adrenal aldosterone synthase gene ...
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 ( ...
Aldosterone synthase deficiency type I and II, congenital Hypoaldosteronism (Aldosterone synthase deficiency types I and II, ... Genetic Testing - Corticosterone metiloxidasa types I and II, deficiency ... (See Aldosterone synthase types I and II, ...
Involvement Of Vascular Aldosterone Synthase In Phosphate-Induced Osteogenic Transformation Of Vascular Smooth Muscle Cells. ... Our findings suggest that VSMCs express aldosterone synthase, which is up-regulated by phosphate-induced disruption of APEX1- ... Our findings suggest that VSMCs express aldosterone synthase, which is up-regulated by phosphate-induced disruption of APEX1- ... Involvement Of Vascular Aldosterone Synthase In Phosphate-Induced Osteogenic Transformation Of Vascular Smooth Muscle Cells}, ...
... also known as aldosterone synthase deficiency, is a disorder of excessive amounts of sodium in the urine along with not enough ... Aldosterone synthase helps produce a hormone called aldosterone. Aldosterone regulates blood pressure by maintaining proper ... This gene provides instructions for making an enzyme called aldosterone synthase. The aldosterone synthase enzyme is found in ... The aldosterone synthase enzyme is involved in a series of three chemical reactions that produce aldosterone from other ( ...
However, aldosterone synthase (CYP11B2) is only expressed in the zona granulosa of adrenal glands.1,2 The most common cause of ... Two forms of aldosterone synthase deficiency are described--CMO deficiency types I and II. Clinical features of patients with ... Patients with aldosterone synthase deficiency who present after infancy usually have anorexia, mild dehydration, and abnormal ... The clinical presentation of aldosterone synthase deficiency and the severity of presentation vary with age. Newborns (within ...
... of the adrenal gland and is a precursor for the synthesis of cortisol and aldosterone (see the image below).{file14055}The ... CAH due to aldosterone synthase (CYP11B2) causes a decrease in aldosterone level without affecting cortisol levels. ... In the ZG, under the effect of aldosterone synthase (CYP11B2), DOC is converted to aldosterone through a process including ... Table 2. Relative Blood Levels, Production Rates, and Bioactivity of DOC, Aldosterone, and Cortisol (Open Table in a new window ...
... aldosterone receptor antagonists; and aldosterone synthase inhibitors; ... glycogen synthase kinase-3) inhibitors such as SB-517955, SB-4195052, SB-216763, NN-57-05441 and NN-57-05445; RXR ligands such ... squalene synthase inhibitors; FXR (farnesoid X receptor) and LXR (liver X receptor) ligands; cholestyramine; fibrates; ...
AstraZeneca gains rights to novel aldosterone synthase inhibitor AstraZeneca has entered into an agreement to acquire CinCor ...
Polymorphysms of the aldosterone synthase gene in essential hypertension. A genetic and pharmacogenetic approach in ...
Fiebeler A, Nussberger J, Shagdarsuren E, et al.: Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ ...
Differential regulation of 11 beta-hydroxylase and aldosterone synthase in human adrenocortical H295R cells.. Denner K; Rainey ... Mechanisms of angiotensin II-mediated regulation of aldosterone synthase expression in H295R human adrenocortical and rat ... 3. Aldosterone breakthrough caused by chronic blockage of angiotensin II type 1 receptors in human adrenocortical cells: ... 5. An in vivo role of bone morphogenetic protein-6 in aldosterone production by rat adrenal gland.. Matsumoto Y; Otsuka F; ...
Development of [18F]AldoView as the first highly selective aldosterone synthase PET tracer for imaging of patients with Primary ... Background: Inappropriately high aldosterone in patients with primary hyperaldosteronism (PHA) is due to increased aldosterone ... Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, ... Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or ...
The aldosterone synthase inhibitor FAD286 is suitable for lowering aldosterone levels in ZDF rats but not in db/db mice. Horm. ... Impact of aldosterone synthase inhibitor FAD286 on steroid hormone profile in human adrenocortical cells. Horm. Metab. Res. 49( ... Impact of aldosterone synthase inhibitor FAD286 on steroid hormone profile in human adrenocortical cells. 96th Annual Meeting ... Aldosterone synthase inhibition improves glucose tolerance in Zucker Diabetic Fatty (ZDF) rats. Endocrinology 157:3844-3855. ...
MacKenzie, S. M., Davies, E., Alvarez-Madrazo, S. (2017) Analysis of the aldosterone synthase (CYP11B2) and 11β-hydroxylase ( ... MacKenzie, S. M., Nguyen Dinh Cat, A., van Kralingen, J., Davies, E. (2019) Aldosterone Springer ... MacKenzie, S. M., Van Kralingen, J. C., Davies, E. (2019) Regulation of aldosterone secretion Elsevier ... the aldosterone-mineralocorticoid receptor-Nox1 Axis Life Sciences, 179, pp. 110-119. (doi: 10.1016/j.lfs.2017.05.002) ...
... and that the aldosterone synthase gene is expressed in cardiac tissue (38). Furthermore, it has been reported that aldosterone ... Expression of aldosterone synthase gene in failing human heart: quantitative analysis using modified real-time polymerase chain ... Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. J Card Fail. 1996;2:47-54. ... Aldosterone induces angiotensin-converting-enzyme gene expression in cultured neonatal rat cardiocytes. Circulation. 2001;104: ...
11β = 11β-hydroxylase (P-450c11); 17α = 17α-hydroxylase (P-450c17); 17,20 = 17,20 lyase (P-450c17); 18 = aldosterone synthase ( ... aldosterone, or both. In the most common forms, accumulated hormone precursors... прочитати більше . Conversion of 11- ...
ALDOSTERONE SYNTHASE GENE ?-344? POLYMORPHISM AS A RISK FACTOR OF EARLY LEFT VENTRICULAR REMODELING IN YOUNG HYPERTENSIVE ...
... aldosterone synthase) and CYP11B1 (steroid-11beta-hydroxylase) inhibitors. J Steroid Biochem Mol Biol 96:259-27015985365. ... Ohlsson Å, Cedergreen N, Oskarsson A and Ullerås E (2010) Mixture effects of imidazole fungicides on cortisol and aldosterone ... Secretion of cortisol and aldosterone as a vulnerable target for adrenal endocrine disruption-screening of 30 selected ...
Mutations and overexpression of P450 11B2 (also known as aldosterone synthase) can lead to hypertension, congestive heart ... MeSH Terms: 18-Hydroxycorticosterone/chemistry; 18-Hydroxycorticosterone/metabolism*; Aldosterone/biosynthesis*; Aldosterone/ ... Title: Human cytochrome P450 11B2 produces aldosterone by a processive mechanism due to the lactol form of the intermediate 18- ... P450 11B2 catalyzes aldosterone formation from 11-deoxycorticosterone through three distinct oxidation steps. It is currently ...
... with the coding regions of the aldosterone synthase gene (CYP11B2) on chromosome 8q (7, 8). As a result of this chimeric gene, ... the mineralocorticoid receptor loses its specificity for aldosterone and is activated by both aldosterone and progesterone. ... As a result, aldosterone production is suppressed (18).. Characteristic features of type IV CAH are precocious puberty, ... The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code. J Biol Chem (2005) 280:24824 ...
The selective aldosterone synthase inhibitor Baxdrostat significantly lowers blood pressure in patients with resistant ... Eplerenone: a selective aldosterone receptor antagonist for patients with heart failure. Barnes BJ, Howard PA. Barnes BJ, et al ... Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure. Moore TD, Nawarskas JJ, Anderson JR ... Due to the selectivity of eplerenone for the aldosterone receptor, severe adverse effects such as gynecomastia and vaginal ...
It clinical-stage product candidate is lorundrostat, a proprietary, orally administered, highly selective aldosterone synthase ...
Aldosterone Synthase. CHOLESTEROL 7 ALPHA-MONOOXYGENASE. Cholesterol 7-alpha-Hydroxylase. CHOLESTEROL MONOOXYGENASE (SIDE-CHAIN ...
... gene regulation of aldosterone synthase, and 5) epigenetics of hypertension and diabetes mellitus. ...
The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients. Clinical ...

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