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)

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

The effect of estradiol on the brain concentration of immunoreactive beta-endorphin (beta-EP) and C-terminal ACTH (CLIP) was studied in ovariectomized rats. Dopamine, a known inhibitor of pituitary intermediate lobe pro-opiomelanocortin (POMC), was examined as a possible mediator of the estradiol induced changes in brain POMC. Animals were treated for 1 or 3 weeks with either 1) saline; 2) silastic estradiol implants; or 3) estradiol implants plus haloperidol 1 mg/kg/day. After one week of treatment no significant change in hypothalamic beta-EP content was noted in any group compared to the control level of 4.13 +/- .33 (SEM) pmoles although in the neurointermediate lobe beta-EP increased from 566 +/- 72 to 942 +/- 73 pmoles after haloperidol (p less than .005). After 3 weeks, however, hypothalamic beta-EP decreased from 3.96 +/- .28 to 2.74 +/- .19 pmoles (p less than .005) and C-terminal ACTH decreased from 3.78 +/- .33 to 2.82 +/- .18 pmoles (p less than .02) in the estradiol treated rats. This estradiol induced decrease in the hypothalamic content of beta-EP and C-terminal ACTH was not blocked by haloperidol. We conclude that estradiol lowers the hypothalamic content of beta-EP and CLIP and that this effect does not appear to be mediated by dopamine.
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PMID:Regulation of beta-endorphin and ACTH in brain by estradiol. 299 73

Pituitary-adrenocortical responses to the iv injection of 100 micrograms synthetic ovine corticotropin-releasing hormone (CRH) were studied in 13 patients with anorexia nervosa, and the concentrations of immunoreactive CRH in cerebrospinal fluid were measured in 7 of them. Mean basal levels of plasma ACTH and cortisol were 32 +/- 5 pg/ml (+/- SEM) and 21.1 +/- 1.5 micrograms/dl, respectively. The latter value was significantly higher than that in age-matched normal women (P less than 0.005). The mean increments of plasma ACTH and cortisol in response to CRH injection in those 13 patients were 21 +/- 5 pg/ml and 5.3 +/- 1.7 micrograms/dl, respectively, significantly lower than those in normal women (58 +/- 6 pg/ml and 15.3 +/- 7.7 micrograms/dl, respectively; P less than 0.005). When 4 patients were reexamined after weight gains of between 3 and 22 kg, their responses to the CRH injection increased. The mean concentration of immunoreactive CRH in the cerebrospinal fluid of seven patients was 30.8 +/- 3.9 pg/ml (+/- SEM), which was higher than the value of 18.4 +/- 1.1 pg/ml (P less than 0.005) in control subjects with cervical spondylosis. These findings suggest the possibility that hypersecretion of CRH may occur in patients with anorexia nervosa.
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PMID:The responses of plasma adrenocorticotropin and cortisol to corticotropin-releasing hormone (CRH) and cerebrospinal fluid immunoreactive CRH in anorexia nervosa patients. 300 Nov 25

This study was designed to compare the responsiveness of adrenocorticotropin (ACTH) and cortisol secretion to corticotropin-releasing factor (CRF) in the morning and early evening in normal human subjects. Synthetic ovine CRF (1.0 micrograms/kg) or normal saline, was administered as an i.v. bolus injection to six normal males at 900 h and 1700 h. Blood samples were obtained before and 15, 30, 60, 90 and 120 min after CRF or saline injection. Significant increases in plasma ACTH and cortisol levels were observed in all subjects at the both time of testing after CRF injection. The net increments in the areas under the concentration curve (areas in the CRF experiment minus those in the saline control experiment) were not statistically different for both ACTH (mean +/- SEM: 41.0 +/- 10.6 pg/ml h in the morning: 51.1 +/- 8.9 pg/ml h in the evening) and cortisol (mean +/- SEM: 28.5 +/- 5.0 micrograms/dl h in the morning; 36.2 +/- 4.0 micrograms/dl h in the evening). Also no significant difference was observed in net increment, peak level and the ratio of peak level to the basal level of ACTH and cortisol after CRF injection. There were no appreciable changes in plasma concentrations of growth hormone, thyroid-stimulating hormone or prolactin, although slight but statistically significant rises in plasma levels of luteinizing hormone and follicle-stimulating hormone were observed. These results suggest that there is no significant difference in responsiveness of the pituitary-adrenal axis to CRF in the morning (900 h) and early evening (1700 h), and thus the time of day will not necessarily have to be considered when CRF is used between these times in a clinical test to evaluate pituitary ACTH reserve.
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PMID:Responses of plasma adrenocorticotropin and cortisol to intravenous injection of synthetic ovine corticotropin releasing factor in the morning and early evening in normal human subjects. 300 29

The ACTH and cortisol responses to 100 micrograms ovine corticotropin-releasing hormone (CRH) in 19 consecutive patients with Cushing's disease were compared with those in 13 normal subjects. In 2 patients with Cushing's disease, plasma ACTH and cortisol did not increase after CRH administration. Compared to the normal subjects, maximal ACTH increments [135 +/- 25 (+/- SEM) vs. 42 +/- 6 pg/ml; P less than 0.001, by Wilcoxon's two-sample test] and maximal cortisol increments (17.7 +/- 1.8 vs. 9.4 +/- 1.1 micrograms/100 ml; P less than 0.01 by Wilcoxon's test) after CRH were significantly higher in the 17 CRH-responsive patients with Cushing's disease. In the normal subjects, there was a significant negative correlation between the basal cortisol level and the maximal ACTH (r = -0.65; P less than 0.05, by Spearman's rank correlation test) and cortisol (r = -0.95; P less than 0.001, by Spearman's test) responses to CRH. In contrast, in the CRH-responsive Cushing patients, there was no significant correlation between the basal cortisol level and the maximal ACTH (r = 0.10; P greater than 0.10, by Spearman's test) and cortisol (r = 0.14; P greater than 0.10, by Spearman's test) increments after CRH treatment. In the normal subjects, there was no significant correlation between the basal ACTH level and the maximal ACTH increments after CRH administration (r = -0.24; P greater than 0.10, by Spearman's test). Again in contrast, in the CRH-responsive Cushing patients, maximal ACTH increments after CRH treatment correlated positively with basal ACTH levels (r = 0.69; P less than 0.005, by Spearman's test). Moreover, in these patients, the maximal ACTH increments after CRH were positively correlated with the ACTH levels after suppression with higher and lower doses of dexamethasone. We conclude that in Cushing's disease, unlike in normal subjects, circulating cortisol is not the major modulator of ACTH and cortisol responses to CRH, and that in these patients, responsivity of ACTH to CRH and lack of suppressibility by dexamethasone are related phenomena.
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PMID:Responsivity of adrenocorticotropin to corticotropin-releasing hormone and lack of suppressibility by dexamethasone are related phenomena in Cushing's disease. 300 53

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

The ability of two proopiomelanocortin-derived peptides, alpha MSH and corticotropin-like intermediate lobe peptide (CLIP) [ACTH (18-39)] to antagonize the stimulation of PRL secretion by beta-endorphin (beta EP) was studied in the rat. When 50 ng beta EP were injected into the lateral cerebral ventricle, plasma PRL rose from a mean baseline of 1.87 +/- 0.43 ng/ml (+/- SEM) to a peak of 23.0 +/- 3.67 ng/ml 10 min after the injection. When the same animals received 500 ng alpha MSH together with 50 ng beta EP, the peak concentration of PRL was reduced by 74% to 6.05 +/- 1.43 ng/ml (P less than 0.005). After the injection of 500 ng CLIP together with 500 ng beta EP, the peak concentration of PRL was reduced by 47% to 12.8 +/- 3.09 ng/ml (P less than 0.01). Total PRL release, determined by calculating the areas under the plasma PRL concentration curves, was also significantly reduced by the injection of alpha MSH or CLIP. A dose of 100 ng alpha-MSH or CLIP also antagonized the stimulation of PRL secretion by 50 ng beta EP. PRL release was reduced by 62% after administration of 100 ng alpha MSH (P less than 0.001) and by 43% after 100 ng CLIP (P less than 0.05). When 100 ng alpha MSH and 100 ng CLIP were injected together, there was an additive effect in blocking the stimulation of PRL release by beta EP, and the peak plasma PRL concentration was reduced by 81%. Des-acetyl alpha MSH, the predominant form of alpha MSH in the hypothalamus, was also very effective in antagonizing beta EP-induced PRL release. The peak PRL concentration was reduced by 52% after administration of 100 ng des-acetyl alpha MSH plus 50 ng beta EP compared with that after beta EP alone (P less than 0.005). We conclude that relatively low doses of both alpha MSH and CLIP can effectively antagonize the actions of beta EP on pituitary PRL release. These findings suggest the possibility that differential posttranslational processing of proopiomelanocortin may serve as a regulator of anterior pituitary function.
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PMID:Antagonism of beta-endorphin-induced prolactin release by alpha-melanocyte-stimulating hormone and corticotropin-like intermediate lobe peptide. 301 83

To further elucidate the site of action of opioids on the pituitary-adrenal axis, we studied the effect of D-Ala2,MePhe4,met-(O)enkephalin-ol (Sandoz, FK 33-824) on plasma ACTH and beta-endorphin immunoreactivity and serum cortisol in 7 normal subjects and 11 patients with Cushing's syndrome (Cushing's disease, n = 7; adrenal adenoma, n = 2; ectopic Cushing's syndrome, n = 2) after administration of human corticotropin-releasing hormone (hCRH). hCRH (0.1 mg; Bachem) was injected iv after pretreatment with 0.5 mg FK 33-824, im, or 0.9% saline. In normal subjects, the hCRH-induced ACTH, beta-endorphin, and cortisol increases were almost completely abolished by pretreatment with FK 33-824. Mean peak (+/- SEM) hormone concentrations were significantly reduced (ACTH, 16.7 +/- 3.5 vs. 45.3 +/- 7.8 pg/ml; beta-endorphin, 151 +/- 25 vs. 277 +/- 51 pg/ml; cortisol, 8.1 +/- 1.2 vs. 19.5 +/- 2.6 micrograms/dl; P less than 0.02), as were secretory areas (P less than 0.02). These results indicate a direct pituitary action of the synthetic met-enkephalin. In contrast, in patients with Cushing's disease, FK 33-824 did not inhibit hCRH-induced hormone release. Instead, maximum ACTH and beta-endorphin concentrations were slightly but not significantly higher after the administration of FK 33-824 (ACTH, 292 +/- 143 vs. 131 +/- 32 pg/ml; beta-endorphin, 2409 +/- 763 vs. 1921 +/- 600 pg/ml). These findings indicate a defect in inhibitory opiodergic control of ACTH secretion in patients with Cushing's disease, which may contribute to the pathological ACTH hypersecretion. In patients with Cushing's syndrome due to an adrenal adenoma or ectopic ACTH secretion, neither hCRH nor FK 33-824 altered hormone concentrations.
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PMID:FK 33-824, a met-enkephalin analog, blocks corticotropin-releasing hormone-induced adrenocorticotropin secretion in normal subjects but not in patients with Cushing's disease. 302 23

To assess the effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia, six healthy male volunteers each underwent two insulin tolerance tests in random order, separated by at least 1 week with and without atropine. ACTH levels were significantly greater at +45 min (mean +/- SEM, 223 +/- 21 pg/ml vs 148 +/- 15 pg/ml, P less than 0.01) and at +120 min (54 +/- 11 pg/ml vs 29 +/- 10 pg/ml, P less than 0.05). beta-endorphin levels were significantly greater at +30 min (170 +/- 45 pg/ml vs 96 +/- 32 pg/ml, P less than 0.05) and at +105 min (81 +/- 14 pg/ml vs 54 +/- 7 pg/ml, P less than 0.01). Cholinergic blockade had no effect on plasma glucose or cortisol concentrations. This study demonstrates that cholinergic blockade with atropine facilitates the ACTH and beta-endorphin responses to insulin-induced hypoglycaemia without altering the cortisol responses.
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PMID:The effect of cholinergic blockade on the ACTH, beta-endorphin and cortisol responses to insulin-induced hypoglycaemia. 302 69

To further investigate the role of opioids in the regulation of the pituitary-adrenal axis we studied the effect of morphine and naloxone on human corticotropin-releasing hormone (hCRH)-induced ACTH, immunoreactive (ir) beta-endorphin, and cortisol release in normal subjects. Protocols: 1. 30 mg of a slow-release preparation of morphine or placebo was given orally 3 h prior to administration of hCRH (0.1 mg iv) (N = 7). 2. Naloxone (4 mg as bolus iv) or placebo was given 5 min prior to hCRH (N = 7). 3. Naloxone (4 mg iv as bolus followed by a continuous infusion of 6 mg over 75 min) or placebo was started 15 min prior to hCRH (N = 6). hCRH was injected at 11.00 h (protocol 1, 2) or at 17.00 h (protocol 3). Oral morphine not only suppressed basal hormone levels (P less than 0.02), but also the peak response to hCRH compared with placebo (cortisol: 270 +/- 50 vs 559 +/- 80 nmol/l; ACTH: 5.1 +/- 1.5 vs 13.1 +/- 2.7 pmol/l; ir beta-endorphin: 48.5 +/- 8.7 vs 88 +/- 14 pmol/l; mean +/- SEM, P less than 0.02). Similarly, the maximum incremental changes and the area under the curve were significantly reduced for all three hormones compared with placebo (P less than 0.05). After 4 mg of naloxone in the morning, no significant hormonal changes in response to hCRH were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of oral morphine and naloxone on pituitary-adrenal response in man induced by human corticotropin-releasing hormone. 303 66


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