Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exciting developments in knowledge of primary aldosteronism include description of new subtypes and elucidation of the genetic basis of one variety. Furthermore, relatively simple biochemical screening (aldosterone/renin ratio) has disclosed that primary aldosteronism is more common than previously thought, by diagnosing patients at an earlier, normokalaemic stage. The mutant gene discovered in the glucocorticoid-suppressible variety (FHI) codes for an aldosterone biosynythetic enzyme normally controlled by angiotensin II, and now controlled by corticotropin. The zona fasciculata is hyperplastic and makes aldosterone and "hybrid steroids" 18-oxocortisol and 18-hydroxycortisol in excess, in response to ACTH but not to angiotensin II. Adrenal tumours have not yet been described in this condition. Aldosterone-producing adenomas (Conn's syndrome) are also commonly composed of zona fasciculata-like cells, make "hybrid steroids" in excess and are very sensitive to ACTH but not to angiotensin II. We have described a new variety of aldosterone-producing adenoma which is responsive to angiotensin II (AII-responsive APA), consists of at least 20% zona glomerulosa-like cells, and does not make "hybrid steroids" in excess. We have also described a new familial variety of primary aldosteronism that includes tumours and is not glucocorticoid-suppressible (FHII). We propose that primary aldosteronism is a spectrum of genetic diseases expressed as either hyperplasia or neoplasia, and that morphological and genetic diversity explains biochemical and clinical behaviour.
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PMID:Primary aldosteronism: hypertension with a genetic basis. 135 75

Immunoreactive plasma levels of the proopiolipomelanocortin-derived peptides, ACTH, beta-endorphin-lipotropin, and gamma 3MSH, were measured in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism. Plasma peptide concentrations in patient groups were not different from those in normal controls. Removal of aldosterone-producing adenomas in three patients and of an aldosterone-producing adrenocortical carcinoma in one patient did not affect plasma peptide concentrations. Furthermore, infusion of the opiate antagonist naloxone (0.2 mg/min) in one patient with bilateral adrenal hyperplasia had no effect on either plasma aldosterone or cortisol. These results suggest that the proopiolipomelanocortin-derived peptides are not overproduced in states of hyperaldosteronism.
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PMID:Plasma immunoreactive proopiolipomelanocortin-derived peptides in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism. 630 Jan 69

Cells were isolated from one of two adenomas from the adrenal cortex of a hypertensive patient with primary hyperaldosteronism. A primary culture of these cells responded with increased aldosterone secretion to gamma 3-MSH and human (residues 1-76) and porcine (residues 1-80) N-terminal peptides of pro-opiomelanocortin (POMC). EC50 was lowest for gamma 3-MSH, while maximal response was greater for both N-terminal peptides of POMC. We conclude that gamma 3-MSH derived from the N-terminal segment of POMC contains the active core of the aldosterone-stimulating activity of the N-terminal on these adrenal cells.
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PMID:Response of human aldosteronoma cells in culture to the N-terminal glycopeptide of pro-opiomelanocortin and gamma 3-MSH. 686 54

A novel glycopeptide has been isolated from human and porcine pituitary glands. This substance is the amino-terminal fragment of pro-opiomelanocortin (POMC). The complete amino acid sequence has been determined. When tested for its steroid stimulating activity on an aldosterone secreting human adrenocortical adenoma, it was found to be more potent than angiotensin and ACTH. These results raise the interesting possibility that primary hyperaldosteronism could be related to a pituitary adrenal dysfunction.
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PMID:Primary hyperaldosteronism: a pituitary--adrenal dysfunction related to a new pituitary glycopeptide? 716 Jan 8

Proopiomelanocortin (POMC) is a protein that contains the amino acid sequences of numerous peptide hormones, including the melanocyte-stimulating hormones (MSH). MSH peptides of alpha, beta, and gamma primary structure are present in plasma, and all exhibit natriuretic activity. Intravenous infusion of alpha or beta-MSH leads to a time- and dose-dependent natriuresis, whereas gamma-MSH is reported to be natriuretic at low doses but antinatriuretic at high doses. The natriuretic activity of MSH peptides occurs without change in arterial pressure or renal hemodynamics, suggesting a possible direct tubular inhibition of sodium reabsorption. Intravenously infused gamma-MSH is associated with an increase in the plasma concentration of atrial natriuretic peptide. In addition, gamma-MSH also has a direct intrarenal natriuretic action that is dependent on the renal nerves. In rats, gamma-MSH-related peptides are involved in the reflex control of sodium excretion in situations such as the natriuresis that occurs (a) from the remaining kidney after acute unilateral nephrectomy, (b) from the contralateral kidney shortly after unilateral ureteral pressure elevation, and (c) after unilateral carotid artery traction. POMC-derived peptides (including MSH) are modulated in response to salt loading, and alterations in POMC metabolism and plasma peptide concentrations have been observed in genetically hypertensive rats and during the development of adrenal regeneration hypertension. In addition, plasma gamma-MSH levels are elevated in patients with severe congestive heart failure, and in primary hyperaldosteronism. These observations suggest a possible involvement of MSH-related peptides in sodium homeostasis as well as in certain forms of hypertension.
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PMID:Natriuretic properties of melanocyte-stimulating hormones. 750 15

The cDNA clone pG2 was originally isolated from a human pheochromocytoma. The respective gene was found to be strongly expressed in normal adrenal zona glomerulosa and medulla, as well as in Conn's adenomas and pheochromocytomas. To shed more light on the expression and regulation of the pG2 gene, we investigated its expression in a wide variety of different adrenal neoplasms and cultured adrenal cells. Northern blot analysis was used to determine the steady state level of pG2 mRNA. Besides normal adrenals, Conn's adenomas and pheochromocytomas, we found abundant expression of pG2 mRNA in Cushing's, virilizing and nonfunctional adrenocortical adenomas and carcinomas, as well as in hyperplastic adrenals. The relative levels of pG2 mRNA in various adrenocortical tumors were not significantly different from those in normal adrenals and pheochromocytomas. In primary cultures of normal adrenal cells, treatment with adrenocorticotropin induced a 3- to 15-fold increase in the expression of pG2 mRNA (P<0.01), and this effect was reproduced by incubation with (Bu)2cAMP. In cultured pheochromocytoma cells, treatment with (Bu)2cAMP and a protein kinase inhibitor, staurosporine, increased pG2 mRNA accumulation (2- to 4-fold over the control level, P<0.01, and 3- to 8-fold, P<0.01, respectively). These results indicate that pG2 is widely expressed in normal and pathological adrenal tissues from both cortical and medullary origin, which eliminates its usefulness as a specific marker for zona glomerulosa or medullary adrenal tumors. Accumulation of pG2 mRNA is regulated by multiple differentiating factors through different pathways in primary cultures of normal adrenal and pheochromocytoma cells.
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PMID:pG2 gene expression and its regulation in human adrenocortical and medullary tumors. 1036 15

Primary hyperaldosteronism (PHA), autonomic secretion of aldosterone by the adrenal gland, is rare. PHA usually results in therapy-resistant hypertension and is often but not always accompanied by hypokalaemia. Common causes of PHA are an aldosterone-producing adenoma, idiopathic aldosterone hypersecretion, unilateral hyperplasia or a genetic variant: glucocorticoid-remediable aldosteronism (GRA). The diagnosis should be phased and first of all requires a biochemical confirmation of the presence of PHA. In PHA patients, plasma renin is invariably suppressed. Blood should be collected under standardised conditions while the patient is not using beta-blockers or centrally-acting antihypertensive medication. Patients with a suppressed plasma renin and an elevated plasma aldosterone concentration have PHA. In patients with a suppressed plasma renin and a high-normal plasma aldosterone concentration a confirming test should be performed in which PHA is diagnosed if aldosterone is not suppressed following volume expansion with sodium chloride. The cause of PHA is determined by means of a CT scan or MRI of the adrenal glands to find a unilateral adenoma. If the CT scan or MRI is normal, adrenal vein aldosterone sampling may be considered as a next step in order to demonstrate lateralisation of aldosterone production. The hypertension and hypokalaemia of all forms of PHA respond well to spironolactone therapy. In the case of a unilateral adenoma or unilateral hyperplasia, adrenalectomy is the treatment of choice. For GRA, dexamethasone in doses that reduce the corticotropin (ACTH) level is indicated.
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PMID:[Primary hyperaldosteronism]. 1295 26

Primary aldosteronism, congenital adrenal hyperplasia, Cushing's syndrome, glucocorticoid-remediable aldosteronism, and corticotropin-dependent forms of adrenal pathology can cause hypertension by excessive production of adrenocortical hormones. Although traditional biochemical assays continue to be used, genetic testing has simplified the diagnosis of glucocorticoid-remediable aldosteronism. Also, new interventional radiologic approaches for the diagnosis and treatment of corticotropin-dependent forms of Cushing's syndrome are available. Medical and surgical approaches, however, still remain viable options for treatment.
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PMID:Adrenocortical hypertension. 1648 Jun 76

Primary aldosteronism, congenital adrenal hyperplasia, Cushing's syndrome, glucocorticoid-remediable aldosteronism, and corticotropin-dependent forms of adrenal pathology can cause hypertension by excessive production of adrenocortical hormones. Although traditional biochemical assays continue to be used, genetic testing has simplified the diagnosis of glucocorticoid-remediable aldosteronism. Also new interventional radiologic approaches for the diagnosis and treatment of corticotropin-dependent forms of Cushing's syndrome are available. Medical and surgical approaches, however, still remain viable options for treatment.
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PMID:Adrenocortical hypertension. 1512 76

Glucocorticoid-remediable aldosteronism (GRA) is a hereditary form of primary hyperaldosteronism and the most common monogenic cause of hypertension. A chimeric gene duplication leads to ectopic aldosterone synthase activity in the cortisol-producing zona fasciculata of the adrenal cortex, under the regulation of adrenocorticotropin (ACTH). Hypertension typically develops in childhood, and may be refractory to standard therapies. Hypokalemia is uncommon in the absence of treatment with diuretics. The discovery of the genetic basis of the disorder has permitted the development of accurate diagnostic testing. Glucocorticoid suppression of ACTH is the mainstay of treatment; alternative treatments include mineralocorticoid receptor antagonists.
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PMID:Glucocorticoid-remediable aldosteronism. 2156 70


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