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)

This report concerns ontogenetic aspects of the production and in vitro release of NH2-terminally acetylated forms of melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin by the pars intermedia of the pituitary gland of the mouse. In vitro biosynthetic analysis and radioimmunoassay revealed that approximately 12 h before birth most of the MSH in the fetal pars intermedia is present as des-N alpha-acetyl alpha-MSH. The same non-acetylated peptide is at this stage also the major release form of melanotropin. In 1-day-old mice the level of alpha-MSH and diacetylated alpha-MSH had increased considerably, although des-N alpha-acetyl alpha-MSH remained the major form. Five days after birth alpha-MSH and its diacetylated form constitute the major tissue and release form of the peptide, a situation very similar to that in adult mice. Acetylation of beta-endorphin appeared to occur earlier in development, N alpha-acetyl beta-endorphin (1-31) being the major form of endorphin already in the fetal pars intermedia. It is concluded that in the mouse acetylation of melanotropin and acetylation of beta-endorphin are not necessarily concomitant events. It could be established that the ability of the pars intermedia cells for cleaving N alpha-acetyl beta-endorphin (1-31) to yield C-terminally shortened forms of beta-endorphin develops after birth.
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PMID:Acetylation of melanocyte-stimulating hormone and beta-endorphin in the pars intermedia of the perinatal pituitary gland in the mouse. 294 92

Lipotropin and peptides related to beta-endorphin were extracted from the anterior pituitary and the pars intermedia of porcine pituitary and were resolved by gel exclusion and ion exchange chromatography. Possible heterogeneity in the structure of the lipotropin was investigated by identifying the C-terminal fragment released by limited proteolysis with trypsin; the cleavage was restricted to the carboxyl group of arginine residues by employing citraconylation to protect the epsilon-NH2 groups of lysine. The lipotropin obtained from both regions of the pituitary gave rise to the same C-terminal peptide which contained the 31-residue sequence of beta-endorphin; none of the 26- and 27-residue forms was detected. In contrast, the beta-endorphin-related peptides that were isolated directly from the pars intermedia exhibited a high degree of C-terminal proteolysis: they were present principally as the 26- and 27-residue peptides. The results demonstrate that lipotropin differs from beta-endorphin in that it occurs exclusively in the form that contains the full C-terminal sequence. It is concluded that during biosynthesis lipotropin undergoes conversion to beta-endorphin before proteolysis takes place at the C-terminus. The processing reactions that convert lipotropin to beta-endorphin 1-31 and beta-endorphin 1-31 to beta-endorphin 1-27 are thus ordered and not competitive. The results also indicate that glycylglutamine, the bioactive C-terminal dipeptide of lipotropin, is formed from beta-endorphin and not from lipotropin.
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PMID:Sequential formation of beta-endorphin-related peptides in porcine pituitary. 296 43

Within the past year, three similar peptides with specific growth hormone (GH) releasing effects have been extracted from human tissue, identified, and synthesized. Human pancreatic tumor GH releasing factor (I-40)-OH (hpGRF-40) was the sole hpGRF isolated from the pancreatic tumor of a patient in Charlottesville and was the predominant peptide isolated from the pancreatic tumor of a patient in Lyon. The Lyon tumor also contained hpGRF(1-37)-OH and hpGRF(1-44)-NH2. Both immunological and biochemical data suggest that hpGRF-40 and hpGRF-44 are present in the human hypothalamus and may be the human GH releasing hormone(s) (GHRH). In cultures of rat pituitary cells, hpGRF stimulates GH but affects neither basal and dopamine-inhibited prolactin release nor basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. hpGRF stimulates cyclic AMP production within seconds, an effect which is blocked by somatostatin. In contrast, while hpGRF stimulates phosphatidylinositol turnover in the pituitary, the effect is not inhibited by somatostatin. In the human, hpGRF-40 (1 microgram/kg) given intravenously (i.v.) stimulates GH release within 5 minutes. hpGRF-40 does not elevate serum prolactin levels, thyrotropin (TSH), LH, or corticotropin (measured indirectly through plasma cortisol), or blood glucose or plasma concentrations of insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, or somatostatin. When graded doses of hpGRF (0.1-10 micrograms/kg) are given i.v., no differences are noted in the maximal levels of serum GH achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human pancreatic tumor GH-releasing factor. 298 23

Pro-opiomelanocortin (adrenocorticotropin/endorphin prohormone) is processed to yield active hormones by cleavages at paired basic amino acid residues. In this study, an enzyme that specifically cleaves at the paired basic residues of this prohormone has been purified from bovine pituitary intermediate lobe secretory vesicles, the intracellular processing site of proopiomelanocortin. This enzyme, named pro-opiomelanocortin converting enzyme, has been characterized as a glycoprotein of Mr approximately 70,000. It has an apparent isoelectric point between 3.5 and 4.0. The pH optimum of the pro-opiomelanocortin converting enzyme is between 4 and 5, but the enzyme is highly active at the intravesicular pH of 5.1-5.6. The enzyme specifically cleaved the Lys-Arg pairs of pro-opiomelanocortin to yield Mr = to 21,000-23,000 ACTH, beta-lipotropin, Mr 13,000 and 4,500 ACTH, beta-endorphin, and a Mr = 16,000 NH2-terminal glycopeptide, the products synthesized by the pituitary intermediate lobe in situ. NH2- and COOH-terminal analysis of the products indicated that the pro-opiomelanocortin converting enzyme cleaves the peptide bond either between the Lys and Arg or on the carboxyl side of the Arg at Lys-Arg pairs of pro-opiomelanocortin. The intracellular localization, pH optimum, and cleavage specificity of the enzyme suggest that it may function as a pro-opiomelanocortin processing enzyme in the pituitary intermediate lobe in vivo.
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PMID:Purification and characterization of a paired basic residue-specific pro-opiomelanocortin converting enzyme from bovine pituitary intermediate lobe secretory vesicles. 298 47

alpha-Melanotropin (alpha-melanocyte stimulating hormone, alpha-MSH) stimulates tyrosinase activity in Cloudman S91 murine melanoma cells. Three [Nle4, D-Phe7]-substituted alpha-melanotropin analogues, [Nle4, D-Phe7]-alpha-MSH, Ac-[Nle4, D-Phe7]-alpha-MSH4-11-NH2, and Ac-[Nle4, D-Phe7]-alpha-MSH4-10-NH2, are at least 100-fold more effective than alpha-MSH in stimulating melanoma tyrosinase, the rate-limiting enzyme in melanin biosynthesis. These [Nle4, D-Phe7]-substituted melanotropin analogues induce tyrosinase activity in melanoma cells with shorter contact times than required by the native hormone, alpha-MSH. [Nle4, D-Phe7]-substituted melanotropins also induce a prolonged (residual) stimulation of melanoma tyrosinase. Following incubation of melanoma cells in the presence of [Nle4, D-Phe7]-alpha-MSH for 24 h, tyrosinase activity is maintained for up to 6 days in the absence of the melanotropin. The shorter 4-10 and 4-11 fragment analogues also exhibit residual melanotropic activity. The prolonged stimulation of tyrosinase in the absence of the analogues is maintained even though melanoma cells continue to divide about every 24 h. These results suggest that melanoma cells possess spare melanotropin receptors and that [Nle4, D-Phe7]-substituted analogues bind almost irreversibly to these receptors or to some other component of the adenylate cyclase enzyme complex responsible for enhancing tyrosinase activity and melanin production.
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PMID:Prolonged stimulation of S91 melanoma tyrosinase by [Nle4, D-Phe7]-substituted alpha-melanotropins. 299 67

New syntheses of three thyrotropin releasing hormone (TRH) analogues ([Dopa2]THR, [Nic1]TRH, and [Tyr(30NO2)2]TRH) have been reported (Dopa stands for L-3,4-dihydroxyphenylalanine, Nic--for nicotinic acid and Tyr(3-NO2)--for L-3-nitrotyrosine). These three TRH analogues and five already known ones ([Aad1Tca3]TRH, [D-His2]TRH, [D-Pro3]TRH, [Pro-NH-NH2(3)]TRH and [Tyr2]TRH), were studied in vitro for their binding activity to rat pituitary TRH receptors and a-MSH releasing activity in the neuro-intermediate lobe of frogs. Competition of analogues for 3H-TRH binding to rat anterior pituitary membrane fraction was used. One of ten tested analogues ([Aad1, Tca]3 TRH) was as potent as TRH in competing for high-affinity binding sites (Kd = 8.5 nM). The binding activity of diastereoisomers ([D-His2]TRH and [D-Pro3]TRH) was reduced as well as that of analogue [Pro-NH-NH2(3)]TRH. The rest of the analogues were inactive. The binding activities were in good accordance with alpha-MSH releasing activities.
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PMID:Synthesis, receptor binding affinities and alpha-MSH releasing activities of TRH analogues. 299 54

The aim of this study was to investigate further the influence of dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on the functional activity of the pituitary-adrenocortical system in man. Six normal men were treated with oral metyrapone to stimulate the secretion of ACTH, beta-lipotropin, and beta-endorphin. In these subjects, significant suppression of metyrapone-evoked release of ACTH and related peptides occurred during D infusion (5.5 micrograms/kg X min for 30 min) compared with that during saline infusion. These results indicate that D can induce a significant decline in plasma levels of ACTH, beta-lipotropin, and beta-endorphin, the major circulating peptides from the C-terminal part of proopiocortin, and suggest that opioid peptides may be involved in the control of the functional activity of pituitary-adrenocortical activity in man.
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PMID:Dermorphin reduces the metyrapone-evoked release of adrenocorticotropin, beta-endorphin, and beta-lipotropin in man. 299 56

Modified corticotropin fragment - [Lys11 (Gly)]ACTH-(5-14)- and its cyclic analogue - [cyclo (Glu gamma----epsilon Lys (Gly)] ACTH-(5-14)-undecapeptides have been synthesized by classical approach. The cyclic structure has been fixed by amide bond between gamma-COOH group of glutamic acid and alpha-NH2 group of glycine coupled to the epsilon-NH2 group of lysine. Fragment condensation has been achieved by azide or dicyclohexylcarbodiimide methods. Cyclization has been performed using diphenylphosphorylazide. The melanotropic activity of the cyclicanalogue on isolated frog skin exceeds by two orders of magnitude that of the linear undecapeptide, however the steroidogenic activity in isolated cells of rat adrenal cortex is diminished by an order of magnitude as compared with that of the linear precursor. A similarity of the CD spectra for the cyclic ACTH peptides and their linear counterparts in water and trifluoroethanol points to the similarity and relative rigidity of their structures.
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PMID:[Synthesis of [cyclo(Glu gamma-----epsilon Lys(Gly)]ACTH-(5-14) undecapeptide. Biological and physico-chemical properties of analogs of ACTH-(5-10)- and ACTH-(5-14)-peptides]. 299 4

Reactions of human beta-endorphin, corticotropin and their synthetic analogs with leucine aminopeptidase have been investigated. The results confirmed previous findings that beta-endorphin is resistant to the aminopeptidase action whereas corticotropin is not. Beta-endorphin-(1-5) is completely digested by the enzyme while beta-endorphin-(1-17) is resistant. In contrast, the NH2-terminal 7 residues in corticotropin are removed readily by leucine aminopeptidase. This is confirmed by the observation that human corticotropin-(7-38) is not hydrolyzed by the enzyme. This contrasting behavior of the two hormones toward leucine aminopeptidase may be related to differences in their conformational structures.
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PMID:Distinct behavior of beta-endorphin and corticotropin toward leucine aminopeptidase action. 299 16

ACTH(1-8) and ACTH(9-13)NH2 were used as potential enzyme inhibitors to begin examining the relationship between the acetylation of ACTH- and beta-endorphin-related peptides. ACTH(1-8) was a potent inhibitor of the acetylation of both ACTH- and beta-endorphin-related peptides, whereas ACTH(9-13)NH2 was an effective inhibitor only of the acetylation of ACTH-related substrates. This inhibition pattern indicated that there may be an unusual interaction between some ACTH- and beta-endorphin-related peptides as substrates for the acetyltransferase. Utilizing HPLC to separate ACTH- and beta-endorphin-related peptides present in the same reaction mixture, ACTH(1-14) and beta-endorphin(1-27) at Km and saturating concentrations were used as substrates to examine the ability of one peptide substrate to affect the acetylation of the other. It was observed that the acetylation of ACTH(1-14), even at Km concentration, was relatively unaffected by the presence of beta-endorphin(1-27). However, the acetylation of beta-endorphin(1-27) was significantly reduced by the presence of ACTH(1-14). This preferential acetylation of ACTH-related peptides over the acetylation of beta-endorphin-related peptides might have physiological importance under some conditions.
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PMID:Acetylation of alpha MSH and beta-endorphin by rat neurointermediate pituitary secretory granule-associated acetyltransferase. 299 28


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