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)

A patient with Addison's disease, treated with conventional hydrocortisone replacement, developed deep hyperpigmentation, headache and vomiting. Plasma adrenocorticotropin (ACTH) level was extremely high, showing abnormal diurnal rhythm. Suppression of ACTH with glucocorticoids was attenuated and the responses to ovine corticotropin-releasing hormone (oCRF) and lysine vasopressin (LVP) were absent. Magnetic resonance imaging (MRI) suggested an enlargement of the pituitary gland, while immunohistological examination of pituitary fragments obtained by transsphenoidal surgery revealed corticotroph hyperplasia without microadenoma. Postoperatively, plasma ACTH returned to normal and adequately responded to oCRF and LVP. Over the year since surgery, the symptoms have gradually improved and the patient has resumed normal activities.
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PMID:Inappropriate secretion of adrenocorticotropin from corticotroph hyperplasia in a case of Addison's disease. 217 Jul 22

The existence of feedback inhibition of ACTH on its own secretion has been postulated. To investigate its existence in man, the effects of synthetic ACTH 1-24 on endogenous ACTH secretion were tested in 13 patients with Addison's disease. Plasma ACTH was measured using an immunoradiometric assay, specific for endogenous ACTH 1-39. Ten patients were given 50 micrograms ACTH 1-24 as a bolus iv dose followed by a 50-microgram infusion in 90 min. Blood samples for ACTH and cortisol assay were obtained at 0, 15, 30, 60, 90, and 120 min. As a control, a saline infusion was given 2 days earlier. Three other patients were given 100 micrograms ovine corticotropin-releasing hormone (oCRH) iv and ACTH 1-24 as described above. Blood samples for ACTH and cortisol assay were drawn every 15 min for 2 hours. A CRH test was performed during saline infusion as a control 2 days earlier. In all patients steroid replacement therapy was maintained during the studies. ACTH 1-24 caused a significant decrease (P less than 0.01) in endogenous plasma ACTH at 15 min compared to saline. oCHR administration markedly stimulated ACTH release in the three patients tested, and the ACTH response to oCRH was completely inhibited by the simultaneous administration of ACTH 1-24. These findings strongly support the presence of ACTH autoregulation in man. The complete inhibition of the ACTH response to oCRH by exogenous ACTH 1-24 provides evidence for ultra-short feed-back inhibition at the pituitary level.
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PMID:Evidence for ultra-short loop autoregulation of adrenocorticotropin secretion in man. 282 4

The effect of loperamide - a peripheral opiate agonist - on plasma ACTH response to Corticotropin-releasing Hormone (CRH) has been investigated in 6 patients with Addison's disease. After placebo administration CRH induced a marked ACTH increase. After loperamide administration ACTH levels fell to a nadir of 135 +/- 76 pg/ml, and then CRH was still able to induce an ACTH increase; the pattern of ACTH response to CRH was slightly delayed. There was a significant difference between the two ACTH curves after CRH only in the early phase of the response. These data suggest that the inhibitory role of loperamide on ACTH secretion is exerted at supra-pituitary level, although a pituitary site of action can not be excluded.
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PMID:Loperamide modifies but does not block the corticotropin-releasing hormone-induced ACTH response in patients with Addison's disease. 283 97

Synthetic corticosteroids are frequently used to manage asthma and other inflammatory diseases. The timing of such drugs (whether ingested, inhaled, or infused) in relation to body rhythms influences the magnitude of both desired and undesired effects. It is crucial that corticotherapy be correctly scheduled to the circadian system of the hypothalamic-pituitary-adrenocortical (HPA) system. The secretion of cortisol from the adrenal cortex is not constant during each 24-hour period. Instead, production of this hormone varies as a high-amplitude circadian rhythm, with most of the secretion taking place during the initial hours of the activity span and very little late in the evening and during the first half of the sleep span. Results of laboratory and human studies indicate that the timing of exogenous corticosteroids, in relation to the circadian rhythm in HPA activity, is a critical factor. For example, the optimization of corticosteroid therapy for asthmatics entails daily (or alternate-day) administrations in the morning and, if necessary, early afternoon. By timing exogenous corticosteroids early during the activity span, the risk of adrenal suppression is minimized or avoided while bronchial patency is optimally enhanced, i.e., increasing the 24-hour average forced expiratory volume in 1 second (FEV1) and reducing its nocturnal dip. Clinical findings indicate that these results are obtainable with both acute and chronic corticosteroid therapies. In contrast, splitting the daily dose of corticosteroids into several small administrations, such as at mealtimes and before bedtime, markedly increases the likelihood of adrenal suppression without achieving the desired therapeutic effect. The dosing of synthetic corticosteroids late in the afternoon or evening, whatever the route of delivery, suppresses pituitary adrenocorticotropic hormone (ACTH) production during subsequent 24-hour spans, resulting in adrenocortical inhibition. Also, morning dosing of corticosteroids over many years seems to induce less--if any--osteopenia compared to dosing at other times. The adrenal response to exogenous administration of ACTH also is circadian-rhythmic. ACTH dosing in the morning results in greatest adrenal response in terms of cortisol secretion, while dosing in the evening results in least response. Knowledge of the circadian organization of the HPA axis is necessary to optimize the effect of synthetic corticosteroids, whether they be used to treat asthma, rheumatoid arthritis or other cortico-dependent diseases, or as a substitution therapy for Addison's disease.
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PMID:Chronobiology and asthma. III. Timing corticotherapy to biological rhythms to optimize treatment goals. 284 6

Loperamide is a peripheral opiate agonist able to inhibit ACTH secretion. In this work, the interactions between loperamide and two ACTH secretagogues, lysine vasopressin (LVP) and corticotropin-releasing hormone (CRH), were investigated in patients with Addison's disease. After loperamide (16 mg orally) or placebo administration, 5 patients received LVP (0.06 IU/kg i.v. over 1 h) and 6 patients received oCRH (1 micrograms/kg i.v. as bolus). In all patients loperamide induced a significant fall in plasma ACTH levels. LVP increased ACTH levels after both loperamide (from 48 +/- 17.3 to a peak of 95 +/- 21 pmol/l) and placebo (from 231 +/- 59.5 to 365 +/- 86.6 pmol/l): the interaction between treatments and time was not significant. CRH caused a rise in plasma ACTH after both loperamide (from 30 +/- 16.6 to a peak of 108 +/- 31 pmol/l) and placebo (from 98.5 +/- 47 to 211 +/- 61.7 pmol/l): the interaction between treatments and time was significant, and the first phase of CRH-induced ACTH secretion was significantly lower after loperamide. These data demonstrate that loperamide differently modifies the stimulatory action of LVP and CRH on ACTH secretion: namely, LVP and loperamide act in an additive manner, while CRH and loperamide interact in a non additive way. Although these findings might be explained by the involvement of different intracellular ACTH-secreting mechanisms, an influence of loperamide on some suprapituitary factors modulating the ACTH response is suggested.
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PMID:Loperamide, an opiate analog, differently modifies the adrenocorticotropin responses to corticotropin-releasing hormone and lysine vasopressin in patients with Addison's disease. 285 5

There is evidence that peptides related to alpha-melanocyte-stimulating hormone (alpha-MSH) are involved in regulating the zona glomerulosa of the adrenal cortex in certain species. We have investigated the amount of immunoreactive (IR)-alpha-MSH in the human pituitary gland of patients suffering from Addison's disease. We show increased numbers of cells containing demonstrable IR-alpha-MSH in the anterior lobe in these patients. Using an antiserum with specificity for the acetylated N-terminus of alpha-MSH we suggest that the major form present is desacetyl-alpha-MSH. These findings are in keeping with a role for anterior lobe derived desacetyl-alpha-MSH in the regulation of the human adrenal cortex.
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PMID:Increased production of alpha-melanocyte-stimulating hormone in the pituitary gland of patients with untreated Addison's disease. 285 22

Synthetic ovine corticotropin-releasing factor (o-CRF) stimulated adrenocorticotropin (ACTH) release at the concentration of 10(-10) M or more in monolayer culture of rat anterior pituitary cells. Dexamethasone, 10(-7) M, inhibited this effect. In 5 healthy human subjects, o-CRF, 1 microgram/kg iv bolus, increased plasma ACTH levels from less than 10 pg/ml to 40.4 +/- 11.0 (mean +/- SD) after 30-60 min, and plasma cortisol from 12.8 +/- 2.8 micrograms/dl to 23.6 +/- 3.1 after 45-60 min. Of 7 patients with Cushing's disease (CD), five showed an exaggerated response of plasma ACTH and cortisol, one an exaggerated response of plasma ACTH but low response of plasma cortisol and the other no response of both hormones. The significant positive correlation between the inhibition of plasma cortisol by dexamethasone and the response of plasma ACTH and cortisol to o-CRF in CD was seen. No response of plasma ACTH and cortisol to o-CRF was seen in each one patient with Cushing's syndrome due to an adrenocortical adenoma, ectopic ACTH syndrome (but low response at retesting), isolated ACTH deficiency and Sheehan's syndrome. In one patient with Addison's disease an exaggerated response of plasma ACTH but no response of plasma cortisol was seen. In 4 of 5 healthy subjects and 5 of 7 patients with CD, plasma ACTH and cortisol levels showed a second peak at 120--210 min after o-CRF administration. To clarify the prolonged effect of o-CRF in human in vivo, the disappearance rates of injected o-CRF were evaluated by radioimmunoassay in 3 patients with cured Cushing's syndrome. A biexponential decay curve showed t1/2 values of 9.3 +/- 0.4 min and 79.6 +/- 0.7 min (mean +/- SE). From the chromatographic profile, a portion of injected o-CRF was thought to be bound to macromolecule (s). o-CRF, as a specific secretagogue of ACTH, is thought to be useful tool in evaluating patients with hypothalamo-pituitary-adrenal disorders.
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PMID:[Studies for clinical application of ovine corticotropin-releasing factor]. 298 91

Addison's disease is an uncommon disorder whose dermatologic manifestations range from vitiligo to hyperpigmentation. The association of adrenal autoantibodies and vitiligo has made the latter a possible cutaneous marker for an autoimmune cause. The other cutaneous marker, hyperpigmentation, is now more clearly understood on the basis of a prohormone common to both adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating hormone (MSH).
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PMID:Hyperpigmentation, vitiligo, and Addison's disease. 299 3

To ascertain the physiological relevance of an autoregulation of adrenocorticotropin hormone(ACTH) secretion in man, we studied the effect of alsactide (beta-Ala1, Lys17-ACTH1-17-4-amino-N-butylamide), a synthetic ACTH analogue with potent steroidogenic activity but not recognized in the endogenous ACTH immunoassay, on plasma ACTH pattern in patients with Addison's disease. Three experimental models were employed as follows: (a) in 6 patients, whose steroid replacement therapy had been discontinued 36 h previously, we compared the effect of alsactide, administered at two dose levels (10 or 100 micrograms i.v. als bolus followed by the same dose infused over 2 h, and of placebo, on the plasma ACTH pattern; (b) the previous experiment was repeated in 4 patients in whom cortone replacement therapy was substituted for 3 days with dexamethasone, 0.5-1.5 mg daily p.o., so as to lower plasma ACTH levels to within the high normal range; (c) in 4 patients off therapy for 36 h, we evaluated the ACTH response to synthetic ovine corticotropin-releasing factor, 1 microgram/kg body weight injected intravenously, occurring during concomitant administration of alsactide, 100 micrograms i.v. as bolus plus 100 micrograms infused over 2 h, or placebo. Compared to placebo, alsactide did not significantly affect the pattern of ACTH under any of the experimental conditions investigated. Collectively, our findings, although they have to be interpreted with caution, do not support the idea that a self-regulation mechanism plays an important role in the control of ACTH secretion in man.
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PMID:Evidence against a self-inhibition of ACTH secretion in man. 300 62

The cytoplasmic secretory granules of corticotrophs in the anterior pituitary are basophil in trichrome stains and periodic acid-Schiff positive in the histochemical stain for glycoprotein due to their content of the glycosylated 16 000 N-terminal fragment of the precursor protein proopiomelanocorticotrophin (POC). The granules show a positive immunocytochemical reaction to antibodies raised against ACTH, beta-endorphin and N-terminal fragments of POC. A small subset of corticotrophs contains immunoreactive alpha MSH in addition. Immunocytochemistry shows the corticotrophs to constitute about 15-20% of the anterior pituitary cells arranged both singly and in clumps. They are distributed in the median wedge and anteriorly, laterally and posteriorly adjacent to the pars nervosa which is often 'invaded' by corticotroph basophils. The alpha MSH subset is prominent in the rudimentary intermediate lobe and is scattered anteriorly in the pituitary of the human fetus. Crooke cell hyalinization is associated with pathologically maintained hypercortisolaemia and with glucosteroid therapy. The hyalinization is demonstrated in ultrastructure to be due to massive accumulation of intermediate cytoplasmic filaments 7-8 nm in diameter that are normally present in only small number. The change is associated with a varying degree of loss of secretory granules. In untreated Addison's disease there is a marked increase in the number of corticotrophs, many of which are arranged in distended alveoli to form micronodules. The vast majority of cases of pituitary-dependent Cushing's disease and all cases of Nelson's syndrome are associated with a basophil or chromophobe adenoma. These give a positive immunocytochemical reaction with anti-ACTH, beta-endorphin and N-terminal POC. In ultrastructure the cells of the chromophobe adenomas are seen to contain sparse secretory granules that are usually smaller than those in the chromophil adenomas. There are only very few reports of pituitary-dependent Cushing's disease found to be due to immunocytochemically confirmed corticotroph hyperplasia with or without a corticotroph adenoma. A few cases have been described in which the adenoma cells show Crooke's hyalinization, associated in one example with secretion of a big ACTH found more typically in ectopic ACTH-secreting tumours. A group of cases due to corticotroph adenoma has been reported whose excessive ACTH secretion is reduced by treatment with the dopamine agonist bromocriptine, in which it is suggested that the tumour cells arise from a subset of corticotrophs of pars intermedia origin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Histopathology of the pituitary. 300 76


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