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 effects of the infusion of ACTH1-24 and proopiomelanocortin on the denervated adrenal gland have been investigated in conscious 3-6 weeks-old calves by means of the adrenal-clamp technique. To prevent variation in the release of endogenous ACTH the pituitary stalk was cauterized during preparatory surgery. ACTH1-24 (5 ng/min per kg, i.v.) increased the output of cortisol from the adrenal by about 500 ng/min per kg body weight and this effect was rapidly reduced by simultaneous infusion of ovine proopiomelanocortin at 5 ng/min per kg. Release of met5-enkephalin and leu-enkephalin from the adrenal was reduced by ACTH1-24 (P less than 0.05) and this effect was enhanced significantly by additional infusion of proopiomelanocortin (P less than 0.02). However met5-enkephalin represented less than one-third of the met-enkephalin containing peptide released and the output of this pool was unaffected by infusion of ACTH. Proopiomelanocortin had no effect on met5-enkephalin production nor that of the total pool of met5-enkephalin containing peptides. It is concluded that ACTH reduced the quantity of pro-enkephalin processed to met5-enkephalin.
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PMID:Inhibitory effects of proopiomelanocortin on cortical and medullary activity in the calf adrenal. 132 90

Various classes of antidepressant drugs with distinct pharmacologic actions are differentially effective in the treatment of classic melancholic depression--characterized by pathological hyperarousal and atypical depression--associated with lethargy, hypersomnia, and hyperphagia. All antidepressant agents exert their therapeutic efficacy only after prolonged administration. In situ hybridization histochemistry was used to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of 3 different classes of activating antidepressant drugs which tend to be preferentially effective in treating atypical depressions, on the expression of central nervous system genes thought to be dysregulated in major depression. Daily administration (5 mg/kg, i.p.) of the selective 5-hydroxytryptophan (5-HT) reuptake inhibitor fluoxetine, the selective alpha 2-adrenergic receptor antagonist idazoxan, and the nonspecific monoamine oxidase A and B inhibitor phenelzine increased tyrosine hydroxylase mRNA levels by 70-150% in the locus coeruleus after 2 weeks of drug and by 71-115% after 8 weeks. The 3 drugs decreased corticotropin-releasing hormone mRNA levels by 30-48% in the paraventricular nucleus of the hypothalamus. The decreases occurred at 8 weeks but not at 2 weeks. No consistent change in steroid hormone receptor mRNA levels was seen in the hippocampus with the 3 drugs, but fluoxetine and idazoxan increased the level of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNA, respectively, after 8 weeks of drug administration. Proopiomelanocortin (POMC) mRNA levels in the anterior pituitary and plasma adrenocorticotropic-hormone (ACTH) levels were not altered after 2 or 8 weeks of drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin-releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic implications. 135 83

We have determined that greater than or equal to 80% of the Asn-linked oligosaccharides on the glycosylated form of mouse adrenocorticotropin (15-kDa adrenocorticotropin (ACTH)) bear one or more branches terminating with the sequence SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha (S4GGnM). Proopiomelanocortin (POMC), the precursor of ACTH, is the first example of a glycoprotein that is not a member of the glycoprotein hormone family to bear such sulfated structures. Like lutropin and thyrotropin, 15-kDa ACTH bears dibranched oligosaccharides terminating with SO4-4-GalNAc; however, at least half of the oligosaccharides on 15-kDa ACTH terminating with SO4-4-GalNAc consist of more highly branched structures that have not previously been described. Both the GalNAc beta 1,4GlcNAc beta 1,2Man-4-sulfotransferase and the glycoprotein hormone-specific GalNAc-transferase are expressed in the corticotroph-derived AtT-20 cell line. A tripeptide recognition sequence, Pro-Val-Lys, similar to the Pro-Leu-Arg sequence required for recognition of glycoprotein hormone alpha- and beta-subunits by the glycoprotein hormone-specific GalNAc-transferase, is present 8 residues amino-terminal to the glycosylated Asn of 15-kDa ACTH. Thus, POMC has the features expected for specific addition of the S4GGnM sequence to its oligosaccharides. The recent discovery of a receptor in hepatic endothelial cells that recognizes oligosaccharides terminating with S4GGnM suggests these sulfated oligosaccharides will regulate the circulatory half-life of glycosylated POMC cleavage products.
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PMID:Pro-opiomelanocortin synthesized by corticotrophs bears asparagine-linked oligosaccharides terminating with SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha. 161 97

The intermediate lobe of the pituitary is composed of a homogeneous population of endocrine cells, the melanotrophs, which secrete several bioactive peptides including alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin. In contrast to most endocrine glands which are richly vascularized, the intermediate lobe of the pituitary contains very few blood vessels; in some species, the pars intermedia is virtually totally avascular. In contrast, pituitary melanotrophs are richly supplied by nerve fibers originating from the hypothalamus. The pars intermedia thus appears as a pure model of neuroendocrine communication, i.e. it is an archetype of the mode of transducing interface between the central nervous system and endocrine effectors. In mammalian species, different types of nerve terminals containing dopamine, norepinephrine, gamma-aminobutyric acid (GABA) and serotonin have been identified. In lower vertebrates, particularly in fish and amphibians, the pars intermedia is also innervated by peptidergic fibers which are though to take part in regulation of the secretory activity of the melanotroph. In these animals, the pars intermedia is regarded as a major center of neuroendocrine integration and an exceptional model to investigate the process of communication between the brain and the endocrine glands. The purpose of the present review is to summarize our current knowledge on the synthesis, processing and release of peptide hormones from pars intermedia cells and to survey the multiple regulatory mechanisms which are involved in the control of the activity of pituitary melanotrophs. Proopiomelanocortin, a multifunctional precursor. Pituitary melanotrophs synthetise a major precursor protein called proopiomelanocortin (POMC) which generates through proteolytic cleavage several biologically active peptides including adrenocorticotropic hormone (ACTH), endorphins and MSHs. In lower vertebrates, alpha-MSH is generally considered as the major hormone secreted by melanotrophs, in that it is involved in the process of skin colour adaptation. The post-translational processing of POMC, which yields to the mature hormones released by melanotrophs, includes a number of steps: glycosylation, phosphorylation, tissue-specific proteolytic cleavage, amidation and acetylation. Some of these posttranslational modifications can be regulated by neuroendocrine factors. For instance, in frogs, it has been shown that dopamine inhibits acetylation of alpha-MSH and thus reduces the secretion of the biologically active form of the peptide. The intermediate lobe of the pituitary: a model of neuroendocrine integration. In most vertebrate species, the intermediate lobe of the pituitary is innervated by catecholamine-containing fibers. In particular, the presence of dopaminergic nerve fibers has been observed in the pars intermedia of mammals and poikilotherms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The intermediate lobe of the pituitary, model of neuroendocrine communication]. 171 55

Proopiomelanocortin (POMC) is a polyprotein which is targeted to the regulated secretory pathway of neuroendocrine cells where it undergoes tissue-specific proteolysis to yield peptides such as adrenocorticotropic hormone, beta-lipotropin and beta-endorphin. The pro-region of POMC is 49 amino acid long with two disulfide bonds between cysteine residues 2 and 24 and 8 and 20. These cysteine residues are conserved across the species. The pro-region contains no known hormonal sequence. Sorting to the regulated secretory pathway is thought to involve targeting signals encoded in the structure of secretory proteins. In the present study, we have examined the possibility that the disulfide bridges located in the NH2-terminal portion of the pro-region of POMC are essential for maintaining a determinant involved in the sorting of POMC to the regulated secretory pathway. Using site-directed and deletion mutagenesis of the porcine POMC cDNA, we created mutants in which one or both disulfide bridges were disrupted or in which the first 26 amino acid residues of the pro-region were deleted. Recombinant retroviruses carrying the mutated POMC cDNAs were used to infect Neuro2A cells. Immunofluorescence and immunoelectron microscopy studies performed on infected cells revealed that the unmutated and mutated POMC-immunoreactive peptides were localized in dense-core vesicles at the tips of cellular extensions. Analysis of the POMC-immunoreactive peptides extracted from the infected Neuro2A cells indicated that the mutated precursors in which one disulfide bridge was disrupted (POMC-S2 or POMC-S8) were stored and processed as efficiently as the unmutated POMC. By contrast, the mutated precursor in which both disulfide bridges were disrupted (POMC-S2,8) did not accumulate in intracellular compartments to the same extent as unmutated POMC. Moreover, this mutant was very inefficiently processed and no release could be observed upon stimulation of the cells with K+/Ca2+. These results suggest that POMC-S2,8 entered the regulated secretory pathway less efficiently than the unmutated precursor. However, when both disulfide bridges were removed from the precursor from the precursor by deletion of the first 26 amino acid residues of POMC, the truncated precursor (POMC delta 1-26) behaved as the unmutated POMC. Taken together our results indicate that the NH2-terminal portion of the pro-region including both disulfide bridges can be deleted without affecting the targeting of the molecule to secretory granules. However, when the entire POMC sequence is expressed in Neuro2A cells, the proper folding of the NH2-terminal region might be important for efficient processing and targeting.
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PMID:Investigation of a possible role of the amino-terminal pro-region of proopiomelanocortin in its processing and targeting to secretory granules. 179 12

Most peptide hormones and neurotransmitters are synthesized as larger precursor proteins, which are post-translationally processed to mature bioactive products. An early event in prohormone maturation is endoproteolytic cleavage, occurring usually at pairs of basic amino acids (e.g. Lys-Arg). Since many of the characteristics of a prohormone endoprotease are unknown, distinguishing these enzymes from other cellular proteases in vitro has been difficult. In this report, the substrate specificity of a model prohormone processing system, the insulinoma cell line Rin m5F, was characterized in vivo to establish a set of criteria by which putative proinsulin endoproteases may be assessed. To determine the role of composition of the paired basic amino acid site in directing cleavage, a series of mutant prohormones containing altered cleavage sites was constructed and expressed in Rin m5F cells. Proopiomelanocortin (POMC) was used as a substrate since this prohormone was previously shown to be processed by these cells. To control for positional effects, all four permutations of lysine and arginine (Lys-Arg, Arg-Arg, Arg-Lys, and Lys-Lys) were introduced at both the efficiently processed cleavage site separating the ACTH and beta-lipotropin (beta-LPH) domains of POMC and at the inefficiently processed site in the beta-endorphin sequence near the COOH-terminus of the precursor. His-Arg and Met-Arg sites were also introduced at the ACTH/beta-LPH junction to assess the requirement for paired lysines and arginines. Identification of POMC-derived peptides demonstrated efficient processing of Lys-Arg and inefficient processing of Lys-Lys and Arg-Lys sites at both positions in the prohormone. The Arg-Arg sequence, however, was processed in a position-dependent manner, being efficiently cleaved between ACTH and beta-LPH but only about 50% processed within beta-endorphin. His-Arg was not cleaved in Rin m5F cells, although surprisingly Met-Arg was partially processed. These results indicate a strict preference of the insulinoma prohormone endoprotease(s) for paired basic amino acids ending in arginine, but that processing efficiency of some sequences may be modulated by location within the precursor molecule.
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PMID:An in vivo characterization of the cleavage site specificity of the insulin cell prohormone processing enzymes. 216 Apr 59

It is now well-known that the plasmatic levels of beta-endorphin (B-Ep) in subjects suffering from hyperphagie obesity during childhood, adolescence and adult age, are higher than those of normal weight standard-wright. The causes are still unknown. In obese subjects, there is also a dissociation between plasmatic levels of B-Ep and of ACTH, in spite of the common origin of Proopiomelanocortin (POMC). On the basis of these observations we studied the plasmatic levels of B-Ep, ACTH and cortisol, basal and after DXM, before and after the reduction of body weight. With the aim of evaluating pharmacological interference, the obese subjects were treated with diet alone or diet associated with an anorectic and serotoninergic drug (fenfluramin). The results have shown that after slimming, obtained with diet alone or with the help of the serotoninergic drug, the hyperendorphinemia persists both in basal conditions and after the DXM test. The verification of such behaviour in some psychiatric diseases supports our assumption of a link between hyperendorphinemia, behaviour alterations, hyperphagy and obesity.
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PMID:[Plasma levels of beta-endorphin , ACTH and cortisol in obese patients subjected to several weight-loss treatments]. 216 28

Proopiomelanocortin is a polypeptide precursor molecule, the processing of which generates ACTH, beta-endorphin, the beta- and gamma-lipotropins, the joining peptide, and the NH2-terminal fragment. Anterior pituitary corticotrophs are the major site of proopiomelanocortin gene expression in man and the predominant, if not sole source of circulating ACTH. Recent data have established that proopiomelanocortin gene expression also occurs in various normal nonpituitary tissues, one of the best studied being the testis. In this latter organ the dominant gene products are short transcripts of approximately 800 nucleotides, which lack the first two exons of the gene and cannot encode a complete proopiomelanocortin molecule. In this report we show that the mode of proopiomelanocortin gene expression is occasionally modified in human Leydig cell tumors: a 1,200-nucleotide mRNA species identical to that in the pituitary is produced. It results from the usual (pituitary) start site of transcription and thus can encode the complete proopiomelanocortin molecule. In two out of six tumors, large amounts of the 1,200-nucleotide transcript led to a dramatic increase of approximately 1,000-fold in proopiomelanocortin peptide concentrations as compared with the normal and peritumoral testis. Proopiomelanocortin processing in these tumors generates various peptide fragments including ACTH. These results may help to understand the mechanism of proopiomelanocortin expression in nonpituitary tumors and have implications for the more general phenomenon of ectopic hormone secretion.
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PMID:Pituitary-like proopiomelanocortin transcripts in human Leydig cell tumors. 239 36

Proopiomelanocortin and its derivative peptides alpha MSH and beta-endorphin are produced by Leydig cells. beta-Endorphin or another testicular opiate is believed to suppress Sertoli cell hypertrophy. The goal of this study was to determine the effects of another proopiomelanocortin-derived peptide on Sertoli cells. The activities of both alpha MSH and des-acetyl alpha MSH have been compared, since this latter peptide has been identified in testicular extracts. Both alpha MSH and des-acetyl alpha MSH stimulated cAMP accumulation in the media of primary Sertoli cell cultures when incubated in the presence of a phosphodiesterase inhibitor, FSH or forskolin. Both peptides shifted the FSH dose-response curve to the left, making the cells more sensitive to this gonadotropin. The apparent potencies of alpha MSH and its des-acetyl derivative, as measured in Sertoli cells, were similar. We conclude that the MSHs are one of a group of modulators regulating Sertoli cells via the cAMP system, and Sertoli cells are equally responsive to alpha MSH and des-acetyl alpha MSH, unlike central nervous system and melanocytes which show differential responses to these peptides.
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PMID:Stimulation of adenosine 3',5'-monophosphate production in rat Sertoli cells by alpha-melanotropin-stimulating hormone (alpha MSH) and des-acetyl alpha MSH. 241 22

Proopiomelanocortin (POMC), a precursor protein for ACTH, beta-endorphin, and the MSHs, has been identified in the reproductive tracts of both male and female. With rat pituitary POMC complementary DNA (cDNA) as a hybridization probe, POMC-like messenger RNA (mRNA) was identified in the ovaries of rat, mouse, and monkey. The molecular size of POMC-like mRNA in the ovary was 150-200 bases smaller than in the pituitary and hypothalamus but identical to that in the testis and epididymis. The size heterogeneity of POMC mRNA observed in various tissues is not due to differences in the lengths of the poly(A) tail, as measured by RNase H digestion. S1 nuclease mapping analysis revealed that POMC mRNAs isolated from pituitary, testis, or ovary share the nucleotide sequences coding for ACTH, beta-lipotropin, and the 3'-untranslated region. The regulation of ovarian POMC-like mRNA was also investigated. Treatment of 25-day-old immature female rats with PMSG resulted in profound increases in the ovarian content of total RNA, poly(A) RNA, and POMC-like mRNA. The concentration of ovarian POMC-like mRNA during pregnancy increased increased to 3-4 times that in immature or normally cycling animals. POMC-derived peptides are present in the human placenta and are synthesized de novo in cultured placental cells. In this report we also demonstrate POMC-like mRNA in the placenta of rat, mouse, and human. The size of POMC-like mRNA in the placenta was similar to that observed in the testis, epididymis, and ovary and different from that found in the pituitary or hypothalamus. The concentration of placental POMC-like mRNA did not change throughout pregnancy. In conclusion, we have demonstrated that 1) POMC-like mRNA is present in the ovary and placenta of rodents and primates; 2) the size of POMC-like mRNA in the ovary and placenta, like that in the testis and epididymis, is smaller than that in the pituitary and hypothalamus, probably owing to a shortening of the 5'-ends; and 3) the expression of this gene is regulated by gonadotropins in the ovary but probably not in the placenta.
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PMID:Expression and regulation of proopiomelanocortin-like gene in the ovary and placenta: comparison with the testis. 242 19


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