Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells isolated from five aldosterone-producing adenomas were used to study glucocorticoid and aldosterone production in response to ACTH, angiotensin II (A II), and peptides derived from proopiomelanocortin (POMC), viz. the 16K N-terminal fragment (16K) and its derivative, gamma 3MSH and the C-terminal fragment beta-lipotropin (beta LPH) and its derivative beta-endorphin. At concentrations similar to those of ACTH and A II (10(-12)-10(-10) M), 16K, gamma 3MSH, and beta LPH selectively stimulated aldosterone production, which reached levels close to those obtained with A II. ACTH, however, was the most effective stimulant of steroidogenesis. The 16K, gamma 3MSH, and beta LPH peptides potentiated the action of ACTH, particularly in the case of aldosterone production. beta-Endorphin, whether used alone or in association with ACTH, had no effect on steroidogenesis at the dose used (10(-10) M). The principal glucocorticoid products of the adenoma cells were cortisol and corticosterone. The ratios of corticosterone to cortisol (B/F) and aldosterone to corticosterone (A/B) varied considerably from one adenoma to another, both basally and in response to ACTH. Nevertheless, within individual adenomas, the mean B/F ratio induced by ACTH [0.280 +/- 0.013 (+/- SEM)] was significantly larger than that induced by A II (0.127 +/- 0.007; P less than 0.001). By contrast, the A/B ratio in response to ACTH (0.061 +/- 0.003) was significantly smaller than that in response to A II (0.159 +/- 0.010; P less than 0.001). The values obtained with 16K (B/F, 0.106 +/- 0.010; A/B, 0.192 +/- 0.028) and gamma 3MSH (B/F, 0.122 +/- 0.012; A/B, 0.178 +/- 0.020) were close to those obtained with A II. 16K and gamma 3MSH potentiated ACTH's effect on steroidogenesis mainly by increasing the A/B ratio from 0.061 +/- 0.003 for ACTH alone to 0.100 +/- 0.008 for 16K plus ACTH (P less than 0.005) and to 0.092 +/- 0.005 for gamma 3MSH plus ACTH (P less than 0.001). The findings suggest that the stimulation of aldosterone production by 16K and gamma 3MSH in aldosteronoma cells is of the A II type and that these peptides may play a role in the genesis of primary aldosteronism.
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PMID:Effects of proopiomelanocortin peptides and angiotensin II on steroidogenesis in isolated aldosteronoma cells. 299 20

Basal and modulated secretion of ACTH and lipotropin (LPH) by cultures of trypsin-dispersed cells of a biopsy of a human corticotropic adenoma have been examined. ACTH secretion was detectable throughout the period of culture (13 days) but declined steadily from an initial production rate of 238 +/- 124 ng/3 X 10(5) cells/12 h. The time course of secretion showed a slower phase over the first 4 h, with increases up to 12 h. An extract of rat stalk median eminence caused a significant (P less than 0.005) dose-dependent increase in both ACTH and LPH secretion during 30 min. The patterns of response for ACTH and LPH were very similar; both exhibited a decline in the basal release of peptide subsequent to the period of stimulation. The addition of hydrocortisone (0.2 micrograms/ml) did not suppress basal ACTH secretion during 30 min but significantly (P less than 0.05) inhibited stimulation produced by rat stalk median eminence extract. Arginine vasopressin (dose range, 1-9 ng/ml) significantly (P less than 0.025) stimulated both ACTH and LPH secretion during 30 min. The patterns of response were again very similar. Serotonin (dose range, 0.01-10 micrograms/ml) did not affect ACTH secretion during incubations of 30 min to 4 h. The results obtained with the cell cultures of a human corticotropic cell adenoma concur with in vivo findings of incomplete autonomy of secretion, parallel secretion of ACTH and LPH in response to provocative stimuli, and suppression by corticosteroids. The technique has potential for exploring the cellular mechanisms controlling secretion by human corticotropic adenomas as well as the nature of the hormones produced.
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PMID:Adrenocorticotropin and lipotropin secretion by dispersed cell cultures of a human corticotropic adenoma: effect of hypothalamic extract, arginine vasopressin, hydrocortisone, and serotonin. 625 Nov 5

Using RIAs for six regions within proopiolipomelanocortin (proOLMC), gel filtration, and electrophoresis, we studied pituitary peptides in a normal horse and one with Cushing's disease caused by a pars intermedia adenoma. Almost all immunoreactive (IR) ACTH (78%) was 4,500 mol wt (4.5K) ACTH in normal pars distalis, but it was almost 100% corticotropin-like intermediate lobe peptide (CLIP) in normal pars intermedia. alpha MSH and beta MSH were found mainly in pars intermedia: equal concentrations of the beta MSH precursors, beta-lipotropin (beta LPH) and gamma LPH, were found in pars distalis. Most IR-beta-endorphin (IR-beta END) was found as beta END in pars intermedia, but roughly equal concentrations of beta END and its precursor, beta LPH, were found in pars distalis. A 33K molecule containing IR-ACTH, IR-gamma 3MSH, and IR-beta END, presumed to be proOLMC, and a variety of 15-27K presumed biosynthetic intermediates were found in both normal pars distalis and pars intermedia. The pars intermedia adenoma causing Cushing's syndrome contained high IR-peptide concentrations. Several differences in precursors were noted, including the presence of three larger presumed precursors (38.5K, 47K, and 63K) that had both ACTH and beta END immunoreactivities and both deletions and additions of 15-27K intermediates. The Cushing's horse's plasma peptides reflected tumor concentrations; 4.5K ACTH was modestly elevated, but the concentrations of CLIP, alpha MSH, beta MSH, gamma LPH, and beta END were dramatically increased. About 20% of plasma IR-ACTH and 5% of IR-beta MSH and IR-beta END were found as high molecular weight forms. Normal processing of horse proOLMC appears to be similar to that in other species, but may be altered in pars intermedia tumors of horses with Cushing's disease, the plasma of which contains disproportionately increased concentrations of pars intermedia proOLMC peptides.
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PMID:Proopiolipomelanocortin peptides in normal pituitary, pituitary tumor, and plasma of normal and Cushing's horses. 627 64

ACTH and lipotropins (beta- and gamma-LPH) are synthesized from a common precursor by the pituitary corticotropic cell. We have measured LPH plasma levels under physiological and pathological conditions and we have compared them with ACTH plasma levels in the same circumstances. Spontaneous variations (nycthemeral rhythm) in LPH, ACTH and cortisol plasma levels were parallel, while responses to Dexamethasone freination test and stress (Insulin induced hypoglycemia) or more specific stimulation (Metopirone, lysine-vasopressin) were parallel and superimposable. LPH levels were always higher than ACTH levels in two pathological circumstances: chronic renal failure and Cushing's syndromes with ectopic ACTH producing tumors. The determination of both ACTH and LPH levels assists the diagnosis of corticotropic insufficiency and etiologic investigation of Cushing's syndrome, after hypercorticolism had been established. Although unable to confirm the presence of corticotropic adenoma in patients with Cushing's disease, or the predict effectiveness of pituitary surgery, these determination bring good arguments for treated Cushing's diseases follow up.
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PMID:[ACTH, beta-endorphin and lipotropins: physiopathological studies in man (author's transl)]. 628 91

Dispersed corticotrophic cells of 3 patients with Nelson's syndrome were studied in tissue culture for up to 25 days. During this culture period a parallel decrease with time was seen in ACTH and beta-endorphin-like immunoreactivity ( LIR ) release. A concomitant decline was observed for intracellular hormones. The time course of hormone release showed a parallel secretion of ACTH and beta-endorphin- LIR up to 8 h. Both the release of ACTH and beta-endorphin LIR were stimulated by 0.1 microM lysine vasopressin (LVP) in all three adenoma cell cultures. Dexamethasone (0.1 and 1 microM) suppressed basal hormone secretion for 4 h. Synthetic ovine corticotrophin-releasing factor (CRF) at 10 and 100 nM stimulated the secretion of ACTH and beta-endorphin LIR maximally. This stimulation was higher than observed with maximal stimulative concentration of LVP (0.3 microM). The CRF-mediated hormone secretion was calcium-dependent. Dexamethasone (0.1 microM) blocked the stimulating effect of 10 nM CRF completely. Gel-filtration chromatography demonstrated the cells to secrete both beta-lipotrophin (beta-LPH) and beta-endorphin. The ratio of beta-LPH to beta-endorphin released remained constant upon stimulation by LVP and CRF. HPLC studies demonstrate the possibility that several beta-endorphin fragments, including alpha-endorphin and gamma-endorphin, were secreted by cells from a Nelson tumour. CRF caused a simultaneous parallel stimulation of the release of these peptides.
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PMID:ACTH and beta-endorphin secretion by three corticotrophic adenomas in culture. Effects of culture time, dexamethasone, vasopressin and synthetic corticotrophin releasing factor. 632 19