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)

The intermediate lobe of the rat pituitary gland produces a series of peptides related to ACTH and LPH. The spontaneous and isoproterenol-stimulated release of such peptides was studied during in vitro superfusion of rat neurointermediate lobes with Krebs-Ringer medium. Products released into the superfusion medium were quantified by direct measurement or after chromatography on Sephadex G-50. ACTH bioactivity was determined by use of adrenal cortical cell suspension assay. In addition, NH2-terminal ACTH, CO2H-terminal ACTH, alpha-MSH and beta-endorphin radioimmunoassays were used. The results show that 1. neurointermediate lobes of rats secret spontaneously various ACTH- and LPH-related peptides in amounts proportional to the amounts in which these peptides are found in extracts of the neurointermediate lobe; 2. the beta-adrenergic agonist, isoproterenol, stimulated the spontaneous release of various peptides, including alpha-MSH, ACTH, CLIP, glycosylated CLIP, and beta-endorphin-like peptides; 3. isoproterenol induced a dose-dependent (10(-9)-10(-7) M), parallel increase in the release of alpha-MSH and ACTH following similar time courses and showing identical EC50 values (about 10(-8)M). Although the spontaneous release of alpha-MSH and ACTH from rat neurointermediate lobes is not strictly coupled under the conditions used in this study, isoproterenol seems to affect the spontaneous release of these peptides to the same relative extent.
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PMID:beta-Adrenergic stimulation of the release of ACTH- and LPH-related peptides from the pars intermedia of the rat pituitary gland. 611 9

Naturally occurring derivatives of pro-opiomelanocortin (POMC) have been identified in various extra-pituitary sites, including the endocrine and exocrine pancreas. Corticotropin-like intermediate lobe peptide (CLIP = ACTH18-39), a naturally occurring derivative of POMC, has been suggested to be an insulin secretagogue. To determine whether CLIP might also affect the exocrine pancreas, we measured its effect on amylase secretion and protein synthesis and secretion in isolated rat pancreatic lobules. Lobules were dual-pulsed with trace amounts of 14C- and 3H-leucine, both in the presence and absence of CLIP (10(-9)-10(-6) M), using a technique that permitted the labeling of both the synthetic and secretory compartments. The effect of CLIP on protein synthesis was determined by comparing 3H-leucine incorporation into lobules with and without CLIP. The secretory effect of CLIP was determined by measuring (a) secreted 14C-labeled protein as a percent of total incorporated radiolabeled protein, and (b) amylase release into incubation medium. The effect of CLIP on amylase release was compared with that of secretin, cholecystokinin-octapeptide, and carbamylcholine. To localize the biologically active region of CLIP, we similarly studied synthetic ACTH25-39. We demonstrated that CLIP stimulates amylase and protein secretion in a dose-dependent manner and is of similar potency to secretin and carbamylcholine. This effect appears to require the ACTH18-24 region of CLIP and results from stimulus-secretion coupling rather than augmented protein synthesis. We also confirmed the presence of immunoreactive-adrenocorticotropic hormone (IR-ACTH) in rat pancreatic extract using a COOH-terminally directed antibody to ACTH1-39 and demonstrated that this IR-ACTH co-eluted with synthetic CLIP. These findings suggest that CLIP might be an endogenous modulator of pancreatic exocrine function.
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PMID:Effect of corticotropin-like intermediate lobe peptide on pancreatic exocrine function in isolated rat pancreatic lobules. 620 1

Adrenocorticotrophin, lipotrophin and the related peptides alpha-MSH, CLIP, beta-endorphin and met-enkephalin have been measured, and characterized chromatographically in tumour extracts from seven patients with the ectopic ACTH syndrome. Four of the seven tumours contained the complete family of peptides, although the proportion of one to another varied between tumours. In addition, large molecule weight forms of ACTH and met-enkephalin were seen. The potential clinical importance of these observations is discussed.
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PMID:ACTH LPH and related peptides in the ectopic ACTH syndrome. 626 91

The increased production of cortisol by the fetal adrenal gland at term acts as the trigger for parturition in some species. The fetal pituitary controls fetal adrenal function. However, ACTH is only one of a family of closely related peptides which derive from a common precursor and we have shown that although ACTH is the dominant form in the adult pituitary, the expression of the "family trees' is altered in the fetus. In the sheep, it is large-molecular-weight precursors and, in the primate, the smaller peptides such as alpha-MSH, CLIP, beta-MSH and beta-endorphin that predominate in fetal life and which may be responsible for fetal adrenal function. It is still unclear what causes the developmental change in the ACTH "family tree'. Since it may result from a change in pituitary function - from the peptides of the pars intermedia, in the fetus, to those of pars anterior, in the adult - we have studied these two lobes separately in pituitaries taken from adult and fetal sheep and monkeys. Our preliminary results suggest that the change may occur in the neurointermediate lobe in the primate, but that in the sheep the developmental changes occur in the anterior lobe.
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PMID:The pars intermedia and the fetal pituitary-adrenal axis. 626 77

The forms of immunoreactive beta-endorphin-sized material in extracts of anterior and intermediate-posterior pituitary from the rat examined by the ion exchange chromatography method of Zakarian & Smyth. The anterior pituitary primarily contained material that co-migrated with synthetic camel beta-endorphin(1-31), whereas the intermediate-posterior pituitary contained relatively little such material. The majority of immunoactive beta-endorphin-sized peptides in the intermediate pituitary eluted at lower concentrations of NaCl than did camel beta-endorphin. Conditions were developed for the stable, long-term tissue culture of dissociated intermediate-posterior pituitary cells. Extracts of cells maintained in tissue culture for 18 h or nine days had the same content of immunoreactive beta-endorphin, 16k fragment, ACTH(18-39) (or CLIP) and ACTH(17-24). Throughout the nine days in culture, characteristic cells that could be immunostained with antibodies to various regions of pro-ACTH/endorphin were present; during the time in culture, non-reactive background cells multiplied rapidly. The major proteolytic processing of pro-ACTH/endorphin remained characteristic of intermediate pituitary tissue throughout the nine days in tissue culture, and did not become similar to the simpler pattern of proteolytic processing found in the anterior pituitary.
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PMID:Comparison of rat anterior and intermediate pituitary in tissue culture: corticotropin (ACTH) and beta-endorphin. 626 82

Phosphorylated forms of corticotropin[ACTH (1-39)], corticotropin-like intermediary lobe peptide[CLIP, ACTH (18-39)], and the common precursor for ACTH and beta-lipotropin (beta-LPH) have been identified in extracts of rat pituitaries, 32P-Labeled inorganic phosphate was successfully incorporated into ACTH (1-39), CLIP, and the ACTH/beta-LPH precursor in rat neurointermediary lobe explants and into ACTH (1-39) in isolated rat anterior pituitary cells. After peptidase digestion of the labeled CLIP and ACTH, the radioactive phosphate was recoverable as O-phosphoserine. The serine residue at position 31 was the only amino acid found to be phosphorylated in CLIP and ACTH (1-39). The unphosphorylated forms of both peptides were also synthesized. The demonstration of he incorporation of [32P]phosphate into CLIP, ACTH (1-39), and the ACTH/beta-LPH precursor is consistent with the hypothesis that, within the rat intermediary lobe, phosphorylated CLIP is derived from a phosphorylated form of the common precursor, with phosphorylated ACTH (1-39) acting as a biosynthetic intermediate.
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PMID:Biosynthesis of phosphorylated forms of corticotropin-related peptides. 627 71

A 51-year old man presented with the classical features of Cushing's syndrome which had evolved over the previous 5 yr, and was found to have ACTH secretion from an atypical thymic carcinoid tumor. Tumor extract, assayed under conditions designed to prevent artefactual generation of peptides, was found to contain a wide variety of immunoreactive hormones including ACTH, alpha-MSH, CLIP, beta-endorphin and met-enkephalin. The ACTH-related peptides were probably derived from a common precursor, pro-opiocortin, but the presence of met-enkephalin suggests the production of a separate type of precursor molecule. The tumor was locally invasive and, depsite subtotal excision and radiotherapy, continued to secrete large amounts of ACTH. Hypercortisolism was controlled longterm with pharmacological adrenal blockade and steroid replacement.
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PMID:Ectopic secretion of ACTH and met-enkephalin from a thymic carcinoid. 628 29

The isolation and characterization of eight forms of corticotropin-like intermediary lobe peptide (CLIP, adrenocorticotropin18-39) from the intermediary lobe of the rat pituitary has been accomplished by using reversed phase high performance liquid chromatography. The eight forms are the result of all combinations of the presence or absence of three post-translational modifications. These are glycosylation, phosphorylation, and removal of the carboxyl-terminal amino acid. The sites of phosphorylation and glycosylation are at serine 31 and asparagine 29, respectively. The eight forms (in order of elution from the reversed high performance liquid chromatography column) are glycosylated, phosphorylated CLIP18-38; glycosylated, nonphosphorylated CLIP18-38; nonglycosylated, phosphorylated CLIP18-38; nonglycosylated, nonphosphorylated CLIP18-38; glycosylated, phosphorylated CLIP18-39; glycosylated, nonphosphorylated CLIP18-39; nonglycosylated, phosphorylated CLIP18-39; and nonglycosylated, nonphosphorylated CLIP18-39.
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PMID:Characterization of eight forms of corticotropin-like intermediary lobe peptide from the rat intermediary pituitary. 628 38

Immunohistochemical studies on the pituitary of Anolis carolinensis detected ACTH-like, beta-endorphin-like, and 16K fragment-like immunoreactivity in distinct clusters of cells in the anterior lobe; ACTH-like, alpha MSH-like, beta-endorphin-like, and 16K fragment-like immunoreactivity was detected in all the cells of the intermediate lobe. Crude acid extracts of both lobes, when analyzed by radioimmunoassay, gave displacement curves in ACTH and beta-endorphin assays which were parallel to the appropriate synthetic standard. Only extracts of the intermediate lobe gave parallel displacement curves in an alpha MSH radioimmunoassay. Extracts of both lobes crossreacted with antiserum to 16K fragment, but the displacement curves were not parallel to that of mouse 16K fragment standard. The levels of immunoreactive ACTH and beta-endorphin in the intermediate lobe were approximately 8-fold higher than in the anterior lobe. Fractionation of anterior lobe and intermediate lobe extracts by either gel filtration on Sephadex G-75 in 10% formic acid or sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed multiple forms of ACTH-related and beta-endorphin-related substances in both lobes. In the anterior lobe the major forms of immunoreactivity were, respectively, ACTH-sized and beta-endorphin-sized. In the intermediate lobe the major forms of immunoreactivity were alpha MSH-sized, CLIP-sized, and beta-endorphin-sized. In both lobes, antisera directed against ACTH and beta-endorphin detected high molecular weight material with an apparent molecular weight slightly less than that of mouse pro-ACTH/endorphin; this material probably represents the putative common precursor for ACTH and beta-endorphin in this species.
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PMID:Localization of multiple forms of ACTH- and beta-endorphin-related substances in the pituitary of the reptile, Anolis carolinensis. 630 Aug 7

Possible physiological factors that might control the extent of phosphorylation of ACTH-related peptides in the rat pituitary were investigated both in vivo and with cultured anterior or neurointermediate pituitary cells. Phosphorylated and nonphosphorylated forms of ACTH and corticotropin-like intermediate lobe peptide [CLIP or ACTH(18-39)] were separated by isoelectric focusing or high performance liquid chromatography and quantified by immunoassay. Radiolabeled ACTH- or CLIP-related peptides from cultured pituitary cells incubated in [3H]tyrosine were isolated by immunoprecipitation or immunoadsorption, fractionated as above, and detected by liquid scintillation counting. Both in the animal and in culture, the extent of phosphorylation of anterior pituitary cellular ACTH did not vary when the release of ACTH was stimulated (by metyrapone treatment, corticotropin-releasing factor, or cAMP) or inhibited (by dexamethasone). Long term cultures of rat anterior pituitary cells continued to phosphorylate ACTH in both serum-containing and serum-free medium; the extent of phosphorylation of ACTH rose from about 55% in vivo to 80% within 1 week in culture. By comparison, the extent of phosphorylation of intermediate pituitary CLIP decreased from about 75% in vivo to about 40-50% in culture. The extent of phosphorylation of the ACTH and CLIP secreted by primary pituitary cultures simply reflected the extent of phosphorylation of ACTH and CLIP in the cells, in both basal and stimulated states. Human ACTH(1-39) contains the same amino acid sequence that is phosphorylated in rat and mouse ACTH(1-39). Based on isoelectric focusing and high performance liquid chromatography of the tryptic peptides of human ACTH (with and without alkaline phosphatase treatment), about one third of the ACTH in the human pituitary is phosphorylated.
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PMID:Phosphorylation of rat and human adrenocorticotropin-related peptides: physiological regulation and studies of secretion. 630 52


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