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Strategies in the Regulation of Secretory Signals from Proopiomelanocortin-Producing Cells

  • Bruce G. Jenks
  • Hans J. Leenders
  • B. M. Lidy Verburg-van Kemenade
  • Marie-Christine Tonon
  • Hubert Vaudry
Part of the Biochemical Endocrinology book series (BIOEND)

Summary

Proteolytic cleavage of the precursor protein proopiomelanocortin (POMC) has the potential to yield a number of different bioactive peptides. The current status of the possible control points in regulating the bioactive output of POMC-producing cells is considered in this review. Attention is payed to a possible role of glycosylation of POMC in directing the cleavage process but we conclude there is insufficient evidence to support this hypothesis. Detailed attention is also given to the regulatory role of the N-terminal acetylation of two of the POMC-derived peptides, α-melanotropin and β-endorphin. In particular, the possibility is considered that the acetylation process within a POMC-cell could be regulated and thus used to modulate the secretory signal of the cell.

Keywords

Secretory Signal Intermediate Lobe Rana Ridibunda Acetylation Process Neurointermediate Lobe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Barnea, A., and Cho, G,, 1983, Acetylation of adrenocorticotropin and β-endorphin by hypothalamic and pituitary acetyltransferases, Neuroendocrinology, 37:434.PubMedCrossRefGoogle Scholar
  2. Benett, H. P. J., Lowry, P. J., Mc Marten, C., and Scott, A. P., 1974, Structural studies of alpha-melanocyte stimulating hormone and a novel beta-melanocyte stimulating hormone from the neurointer-mediate lobe of the pituitary of the dogfish, Squalus acanthias, Biochem. J., 141:439.Google Scholar
  3. Bennett, H. P. J., Browne, C. A., and Solomon S., 1981, Biosynthesis of phosphorylated forms of corticotropin-related peptides, Proc. Natl. Acad. Sci. USA, 78:4713.PubMedCrossRefGoogle Scholar
  4. Bennett, H. P. J., Browne, C. A., and Solomon S., 1982, Characterization of eight forms of corticotropin-like intermediate lobe peptide from the rat intermediate pituitary, J. Biol. Chem., 257:10096.PubMedGoogle Scholar
  5. Birnberg, N. C., Lissitzky, J. C., Hinman, M., and Herbert. E., 1983, Glucocorticoids regulate proopiomelanocortin gene expression in vivo at the level of transcription and secretion, Proc. Natl. Acad. Sci. USA, 80:6982.PubMedCrossRefGoogle Scholar
  6. Bourbonnais, Y., and Crine, P., 1985, Post-translational incorporation of [35S] sulfate into oligosaccharide side chains of pro-opiomelanocortin in rat intermediate lobe cells. J. Biol. Chem., 260:5832.PubMedGoogle Scholar
  7. Burdarf, M. L., and Herbert, H., 1982, Effect of tunicamycin on the synthesis, processing and secretion of pro-opiomelanocortin peptides in mouse pituitary cells, J. Biol. Chem., 257:10135.Google Scholar
  8. Chang, T. L., and Loh, Y. P., 1984, In vitro processing of proopiocortin by membrane-associated and soluble converting enzyme activities from rat intermediate lobe secretory granules, Endocrinology, 114: 2092.PubMedCrossRefGoogle Scholar
  9. Chappell, M. C., Loh, Y. P., and O’Donohue, T. L., 1982, Evidence for an opiomelanotropin acetyltransferase in the rat pituitary intermediate lobe, Peptides, 3:405.PubMedCrossRefGoogle Scholar
  10. Chen, C. L. C., Dionne, F. T., and Roberts, J. L., 1983, Regulation of pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds, Proc. Natl. Acad. Sci. USA, 80:2211.PubMedCrossRefGoogle Scholar
  11. Chen, C. L. C., Mather, J. P., Morris, P. L., and Bardin, C. W., 1984, Expression of pro-opiomelanocortin-like gene in the testis and epididymis, Proc. Natl. Acad. Sci. USA, 81:5672.PubMedCrossRefGoogle Scholar
  12. Chrétien, M., and Seidah, N. G., 1981, Chemistry and biosynthesis of proopiomelanocortin, Mol. Cell. Biochem., 34:101.PubMedCrossRefGoogle Scholar
  13. Drouin, J., and Goodman, H. M., 1980, Most of the coding region of rat ACTH/β-LPH precursor gene lacks intervening sequences, Nature, 288: 610.PubMedCrossRefGoogle Scholar
  14. Eipper, B. A., and Mains, R. E., 1980, Structure and biosynthesis of proadrenocoticotropin/endorphin and related peptides, Endocrine Reviews, 1:1.PubMedCrossRefGoogle Scholar
  15. Eipper, B. A., and Mains, R. E., 1982, Phosphorylation of pro-adrenocorticotropin-endorphin-derived peptides. J. Biol. Chem., 257:4907.PubMedGoogle Scholar
  16. Eipper, B. A., Glembotski, C. C., and Mains, R. E., 1983a, Selective loss of α-melanotropin-amidating activity in primary cultures of rat intermediate pituitary cells, J. Biol. Chem., 258:7292.PubMedGoogle Scholar
  17. Eipper, B. A., Glembotski, C. C., and Mains, R. E., 1983b, Bovine intermediate pituitary α-amidation enzyme: preliminary characterization, Peptides, 4:921.PubMedCrossRefGoogle Scholar
  18. Emeson, R. B., 1984, Hypothalamic peptidylglycine α-amidation monooxygenase: preliminary characterization, J. Neurosci., 4:2604.PubMedGoogle Scholar
  19. Estivariz, F. E., Iturriza, F., Mc Lean, C., Hope, J., and Louwry, P. J., 1982, Stimulation of adrenal mitogenesis by N-terminal proopiocortin peptides, Nature, 297:419.PubMedCrossRefGoogle Scholar
  20. Evans, C. J., Erdelyi, E., Weber, E., and Barchas, J. D., 1983, Identification of pro-opiomelanocortin-derived peptides in the human adrenal medulla, Science, 221:957.PubMedCrossRefGoogle Scholar
  21. Farese, R. V., Ling, N. C., Sabir, M. A., Larson, R. E., and Trudeau, W. L., 1983, Comparison of effects of adrenocorticotropin and Lys-γ3-melanocyte stimulating hormone on steroidogenesis, adenosine 3′,5′-monophosphate production, and phospholipid metabolism in rat adrenal fasciculata reticularis cells in vitro, Endocrinology, 112: 129.PubMedCrossRefGoogle Scholar
  22. Glembotski, C. C., 1982, Characterization of the peptide acetyltransferase activity in bovine and rat intermediate pituitaries responsible for the acetylation of β-endorphin and α-melanotropin. J. Biol. Chem., 257:10501.PubMedGoogle Scholar
  23. Grube, D., Voigt, K. A., Weber, E., 1978, Pancreatic glucagon cells contain endorphin-like immunoreactivity, Histochemistry, 59:75.PubMedCrossRefGoogle Scholar
  24. Guy, J. Leclerc, R., Vaudry, H., and Pelletier, G., 1980, Identification of a second category of α-melanocyte-stimulating hormone (α-MSH) neurons in the rat hypothalamus, Brain Res., 199:135.PubMedCrossRefGoogle Scholar
  25. Guy, J., Vaudry, H., and Pelletier, G., 1981, Differential projections of two immunoreactive α-melanocyte stimulating hormone (α-MSH) neuronal systems in the rat brain, Brain Res., 220:199.PubMedCrossRefGoogle Scholar
  26. Guy, J., Vaudry, H., and Pelletier, G., 1982, Further studies on the identification of neurons containing immunoreactive alpha-melanocyte stimulating hormone (α-MSH) in the rat brain. Brain Res., 239: 265.PubMedCrossRefGoogle Scholar
  27. Ham, J., Mc Farthing, K. G., Toogood, C. I. A., and Smyth, D. G., 1984a, Influence of dopaminergic agents on β-endorphin processing in rat pars intermedia, Biochem. Soc. Transact., 12:927.Google Scholar
  28. Ham, J., and Smyth, D. G., 1984b, Regulation of bioactive β-endorphin processing in rat pars intermedia, Febs Lett., 75:407.CrossRefGoogle Scholar
  29. Holt, V., Haarmann, I., Slizinger, B. R., and Herz, A., 1982, Chronic haloperidol treatment increases the level of in vitro translatable m-RNA coding for β-endorphin/ACTH precursor POMC in the pars intermedia of the rat, Endocrinology, 110:1885.CrossRefGoogle Scholar
  30. Hoshina, H., Hortin, G., and Boime, I., 1982, Rat pro-opiomelanocortin contains sulphate, Science, 217:63.PubMedCrossRefGoogle Scholar
  31. Herbert, E., 1981, Discovery of pro-opiomelanocortin, a cellular polyprotein, Trends Biochem. Sci., 6:184.CrossRefGoogle Scholar
  32. Jégou, S., Tonon, M.C., Guy, J., Vaudry, H., and Pelletier, G., 1983, Biological and immunological characterization of α-melanocyte-stimulating hormone (α-MSH) in two neuronal systems of the rat brain, Brain Res., 260:91.PubMedCrossRefGoogle Scholar
  33. Jenks, B. G., Cruijsen, P. M. J. M., Feyen, J. H. M., Martens, G. J. M., and van Overbeeke, A. P., 1983a, Effects of tumicamycin on biosynthesis of pars intermedia peptides in the mouse, in: “Integrative Neurohumoral Mechanisms: Physiological and Clinical Aspect”, Hungaria Academic press, Budapest pp 281–287.Google Scholar
  34. Jenks, B. G., van Daal, J. H. H. N., Scharenberg, J. G. M., Martens, G. J. M., and van Overbeeke, A. P., 1983b, Biosynthesis of pro opiomelanocortin-derived peptides in the mouse neurointermediate lobe, J. Endocrinol., 98:19.PubMedCrossRefGoogle Scholar
  35. Jenks, B. G., Verburg van Kemenade, B. M. L., Tonon, M. C., and Vaudry, H., 1985, Regulation of biosynthesis and release of pars intermedia peptides in Rana ridibunda: dopamine affects both acetylation and release of α-MSH. Peptides, in press.Google Scholar
  36. Jenks, B. G., Ederveen, A. G. H., Freyen, J. H. M., van Overbeeke, A. P., 1986, The functional significance of glycosylation of proopiomelanocortin in melanotrophs of the mouse pituitary gland, J. Endocrinol., in press.Google Scholar
  37. Kawauchi, H., Adachi, Y., and Tsubokawa, M., 1980, Occurence of a new melanocyte stimulating hormone in the salmon pituitary gland, Biochem. Biophys. Res. Commun., 96:1508.PubMedCrossRefGoogle Scholar
  38. Larsson, L. I., 1981, Adrenocorticotropin-like and α-melanotropin-like peptides in a subpopulation of human gastrin cell granules: Bioassay, immunoassay and immunocytochemical evidence, Proc. Natl. Acad. Sci. USA, 78:2990.PubMedCrossRefGoogle Scholar
  39. Leboulenger, F., Lihrmann, I., Netchitailo, P., Delarue, C., Perroteau, I., Ling, N., and Vaudry, H., 1986, In vitro study of frog (Rana ridibunda Pallas) interrenal function by use of a simplified perifusion system. VIII. Structure-activity relashionship of synthetic ACTH fragments and γ-MSH, Gen. Comp. Endocrinol., in press.Google Scholar
  40. Leenders, H. J., Janssens, J. J. W., Theunissen, H. J. M., Jenks, B.G., and van Overbeeke, A. P., 1986, Acetylation of melanocyte stimulating hormone and β-endorphin in the pars intermedia of the perinatal pituitary gland in the mouse. Neuroendocrinology, in press.Google Scholar
  41. Ling, N., Ying, S., Minick, S., and Guillemin, R., 1979, Synthesis and biological activity of four γ-melanotropin peptides derived from the cryptic region of the adrenocorticotropin β-lipotropin precursor, Life Sci. 25:1773.PubMedCrossRefGoogle Scholar
  42. Liotta, A. S., and Krieger, D. T., 1980, In vitro biosynthesis and comparative posttranslational processing of immunoreactive precursor corticotropin/β-endorphin by human placentral and pituitary cells, Endocrinology, 106:1504.PubMedCrossRefGoogle Scholar
  43. Loh, Y. P., and Gainer, H., 1978, The role of glycosylation on the biosynthesis, degradation and secretion of ACTH-β-lipotropin common precursor and its peptide products, Febs Lett., 96:269.PubMedCrossRefGoogle Scholar
  44. Loh, Y. P., and Gainer, H., 1979, The role of the carbohydrate in the stabilization, processing, and packaging of the glycosylated adrenocorticotropin-endorphin common precursor in toad pituitaries. Endoccrinology, 105:474.CrossRefGoogle Scholar
  45. Loh, Y. P., and Jenks, B. G., 1981, Evidence for two different pools of adrenocorticotropin, α-melanocyte stimulating hormone, and endorphin-related peptides released by the frog pituitary neurointermediate lobe. Endocrinology, 109:54.PubMedCrossRefGoogle Scholar
  46. Loh, Y. P., and Chang, T. L., 1982, Pro-opiocortin converting activity in rat intermediate and neural lobe secretory granules, Febs Lett., 137:57.PubMedCrossRefGoogle Scholar
  47. Mains, R. E., and Eipper, B. A., 1983, Phosphorylation of rat and human adrenocorticotropin-related peptides: physiological regulation and studies of secretion, Endocrinology, 112:1986.PubMedCrossRefGoogle Scholar
  48. Margioris, A., Liotta, A. S., Vaudry, H., Bardin, C. W., and Krieger, D. T., 1983, Characterization of immunoreactive proopiomelanocortin related peptides in rat testis, Endocrinology, 113:663.PubMedCrossRefGoogle Scholar
  49. Martens, G. J. M., Jenks, B. G., and van Overbeeke, A. P., 1981, Nα-acetylation is linked to α-MSH release from pars intermedia of the amphibian pituitary gland, Nature, 294:558.PubMedCrossRefGoogle Scholar
  50. Millington, W. R., Chappell, M. C., and O’Donohue, T. L., 1985, Induction of opiomelanocortin acetyltransferase activity in the pars intermedia of rat pituitary, 67th Ann. Meet. Endocrine Society, Abst. 651.Google Scholar
  51. O’Donohue, T. L., and Dorsa, D. M., 1982, The opiomelanotropinergic neuronal and endocrine system, Peptides, 3:353.PubMedCrossRefGoogle Scholar
  52. Pedersen, R. C., and Brownie, A. C., 1980, Adrenocortical response to corticotropin is potentiated by part of the ami no-terminal region of pro-corticotropin/endorphin, Proc. Natl. Acad. Sci. USA, 77: 2239.PubMedCrossRefGoogle Scholar
  53. Pelaprat, D., Seidah, N. G., Sikstrom, R.A., Lambelin, P., Hamelin, J., Lazure, C., Cromlish, J. A., and Chrétien, M., 1984, Subcellular fractionation of pituitary neurointermediate lobes: revelation of various basic proteases, Endocrinology, 115:581.PubMedCrossRefGoogle Scholar
  54. Phillips, M. A., Budarf, M. L., and Herbert, E., 1981, Glycosylation events in the processing and secretion of pro-ACTH-endorphin in mouse pituitary tumor cells, Biochemistry, 20:1666.PubMedCrossRefGoogle Scholar
  55. Randle, J. C. R., Moor, B. C., and Kraicer, J., 1983, Differential control of the release of proopiocortin-derived peptides from the pars intermedia of the rat pituitary, Neuroendocrinology, 37:131.PubMedCrossRefGoogle Scholar
  56. Roberts, J. L., Eberwine, H., and Gee, C. E., 1983, Analysis of POMC gene expression by transcription assay and in situ hybridization histo-chemistry, in: “Cold Spring Harbor Symposia on Quantitative Biology” Vol. 28 pp 385–391.CrossRefGoogle Scholar
  57. Rosenfeld, M. G., Mermod, J. J., Amara, S. G., Swanson, L. W., Sawchenko, P. E., Rivier, J., Vale, W., and Evans, R. M., 1983, Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing, Nature, 304:129.PubMedCrossRefGoogle Scholar
  58. Saito, E., and Odell, W. D., 1983, Corticotropin/lipotropin common precursor-like material in normal rat extrapituitary tissues. Proc. Natl. Acad. Sci. USA, 80:3792.PubMedCrossRefGoogle Scholar
  59. Schachter, B. S., Johnson, L. K., Baxter, J. D., and Roberts, J. L., 1982, Differential regulation by glucocorticoids of proopiomelanocortin mRNA levels in the anterior and intermediate lobes of the rat pituitary, Endocrinology, 106:1442.CrossRefGoogle Scholar
  60. Seidah, N. G., Pélaprat, D., Rochemont, J., Lambelin, P., Dennis, M., Chan, J. S. D., Hamelin, J., Lazure, C., and Chrétien, M., 1983, Enzymatic maturation of pro-opiomelanocortin by anterior pituitary granules, J. Chromatogr., 266:213.PubMedCrossRefGoogle Scholar
  61. Stoeckel, M. E., Schmitt, G., and Porte, A., 1981, Fine structure and cytochemistry of the mammalian pars intermedia, in “Peptides of the Pars Intermedia”, Ciba Foundation Symposium, Pitman Medical, pp 101-127.Google Scholar
  62. Takahaski, A., Kubota, J., Kawanchi, H., and Hirano, T., 1985, Effects of N-terminal peptide of salmon proopiocortin on interrenal function of the rainbow trout, Gen. Comp. Endocrinol., 58:328.CrossRefGoogle Scholar
  63. Uhler, M., and Herbert, E., 1983, Complete amino acid sequence of mouse pro-opiomelanocortin derived from the nucleotide sequence of proopiomelanocortin cDNA, J. Biol. Chem., 258:257.PubMedGoogle Scholar
  64. Vaudry, H., Jenks, B. G., and van Overbeeke, A. P., 1983, The frog pars intermedia contains only the non-acetylated form of α-MSH: acetylation to generate α-MSH occurs during the release process, Life Sci., 33:97.PubMedCrossRefGoogle Scholar
  65. Vaudry, H., Jenks, B. G., and Overbeeke, A. P., 1984, Biosynthesis, processing and release of pro-opiomelanocortin related peptides in the intermediate lobe of the pituitary gland of the frog (Rana ridibunda), Peptides, 5:905.PubMedCrossRefGoogle Scholar
  66. Vaudry, H., Jenks, B. G., Verburg-van Kemenade, B. M. L., and Tonon, M.C., 1986, Effect of tunicamycin on biosynthesis, processing and release of proopiomelanocortin-derived peptides in the intermediate lobe of the frog Rana ridibunda, submitted.Google Scholar
  67. Watkins, W. B., Bruni, J. F., and Yen, S. S. C., 1980, β-endorphin and somatostatin in the pancreatic D-cell; colocalization by immunocytochemistry, J. Histochem. Cytochem., 28:1170.PubMedCrossRefGoogle Scholar
  68. Watson, S. J., Akil, H., Richard, C. W., and Barchas, J. D., 1978, Evidence for two separate opiate peptide neuronal systems and the coexistence of β-lipotropin, β-endorphins and ACTH immunoreactivities in the same hypothalamic neurons, Nature, 275:226.PubMedCrossRefGoogle Scholar
  69. Watson, S. J., and Akil, H., 1979, The presence of two α-MSH positive cell groups in the rat hypothalamus, Europ. J. Pharmacol., 48:101.CrossRefGoogle Scholar
  70. Watson, S. J., and Akil, H., 1980, α-MSH in rat brain: occurence within and outside of β-endorphin neurons, Brain Res., 182:217.PubMedCrossRefGoogle Scholar
  71. Wolter, H. J., 1985, α-melanotropin, β-endorphin and adrenocorticotropin-like immunoreactivities are colocalized within duodenal myenteric plexus perikarya, Brain Res., 325:290.PubMedCrossRefGoogle Scholar
  72. Zakarian, S., and Smyth, D. G., 1979, Distribution of active and inactive forms of endorphins in rat pituitary and brain, Proc. Natl. Acad. Sci. USA, 76:5972.PubMedCrossRefGoogle Scholar
  73. Zakarian, S., and Smyth, D. G., 1982, β-endorphin is processed differently in specific regions of rat pituitary and brain, Nature, 296:250.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Bruce G. Jenks
    • 1
  • Hans J. Leenders
    • 1
  • B. M. Lidy Verburg-van Kemenade
    • 1
  • Marie-Christine Tonon
    • 2
  • Hubert Vaudry
    • 2
  1. 1.Department of ZoologyCatholic University, ToernooiveldNijmegenThe Netherlands
  2. 2.Laboratory of Molecular Endocrinology, UA CNRS 650, Faculty of SciencesUniversity of RouenMont-Saint-AignanFrance

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