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

Human adrenocortical tissue obtained, on eight occasions, at the time of nephrectomy for renal carcinoma (outside the adrenal pole) was treated by collagenase to dissociate the cells. These were hen submitted to a short, 2-h, incubation with the N-terminal fragment (16 K) of POMC, its derivative, gamma 3-MSH, beta-lipotropin and beta-endorphin, in parallel with ACTH 1-24 (Synacthen Ciba) and angiotensin II (AII, Hypertensin Ciba). Under the influence of ACTH (10(-10) M), and AII (10(-10) M), basal glucocorticoid output, including more than 80% cortisol, was increased by factors of 3 +/- 0.51 (SEM) and 1.35 +/- 0.12 (SEM), respectively. The corresponding aldosterone responses were 1.60 +/- 0.13 for ACTH and 1.38 +/- 0.09 for AII. With the exception of gamma 3-MSH, the POMC peptides under study had no steroidogenic effect. gamma 3-MSH (10(-9) M) and AII (10(-10) M) stimulated aldosterone production to approximately similar levels of, respectively, 1.23 +/- 0.05 and 1.38 +/- 0.09 times the basal production. In contrast to AII however, gamma 3-MSH showed no apparent effect on glucocorticoid output. Steroidogenic response to ACTH was potentiated by gamma 3-MSH at a concentration of 10(-10) M which, when used alone, proved ineffective. This potentiating effect was pronounced for the aldosterone response, whereas the glucocorticoid production was hardly affected. This action ceased to be visible when the cells reached maximal stimulation by ACTH. These findings suggest that gamma 3-MSH--a portion of the 16 K fragment--may have a possible role in aldosterone secretion.
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PMID:Compared effects of ACTH, angiotensin II and POMC peptides on isolated human adrenal cells. 300 85

1. In familial hyperaldosteronism type I (FH-I), expression of an adrenocorticotropic hormone (ACTH)-dependent hybrid 11 beta-hydroxylase/aldosterone synthase gene causes excessive 'hybrid steroid' (18-hydroxy- and 18-oxo-cortisol) production. In order to study the mechanism of elevated 'hybrid steroid' levels in angiotensin-unresponsive (AII-U) aldosterone-producing adenoma (APA), we compared responses of 24 h urinary 18-oxo-cortisol, aldosterone and cortisol to dexamethasone (0.5 mg q6h for 4 days) in 11 FH-I patients, 11 patients with AII-U APA, 11 patients with AII-responsive (AII-R) APA and 10 patients with bilateral adrenal hyperplasia (BAH). 2. Consistent, marked suppression (by at least 60%) of 18-oxo-cortisol levels by dexamethasone was seen in all groups except AII-U APA. Aldosterone levels were consistently suppressed to undetectable levels only in FH-I. Cortisol levels were suppressed to undetectable levels in all patients except two with AII-U APA. 3. Production of both 18-oxo-cortisol and aldosterone (and occasionally cortisol) in AII-U APA appears relatively ACTH-independent, consistent with a common mechanism involved in the formation of these two steroids from their respective precursors, which differs from that in FH-I. 4. In AII-R APA and BAH, 18-oxo-cortisol production appears markedly ACTH-dependent, but aldosterone production is not.
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PMID:Production of 18-oxo-cortisol in subtypes of primary aldosteronism. 880 May 94