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

Groups of female rats were injected daily for 14 days with 10 mg of cortisone acetate subcutaneously, to study the mechanisms of glucocorticoid suppression on the hypothalamic-pituitary-adrenal axis. Pituitary adrenocorticotropic hormone (ACTH) content, plasma ACTH, adrenal venous corticosterone, adrenal weights, and the catabolic effects on body weight were studied simultaneously (under stressful and non-stressful conditions) before, during, and up to six weeks after cortisone. This study confirmed the results of other investigators that cortisone acetate caused catabolic weight loss and adrenal atrophy, but it was noted to persist up to six weeks after the injections. Glucocorticoid acetate was more effective in causing ACTH-axis suppression than succinate or phosphate preparations, and the effects were dose and time related. Significant depletion of pituitary ACTH content, suppression of plasma ACTH, and corticosterone secretion occurred five to seven days after beginning cortisone acetate (p=<0.001); it was continuous throughout the injection schedule (p=<0.001); it remained for two to four weeks after the cortisone was discontinued (p=<0.001). The animals showed minimum plasma ACTH responsiveness to severe acute stress during this two to four-week suppression phase, but rapid recovery occurred thereafter. Plasma ACTH was undetectable up to six weeks post-cortisone when the animals were not under stress. This may be related to residual cortisone acetate found at the injection sites, or to an altered or different ACTH-axis control mechanism. The sequence of events during recovery from cortisone suppression appeared to be (1) repletion of corticotrophin-releasing hormone (by inference), (2) repletion of pituitary ACTH content, (3) secretion of plasma ACTH, (4) reversal of adrenal atrophy, and (5) subsequent secretion of corticosterone.
 ...
PMID:Suppression of the hypothalamic-pituitary-adrenal axis after subcutaneous cortisone acetate administration in rats. 22 95

The high molecular weight forms of adrenocorticotropic hormone (ACTH) produced by mouse pituitary tumor cells (AtT-20/D-16v) were separated from each other by gel filtration; their ability to stimulate steroidogenesis by isolated rat adrenal cortical cells was studied. Pools of pro-ACTH/endorphin. ACTH biosynthetic intermediate, and glycosylated ACTH(1--39) were obtained; on the basis of NaDodSO4-polyacrylamide gel electrophoresis, over 97% of the immunoactive ACTH was found to have the expected molecular weight. Suspension of isolated rat adrenal cortical cells were incubated overnight in tissue culture medium and used in a 2-h steroid production assay. Synthetic human ACTH(1--39) [hACTH(1--39)] was used as a bioassay and immunoassay standard; 60 pM hACTH(1--39) stimulated half-maximal production of fluoregenic steroid. The amount of pro-ACTH/endorphin, ACTH biosynthetic intermediate, or glycosylated (ACTH(1--39) added was estimated with an ACTH(17--24) immunoassay. All three high molecular weight forms of ACTH are capable of stimulating the same maximal level of steroidogenesis as hACTH(1--39). Glycosylated ACTH(1--39) is equipotent with hACTH(1--39); ACTH biosynthetic intermediate and pro-ACTH/endorphin are, respectively, 100- and 300-fold less potent than hACTH(1--39). Steroid production in response to all four forms of ACTH is linear in time. All of the different forms of ACTH stimulate the synthesis of corticosterone and related steroids; no significant production of cortisol or aldosterone was observed. beta-Lipotropin (beta LPH) and 16K fragment, which comprise the non-ACTH regions of pro-ACTH/endorphin and are secreted by the pituitary tumor cells, did not stimulate or interfere with steroidogenesis. Brief incubations of pro-ACTH/endorphin and ACTH biosynthetic intermediate with trypsin generated lower molecular weight forms of ACTH and increased biological activity 50-fold; thus, the decreased steroidogenic potency of these forms of ACTH is thought to be due to structural constraints on the ACTH(1--39)-like sequence in these larger precursor molecules
 ...
PMID:Steroidogenic activity of high molecular weight forms of corticotropin. 22 22

1 The response of adrenal blood flow to adrenocorticotropic hormone (ACTH) was measured with radioactive microspheres in anaesthetized, dexamethasone-treated, mongrel dog. 2 Adrenocorticotropic hormone (2 u/h i.v.) increased adrenal blood flow within 15 min and this persisted for the duration of the infusion. 3 Cortisol concentrations also rose with ACTH infusion. 4 Indomethacin (6 mg/kg i.v. followed by 1 mg/min) did not effect the adrenal response to ACTH although plasma concentrations of indomethacin (21.9 +/- 2.5 micrograms/ml) adequate to suppress prostaglandin synthesis were achieved. 5 We conclude that prostaglandins are not required for steroidogenesis or the adrenal haemodynamic response to ACTH.
 ...
PMID:The failure of indomethacin to alter ACTH-induced adrenal hyperaemia or steroidogenesis in the anaesthetized dog. 22 11

Isolated intermediate lobe cells from 40 rat pituitaries were incubated for 3 h with [35S]methionine + [3H]-phenylalanine, [35S]methionine, [3H]valine, and [3H]leucine. The cell extracts were purified by carboxymethyl-cellulose chromatography (CMC) and the fraction eluting with ovine adrenocorticotropic hormone (ACTH) was further purified either by another CMC under the same conditions or by high performance liquid chromatography (HPLC). Microsequencing of the product from the second CMC allowed the identification of a peptide containing methionine 4 and phenylalanine 7, as expected for the NH2 terminus of ACTH. Purification by HPLC of a similar peptide obtained from the three other incubations gave three main raoactive peaks which were further characterized by their migration rates on polyacrylamide gels, molecular weight, and microsequencing. Results indicated that intact ACTH (residues 1-39) is present in extracts of rat intermediate lobe, but in very small quantities (less than 1% of the beta-endorphin content). ACTH is probably broken down into smaller fragments, e.g. alpha-melanocyte-stimulating hormone (alpha-MSH) (ACTH, 1-13) and corticotropin-like intermediate lobe peptide (CLIP) (ACTH, 18-39). These studies also revealed with existence of a peptide having identical sequence with the (N-1) terminus of the ACTH/lipotropin (LPH) precursor.
 ...
PMID:Biosynthesis and characterization of adrenocorticotropic hormone, alpha-melanocyte-stimulating hormone, and an NH2-terminal fragment of the adrenocorticotropic hormone/beta-lipotropin precursor from rat pars intermedia. 22 83

1. Administration of adrenocorticotropic hormone (ACTH) to sheep produced increases in mean arterial pressure within 24 h associated with an increase in cardiac output and cardiac rate. Both cardiac output and blood pressure remained elevated over the 5 days of ACTH treatment. 2. Administration of ACTH during beta-adrenoreceptor blockade resulted in an increase in blood pressure without changes in cardiac output at 24 h. 3. Administration of a combined steroid infusion over 5 days produced increases in cardiac output identical with the effects of ACTH but with a substantially smaller effect on blood pressure. 4. These data suggest that the observed changes in cardiac output produced by ACTH treatment may be associated with high blood concentrations of adrenocortical steroids rather than being necessary for the development of the hypertension.
 ...
PMID:Haemodynamics of ACTH-induced hypertension in sheep. 23 25

Cushing's disease developed in a 5-year-old girl with acute lymphoblastic leukemia 18 months after her last therapeutic exposure to adrenal glucocorticosteroids. Obesity, hyperpigmentation, striae, osteoporosis, and hirsutism were accompanied by elevated levels of plasma cortisol. These showed no diurnal fluctuation and they were not suppressed by dexamethasone. At autopsy, the adrenal glands were enlarged and the pituitary gland showed increased numbers of basophils of the adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormone secreting type. Leukemic infiltrates in brain tissue were prominent in the hypothalamus and in the limbic system. It is postulated that the destructive leukemic infiltrate of the limbic system removed a restraining influence on pituitary function, with basophilic hyperplasia, ACTH hypersecretion, adrenocortical hypertrophy, and clinical Cushing's disease the consequences.
 ...
PMID:Cushing's syndrome and acute lymphoblastic leukemia. 27 79

Evidence for the existence of a hormone that is stimulable by adrenocorticotropic hormone (ACTH) and capable of causing hypertension has been collected in several patients. This hormone is not a known mineralocorticoid or glucocorticoid. The hypothesis that a steroid can produce hypertension was tested in an 18-year-old man with dexamethasone-suppressible hypertension. During dexamethasone treatment, when aldosterone secretion was suppressed, less than normal and the patient was normotensive, steroids were given by constant infusion in an attempt to reproduce the hypertension of the dexamethasone-free state. Hypertension was not caused by 5 days of administration of aldosterone, 18-hydroxydeoxycorticosterone (18-OH-DOC) at 1 mg/day, or deoxycorticosterone (DOC) at 30 mg/day. However, sodium retention and potassium loss were observed during infusion of aldosterone and DOC. Hypertension was produced within 5 days during infusion of ACTH or oral metyrapone. The hypertensive effect of the metyrapone was eliminated by the additional treatment with aminoglutethimide. These studies suggest that an ACTH-dependent steroid rather than aldosterone, 18-OH-DOC, or DOC may be the cause of the hypertension in this patient. Study of a 3-year-old child who presented with short stature, hypertension, hypokalemic alkalosis, suppressed renin and ACTH, and decreased excretion of all known steroids suggested excessive secretion of a pressor hormone. Reversal of the hypertension and hypokalemic alkalosis occurred when spironolactone was administered. ACTH exacerbated the clinical and biochemical abnormalities, suggesting that the secretion of the unknown factor was dependent on ACTH. A study of the urinary steroids revealed remarkably low excretion of aldosterone and cortisol. Plasma levels of ACTH were low. The low production of aldosterone was not associated with the increased excretion of precursor metabolites. These finding suggest the secretion of an unknown hypertensive factor of remarkably high potency, with the ability to suppress the secretion of both renin and ACTH.
 ...
PMID:Mineralocorticoid hypertension in childhood. 32 86

The influence of the hippocampus upon pituitary release of adrenocorticotropic hormone (ACTH) was studied in male Sprague-Dawley rats which had concentric bipolar stainless stell electrodes chemically implanted in the dorsal and ventral hippocampus. Blood samples were withdrawn at half-hour intervals from a cannula in the right atrium. Plasma corticosterone levels reflected ACTH release. 30 min of 25 or 250-cps electrical stimulation of the hippocampus in the freely-behaving, non-stressed rat resulted in significant increases in basal plasma corticosterone levels evident at the end of stimulation. In afternoon experiments, after stimulation at either hippocampal site with 25 cps only, the increase was followed by a delayed inhibitroy phase and temporary inhibition of the circadian rise in corticosterone levels. The inhibitory effect was more pronounced with ventral than with dorsal hippocampal stimulation. The basis for these differential effects is discussed in terms of the anatomical organization of the hippocampus.
 ...
PMID:Effect of electrical stimulation of the hippocampus upon corticosteroid levels in the freely-behaving, non-stressed rat. 93 26

A 4-year-old girl had abdominal distention, muscular weakness, renal tubular dysfunction, and hypertension associated with hypokalemic metabolic alkalosis. There were no clinical symptoms of cortisol deficiency, but there was excessive deoxycorticosterone and cortisocsterone production. Basal plasma aldosterone levels were undetectable; however, adrenocorticotropic hormone (ACTH) stimulation brought plasma aldosterone levels up to normal. The urinary pregnanediol, tetrahydro-deoxycorticosterone (THDOC), and tetrahydrocorticosterone (THB) concentrations were elevated. Stimulation of ACTH failed to increase urinary 17-ketosteroid, 17-hydroxycorticosteroid, or plasma cortisol levels significantly, while urinary THDOC, THB, and plasma corticosterone concentrations were further elevated. The elevated plasma corticosteroid intermediates were suppressed by dexamethasone administration. When physiologic doses of dexamethasone were administered, the hypertension, electrolyte imbalance, and abnormal corticosteroid secretion were all corrected. The studies indicated a partial 17alpha-hydroxylase defect in this patient.
 ...
PMID:Hypokalemic crisis simulating intestinal obstruction in a 4-year-old girl. A consequence of 17alpha-hydroxylase deficiency. 97 20

Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC profile of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide completely inhibited the adrenal steroidogenesis stimulated by ACTH and by the high-affinity MDR ligand 4'-chlorodiazepam.
 ...
PMID:Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland. 127 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>