The Neurophysins and Small Cell Lung Cancer

  • William G. North
  • L. Herbert Maurer
  • Joseph F. O’Donnell
Part of the Cancer Treatment and Research book series (CTAR, volume 11)


Neurophysins are single chain proteins of about 10,000 daltons in size that are normally produced by neurons in the hypothalamus. These proteins are rich in cysteine, glycine, and glutamic acid, and all of those so-far studied have an N-terminal alanine. Most of the neurons that produce neurophysins are located in the supraoptic and paraventricular nuclei of the anterior hypothalamus. Two other well-characterized products of these neurons are the hormones oxytocin and vasopressin (antidiuretic hormone, ADH).


Small Cell Carcinoma Hypothalamic Neuron Neurosecretory Granule Neural Lobe Small Cell Tumor 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sachs H, Fawcett P, Takabatake Y, Portanova R: Biosynthesis and release of vasopressin and neurophysin. Rec Prog Horm Res 25:447–491, 1969.PubMedGoogle Scholar
  2. 2.
    Pickering BT, Jones CW, Burford GD, McPherson M, Swann RR, Heap PF, Morris JF: The role of neurophysin proteins: suggestions from the study of their transport and turnover. Ann NY Acad Sci 248: 15–35, 1975.PubMedCrossRefGoogle Scholar
  3. 3.
    Gainer H, Same Y, Brownstein MJ: Biosynthesis and axonal transport of rat neurohypophysial proteins and peptides. J Cell Biol 73: 366–381, 1977.PubMedCrossRefGoogle Scholar
  4. 4.
    North WG, LaRochelle FT Jr, Morris JF, Sokol HW, Valtin H: Biosynthetic specificity of neurons producing neurohypophysial principles. In: Current Studies of Hypothalamic Function. Lederis K, Veale WH (eds)., Basel: Karger, 1978, pp 62–76.Google Scholar
  5. 5.
    Russell JT, Brownstein MJ, Gainer H: Trypsin liberates an arginine vasopressin-like peptide and neurophysin from a Mt 20,000 putative common precursor. Proc Natl Acad Sci 76: 6086–6090, 1979.PubMedCrossRefGoogle Scholar
  6. 6.
    Pickering BT, North WG: Biochemical and functional aspects of magnocellular neurons and hypothalamic diabetes insipidus. Ann NY Acad Sci, 1982 (in press).Google Scholar
  7. 7.
    Land H, Schutz G, Schmale H, Richter D: Nucleotide sequence of cloned DNA encoding bovine arginine vasopressin-neurophysin II precursor. Nature 295: 299–303, 1982.PubMedCrossRefGoogle Scholar
  8. 8.
    Robinson AG, Haluszczak C, Wilkins JA, Heullmantel AB, Watson CG: Physiological control of two neurophysins in humans. J Clin Endocrinol Metab 44: 330, 1977.PubMedCrossRefGoogle Scholar
  9. 9.
    North WG, LaRochelle FT Jr, Melton J, Mills RC: Isolation and partial characterization of two human neurophysins: Their use in the development of specific radioimmunoassays. J Clin Endocrinol Metab 51: 884–891, 1980.PubMedCrossRefGoogle Scholar
  10. 10.
    Valtin H, Sokol HW (eds): NY Acad Sci ‘The Brattleboro Rat’, 1982, vol. 394.Google Scholar
  11. 11.
    Russell JT, Brownstein MJ, Gainer H: Time course of appearance and release of [35S]cysteine labelled neurophysins and peptides in the neurohypophysis. Brain Research 205: 299–311, 1981.PubMedCrossRefGoogle Scholar
  12. 12.
    Schmale H, Leipold B, Richter D: Cell-free translation of bovine hypothalamic mRNA. FEBS Letters 108: 311–316, 1979.PubMedCrossRefGoogle Scholar
  13. 13.
    Schmale H, Richter D: Immunological identification of a common precursor to arginine vasopressin and neurophysin II synthesized by in vitro translation of bovine hypothalamic mRNA. Proc Natl Acad Sci 78: 766–769, 1981.PubMedCrossRefGoogle Scholar
  14. 14.
    Guidice LC, Chaiken IM: Immunological and chemical identification of a neurophysin-containing protein coded by messenger RNA from bovine hypothalamus. Proc Natl Acad Sci 76: 3800–3804, 1979.CrossRefGoogle Scholar
  15. 15.
    Lin C, Joseph-Bravo P, Sherman T, McKelvy J: Cell-free synthesis of putative neurophysin precursors from rat and mouse hypothalamic poly (A)-RNA. Biochem Biophys Res Commun 89: 943–950, 1979.PubMedCrossRefGoogle Scholar
  16. 16.
    Russell JT, Brownstein MJ, Gainer H: Biosynthesis of vasopressin, oxytocin and neurophysins: Isolation and characterization of two common precursors (propressophysin and pro-oxyphysin). Endocrinology 107: 1880–1891, 1980.PubMedCrossRefGoogle Scholar
  17. 17.
    Tasso F, Rua S, Picard D: Cytochemical duality of neurosecretory material in the hypothal- amo-posthypophysial system of the rat as related to hormone content. Cell Tiss Res 180: 11–29, 1977.CrossRefGoogle Scholar
  18. 18.
    Rosenoir JC, North WG, Moore GJ: Putative precursors of vasopressin, oxytocin, and neurophysins in the rat hypothalamus. Endocrinology 109: 1067 - 1072, 1981.CrossRefGoogle Scholar
  19. 19.
    Lauber M, Camier M, Cohen P: Immunological and biochemical characterization of distinct high molecular weight forms of neurophysin and somatostatin in mouse hypothalamic extracts. FEBS Letters 97: 343–347, 1979.PubMedCrossRefGoogle Scholar
  20. 20.
    Nicolas P, Camier M, Lauber M, Masse MJO, Mohring J, Cohen P: Immunological identification of high molecular weight forms common to bovine neurophysin and vasopressin. Proc Natl Acad Sci 77: 2587–2591, 1980.PubMedCrossRefGoogle Scholar
  21. 21.
    Cannata, MA, Morris JF: Changes in the appearance of hypothalamo-neurohypophysial neurosecretory granules associated with their maturation. J Endocr 57: 531–538, 1973.PubMedCrossRefGoogle Scholar
  22. 22.
    Russell JT, Holtz RW: Measurement of pH and membrane potential in isolated neurosecretory vesicles from bovine neurohypophyses. J Biol Chem 256: 5950–5953, 1981.PubMedGoogle Scholar
  23. 23.
    Morris JF: Hormone storage in individual neurosecretory granules of the pituitary gland: a quantitative ultrastructural approach to hormone storage in the neural lobe. J Endocr 68: 209–224, 1976.PubMedCrossRefGoogle Scholar
  24. 24.
    North WG, LaRochelle FJ Jr, Hardy GR: Development of radioimmunoassays to individual rat neurophysins. J Endocrinol (in press), 1982.Google Scholar
  25. 25.
    Dreifuss JJ: A review of neurosecretory granules: their contents and mechanism of release. NY Acad Sci 248: 184–201, 1975.CrossRefGoogle Scholar
  26. 26.
    North WG, Gellai M, Hardy G: Oxytocin and oxytocin-associated neurophysin evaluation by RIA in the Brattleboro rat. Ann NY Acad Sci 394: 167 - 172, 1982.PubMedCrossRefGoogle Scholar
  27. 27.
    Rhodes CH, Morrell JI, Pfaff DW: Immunohistochemical analysis of magnocellular elements in rat hypothalamus: Distribution and number of cells containing neurophysin, oxytocin and vasopressin. J Comp Neurol 198: 45–64, 1981.PubMedCrossRefGoogle Scholar
  28. 28.
    Valtin, H, North WG, LaRochelle FT Jr, Sokol HW, Morris JF: Biochemical and anatomical aspects of ADH production. In: Proc VII Int Cong Nephrol. Bergeron M (ed). Basel: Karger, 1978, pp 313–320.Google Scholar
  29. 29.
    North WG, Valtin H: The purification of rat neurophysins by a method of preparative polyacrylamide gel electrophoresis. Analyt Biochem 78: 436–450, 1976.CrossRefGoogle Scholar
  30. 30.
    North WG, Valtin H, Morris JF, LaRochelle FT Jr: Evidence for metabolic conversions of rat neurophysins within neurosecretory granules of the hypothalamo-neurohypophysial system. Endocrinology 101: 110–118, 1977.PubMedCrossRefGoogle Scholar
  31. 31.
    North WG, Mitchell TI: Evolution of neurophysin proteins: The partial sequence of rat neurophysins. FEBS Letters 126: 41–44, 1981.PubMedCrossRefGoogle Scholar
  32. 32.
    Chauvet M-T, Chauvet J, Acher R: Identification of rat neurophysins: Complete amino acid sequences of MSEL- and VLDV-neurophysins. Biochem Biophys Res Commun 103: 595–603, 1981.PubMedCrossRefGoogle Scholar
  33. 33.
    North WG, Valtin H, Morris JF: Evidence for enzymatic (metabolic) conversion of rat neurophysins. Clin Res 24: 429A, 1976.Google Scholar
  34. 34.
    North WG, Morris JF, LaRochelle FT Jr, Valtin H: Enzymatic interconversions of neurophysins. In: Neurophypophysis. Moses AM, Share L (eds). Basel: Karger, 1977, pp 43–52.Google Scholar
  35. 35.
    Smyth DG, Massey D: A new glycopeptide in pig, ox and sheep pituitary. Biochem Biophys Res Commun 87: 1006–1010, 1979.PubMedCrossRefGoogle Scholar
  36. 36.
    Pickering BR: The molecules of neurosecretion: their formation, transport and release. Prog Horm Res 45: 161–179, 1976.Google Scholar
  37. 37.
    Marks N, Lajtha A: Protein and polypeptide breakdown. In: Handbook of Neurochemistry 5A. Lajtha A (ed). New York: Plenum, 1971, p 49.Google Scholar
  38. 38.
    Steiner DF: Peptide hormone precursors: biosynthesis, processing and significance. In: Peptide Hormones. Parsons JA (ed). London: MacMillan, 1976, pp 49–64.Google Scholar
  39. 39.
    Fletcher DJ, Quigley J, Baver EJ, Noe BD: Characterization of pro-insulin and proglucagon-converting activities in isolated islet secretory granules. J Cell Biol 90: 312–322, 1981.PubMedCrossRefGoogle Scholar
  40. 40.
    Sawyer WH, Knobil E (eds): Handbook of Physiology, volume IV, The Pituitary Gland and its neuroendocrine control, Part I. American Physiological Society, 1974.Google Scholar
  41. 41.
    Moses AM, Miller M (eds): Neurohypophysis. Basel: Karger, 1977.Google Scholar
  42. 42.
    Robertson GL: The regulation of vasopressin function in health and disease. Rec Prog Horm Res 33: 333–385, 1977.Google Scholar
  43. 43.
    Pullan PT, Clappison BH, Johnston CI: Plasma vasopressin and human neurophysins in physiological and pathological states associated with changes in vasopressin secretion. J Clin Endocrinol Metab 49: 580–587, 1979.PubMedCrossRefGoogle Scholar
  44. 44.
    Forsling ML, Iverson LL, Lightman SL: Dopamine and enkephalin directly inhibit vasopressin release from the neurohypophysis. J Physiol 319: 66P, 1981.Google Scholar
  45. 45.
    Robinson AG : Neurophysins and their physiological significance. In: Neuroendocrinology, Krieger DT, Hughes JC (eds)., Sunderland: Sinauer Assoc Inc, 1980, p 149.Google Scholar
  46. 46.
    Yalow RS: Big ACTH and bronchogenic carcinoma. Ann Rev Med 30: 241–248, 1979.PubMedCrossRefGoogle Scholar
  47. 47.
    Wallach SR, Royston T, Taetle R, Wohl H, Deftos LJ: Plasma calcitonin as a marker of disease activity in patients with small cell carcinoma of the lung. J Clin Endocrinol Metab 53: 602–606, 1981.PubMedCrossRefGoogle Scholar
  48. 48.
    Rees LH: The biosynthesis of hormones by non-endocrine tumors — a review. J Endocr 67: 143–174, 1975.PubMedCrossRefGoogle Scholar
  49. 49.
    North WG, Maurer LH, Valtin H, O’Donnell J: Human neurophysins as potential tumor markers for small cell carcinoma of the lung: Application of specific radioimmunoassays for vasopressin-associated and oxytocin-associated neurophysins. J Clin Endocrinol Metab 51: 892–896, 1980.PubMedCrossRefGoogle Scholar
  50. 50.
    Fenestril DD: Hyposmolar syndromes. In: Disturbances in the Body Fluid Osmolality. Andreoli TE, Grantham JJ, Rector FC Jr (eds). Bethesda: American Physiological Society, 1977, p 267.Google Scholar
  51. 51.
    Miller M, Moses AM: Radioimmunoassay of urinary antidiuretic hormone in man: Response to water load and dehydration in normal subjects. J Clin Endocrinol Metab 34: 537–545, 1972.PubMedCrossRefGoogle Scholar
  52. 52.
    Maurer LH, Tulloh M, Weiss RB, Blom J, Leone L, Glidewell O, Pajak TF: A randomized combined modality trial in small cell carcinoma of the lung. Cancer 45: 30–39, 1980.PubMedCrossRefGoogle Scholar
  53. 53.
    Greco FA, Richardson RL, Snell JD, Stroup SL, Oldham RK: Small cell cancer: Complete remission and improved survival. Am J Med 66: 625–630, 1979.PubMedCrossRefGoogle Scholar
  54. 54.
    LaRochelle FT Jr, North WG, Stern P: A new extraction of arginine vasopressin from blood: the use of octadecasilyl-silica. Pflugers Arch Eur J Physiol 387: 79–81, 1980.CrossRefGoogle Scholar
  55. 55.
    North WG, LaRochelle FT Jr, Haldar J, Sawyer WH, Valtin H: Characterization of an antiserum used in a radioimmunoassay for arginine-vasopressin: implications for reference standards. Endocrinology 103: 1976–1984, 1978.PubMedCrossRefGoogle Scholar
  56. 56.
    Yamaji T, Ishibashi M, Katayama S: Nature of the immunoreactive neurophysins in ectopic vasopressin-producing oat-cell carcinomas of the lung. J Clin Invest 68: 388–398, 1981.PubMedCrossRefGoogle Scholar
  57. 57.
    Pettengill OS, Sorenson GD: Tissue culture and in vitro characteristics in small cell carcinoma. In: Small Cell Lung Cancer, Greco FA, Oldham RK, Bunn PA Jr (eds). New York: Grune and Stratton, 1981.Google Scholar
  58. 58.
    George JM, Capen CC, Philips AS: Biosynthesis of vasopressin in vitro and ultrastructure of a bronchogenic carcinoma. Patient with syndrome of inappropriate secretion of antidiuretic hormone. J Clin Invest 51: 141–148, 1972.PubMedCrossRefGoogle Scholar
  59. 59.
    Klein LA, Rabson AS, Worksman J: In vitro synthesis of vasopressin by lung tumor cells. Surg Forum 20: 231–233, 1969.PubMedGoogle Scholar
  60. 60.
    Goldenberg DM, DeLand F, Kim E, Bennett S, Primus FJ, Van Nagell JR, Estes N, DeSimone P, Rayburn P: Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. New Eng J Med 298: 1384–1388, 1978.PubMedCrossRefGoogle Scholar
  61. 61.
    Goldenberg DM, Kim EE, DeLand FH, Bennett S, Primus J: Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen. Cancer Research 40: 2984–2992, 1980.PubMedGoogle Scholar
  62. 62.
    Glennie MJ, Stevenson GT: Univalent antibodies kill tumor cells in vitro and in vivo. Nature 295:712–714, 1982.PubMedCrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers, Boston 1983

Authors and Affiliations

  • William G. North
  • L. Herbert Maurer
  • Joseph F. O’Donnell

There are no affiliations available

Personalised recommendations