Oxytocin and Vasopressin: After the Genes, What Next?

  • Harold Gainer
  • Miriam Altstein
  • Yoshinobu Hara


It is now almost sixty years since Ernst Scharrer, in a paper emanating from his doctoral dissertation studies at the University of Munich (Scharrer, 1928), first described the gland-like secretory characteristics of the magnocellular neurons in the preoptic nucleus of the minnow, Phloxinus laevis. This discovery and its bold interpretation, i.e., the theory of neurosecretion, although initally received sceptically by the scientific community, was to become, largely through the subsequent heroic efforts of Ernst and Berta Scharrer, and their close colleague W. Bargmann (Bargmann and Scharrer, 1951; Sano, 1985), one of the most heuristic concepts in modern neurobiology. Not only did this concept usher in the present highly active era of neuroendocrinology, but also the even more explosive field of neuropeptide research in general (Scharrer, 1987).


Magnocellular Neuron Hybridization Histochemistry Vasopressin Gene Vasopressin mRNA Hypothalamic mRNA 
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  1. Bargmann, W., and Scharrer, E., 1951, The origin of the posterior pituitary hormones, Am. Scientist, 39: 255.Google Scholar
  2. Brownstein, M.J., and Gainer, H., 1977, Neurophysin biosynthesis in normal rats and in rats with hereditary diabetes insipidus, Proc. Natl. Acad. Sci. USA., 269: 259.Google Scholar
  3. Burbach, J.P.H., De Hoop, M.J., Schmale, H., Richter, D., De Kloet, E.R., Ten Haaf, J.A., and De Wied, D., 1984, Differential responses to osmotic stress of vasopressinneurophysin mrna in hypothalamic nuclei, Neuroendocrinologv, 39: 582.CrossRefGoogle Scholar
  4. Burbach, J.P.H., Van Tol, H.H.M., Bakkus, M.H.C., Schmale, H. and Ivell, R., 1986, Quantitation of vasopressin mRNA and oxytocin mRNA in hypothalamic nuclei by solution hybridization assays, J. Neurochem., 47: 1814.CrossRefGoogle Scholar
  5. Castel, M., Dellmann, H.-D., and Gainer, H., 1984, Neuronal secretory systems, Int. Rev. Cvtol., 88: 303.CrossRefGoogle Scholar
  6. Davis, L.G., Arentzen, R., Reid, J.M., Manning, R.W., Wolfson, B., Lawrence, K.L., and Baldino, F., Jr., 1986, Glucocorticoid sensitivity of vasopressin mRNA levels in the paraventricular nucleus of the rat Proc. Natl. Acad. Sci. USA, 83: 1145.CrossRefGoogle Scholar
  7. Douglass, J., Civelli, O., and Herbert, E., 1984, Polyprotein gene expression: generation of diversity of neuroendocrine peptides. Ann. Rev. Biochem., 53: 665.CrossRefGoogle Scholar
  8. Einspanier, R., Pitzel, L., Wuttke, W., Hagendorff, G., Richter, K.D., Kardalinou, E. and Scheit, K.H., 1986, Demonstration of mRNAs for oxytocin and prolactin in porcine granulosa and luteal cells, FEBS Lett., 204: 37.CrossRefGoogle Scholar
  9. Fuller, P.J., Clements, J.A., and Funder, J.W., 1985a, Localization of arginine-vasopressinneurophysin II messenger ribonucleic acid in the hypothalamus of control and Brattleboro rats by hybridization histochemistry with a synthetic pentadecamer oligonucleotide probe, Endocrinology, 116: 2366.CrossRefGoogle Scholar
  10. Fuller, P.J., Clements, J.A., Lolait, S.J., and Funder, J.W., 1984, Expression of the gene for arginine vasopressin in Brattleboro rats, J. Hypertension, 2: 305.Google Scholar
  11. Fuller, P.J., Clements, J.A., Tregear, G.W., Nicolaides, I., Whitfeld, P.L., and Funder, J.W., 1985b, Vasopressin-neurophysin II gene expression in the ovary: studies in Sprague-Dawley, Long-Evans, and Brattleboro rats, J. Endocrinology, 105: 317.CrossRefGoogle Scholar
  12. Gainer, H., 1983, Precursors of vasopressin and oxytocin, Prog in Brain Res., 60: 205.CrossRefGoogle Scholar
  13. Gainer, H., Russell, J.T., and Loh, Y.P., 1985, The enzymology and intracellular organization of peptide precursor processing: the secretory vesicle hypothesis, Neuroendocrinologv, 40: 171.CrossRefGoogle Scholar
  14. Geenen, V., Legros, J.J., Franchimont, P., Baudrihaye, M., Defresne, M.P., and Boniver, J., 1986, The neuroendocrine thymus: coexistence of oxytocin and neurophysin in the human thymus, Science, 232: 508.CrossRefGoogle Scholar
  15. Geenen, V., Legros, J.J., Franchimont, P., Defresne, M.P., Boniver, J., Ivell, R., and Richter, D., 1987, The thymus as a neuroendocrine organ: synthesis of vasopressin and oxytocin in human thymic epithelium, Ann. N.Y. Acad. Sci., 496: 56.CrossRefGoogle Scholar
  16. Hanley, M.R., Benton, H.P., Lightman, S.L., Todd, K., Bone, E.A., Fretten, P., Palmer, S., Kirk, C.J., and Michell, R.H., 1984, A vasopressin-like peptide in the sympathetic nervous system, Nature, 309: 258.CrossRefGoogle Scholar
  17. Ive11, R., and Richter, D., 1984a, Structure and comparison of the oxytocin and vasopressin genes from rat, Proc. Natl, Acad. Sci. USA, 81: 2006.CrossRefGoogle Scholar
  18. Ivell, R., and Richter, D., 1984b, The gene for the hypothalamic peptide hormone oxytocin is highly expressed in the bovine corpus luteum: biosynthesis, structure, and sequence analysis, EMBO J., 3: 2351.Google Scholar
  19. Ivell, R., Brackett, K.H., Fields, M.H., and Richter, D., 1985, Ovulation triggers oxytocin gene expression in the bovine ovary, FEBS Lett., 190: 263.CrossRefGoogle Scholar
  20. Ive11, R., Schmale, H., Krisch, B., Nahke, P. and Richter, D., 1986, Expression of a mutant vasopressin gene: differential polyadenylation and read-through of the mRNA 3’end in a frame shift mutant, EMBO J., 5: 971.Google Scholar
  21. Loh, Y.P., Brownstein, M.J., and Gainer, H., 1984, Proteolysis in neuropeptide processing and other neural functions, Ann. Rev. Neurosci., 7: 189.CrossRefGoogle Scholar
  22. Majzoub, J.A., Pappey, A., Burg, R., and Habener, J.J., 1984, Vasopressin gene is expressed at low levels in the hypothalamus of the Brattleboro rat, Proc. Natl. Acad. Sci. USA, 81: 5296.CrossRefGoogle Scholar
  23. McCabe, J.T., Morrell, J.I., and Pfaff, D.W., 1986a, Measurement of expression of the vasopressin and oxytocin genes in single neurons by in situ hybridization, in: Fink, G., Harmar, A.J., and McKerns, K.W. (eds.), Neuroendocrine Molecular Biology, Plenum Press, New York, pp. 219–229.Google Scholar
  24. McCabe, J.T., Morrell, J.I., Ive11, R., Schmale, H., Richter, D., and Pfaff, D.W., 1986b, Brattleboro rat hypothalamic neurons transcribe vasopressin gene: evidence from in situ hybridization, Neuroendocrinologv, 44: 361.CrossRefGoogle Scholar
  25. Nojiri, H., Ishida, I., Miyashita, E., Sato, M., Urano, A. and Deguchi, T., 1987, Cloning and sequence analysis of cDNAs for neurohypophysial hormones vasotocin and mesotocin for the hypothalamus of toad, Bufo japonicus, Proc. Natl. Acad. Sci USA, 84: 3043.CrossRefGoogle Scholar
  26. Nojiri, H., Sato, M., and Urano, A., 1985, In situ hybridization of the vasopressin in mRNA in the rat hypothalamus by use of a synthetic oligonucleotide probe, Neurosci. Lett., 58: 101.CrossRefGoogle Scholar
  27. Nussey, S.S., Ang, V.T.Y., Jenkins, J.S., Chowdry, H.S., and Bissett, G.W., 1984, Brattleboro rat adrenal contains vasopressin, Nature, 310: 64.CrossRefGoogle Scholar
  28. Orci, L., Ravazzola, A.M., Amersherdt, M., Madsen, O., Vassali, J.D. and Perelet, A., 1985, Direct identification of prohormone conversion site in insulin-secreting cells, Cell. 42: 671.CrossRefGoogle Scholar
  29. Rebhein, M., Hillers, M., Mohr, E., Ivell, R., Morley, S., Schmale, H. and Richter D., 1986, The neurohypophysial hormones vasopressin and oxytocin, Biol. Chem. Home-Sevier, 367: 695.Google Scholar
  30. Reppert, S.M. and Uhl, G.R., 1987, Vasopressin messenger ribonucleic acid in supraoptic and suprachiasmatic nuclei: appearance and circadian regulation during development, Endocrinology, 120: 2483.CrossRefGoogle Scholar
  31. Ruppert, S.D., Scherer, G., and Schutz, G., 1984, Recent gene conversion involving bovine vasopressin and oxytocin precursor genes suggested by nucleotide sequence, Nature, 308: 554.CrossRefGoogle Scholar
  32. Sano, Y., 1985, History of Neurosecretion, in: Neurosecretion and the Biology of Neuropeptides ( Kobayashi, H., Bern, H.A., and Urano, A., Eds.) pp 1–7, Japan Sci. Soc. Press, Tokyo/Springer-Verlag, Berlin.Google Scholar
  33. Sausville, E., Carney, D., and Battey, J., 1985, The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line, J. Biol. Chem., 260: 10236.Google Scholar
  34. Scharrer, B., 1987, Neurosecretion: Beginnings and new directions in neuropeptide research, Ann. Rev. Neurosci., 10: 1.CrossRefGoogle Scholar
  35. Scharrer, E., 1928, Die lichtempfindlichkeit blinder elritzen (Untersuchungen uber das zwischenhirn der fische), Z. Veral. Phvsiol., 7: 1.CrossRefGoogle Scholar
  36. Schmale, H., and Richter, D., 1984, Single base deletion in the vasopressin gene is the cause of diabetes insipidus in Brattleboro rats, Nature, 308: 705CrossRefGoogle Scholar
  37. Schmale, H., Heinsohn, S., and Richter, D., 1983, Structural organization of the rat gene for the arginine-vasopressin-neurophysin precursor, EMBO J., 2: 763.Google Scholar
  38. Schmale, H., Ivell, R., Breindel, M., Darmer, D., and Richter, D., 1984, The mutant vasopressin gene from diabetes insipidus ( Brattleboro) rats is transcribed but the message is not efficiently translated, EMBO J., 3: 3289.Google Scholar
  39. Sherman, T.G., Civelli, O., Douglass, J., Herbert, E., Burke, S., and Watson, S.J., 1986b, Hypothalamic dynorphin and vasopressin mRNA expression in normal and Brattleboro rats, Federation Proc., 45: 2323.Google Scholar
  40. Sherman, T.G., Civelli, O., Douglass, J., Herbert, E., and Watson, S.J., 1986c, Coordinate expression of hypothalamic pro-dynorphin and pro-vasopressin mRNAs with osmotic stimulation, Neuroendocrinologv, 44: 222.CrossRefGoogle Scholar
  41. Sherman, T.G., McKelvy, J., and Watson, S.J., 1986a, Vasopressin mRNA regulation in individual hypothalamic nuclei: a northern and in situ hybridization analysis, L Neurosci., 6: 1685.Google Scholar
  42. Silverman, A., and Zimmerman, E.A., 1983, Magnocellular neurosecretory system, Ann. Rev. Neurosci., 6: 357.CrossRefGoogle Scholar
  43. Sofroniew, M.V., 1985, Vasopressin, oxytocin and their related neurophysins, in: Handbook of Chemical Neuroanatomy, vol. 4, Part I, edited by A. Bjorklund, and T. Hokfelt. pp. 93–165. Elsevier Science Publishers, Amsterdam.Google Scholar
  44. Swanson, L.W., and Sawchenko, P.E., 1983, Hypothalamic integration: organization of the paraventricular and supraoptic nuclei, Ann. Rev. Neurosci., 6: 269.CrossRefGoogle Scholar
  45. Tooze, J., Hollinshead, M., Frank, R., and Burke, B., 1987, An antibody specific for an endoproteolytic cleavage site provides evidence that pro-opiomelanocortin is packaged into secretory granules in AtT20 cells before its cleavage, J. Cell Biol., 105: 155.CrossRefGoogle Scholar
  46. Uhl, G.R., and Reppert, S.M., 1986, Suprachiasmatic nucleus vasopressin messenger RNA: Circadian variation in normal and Brattleboro rats, Science, 232: 390.CrossRefGoogle Scholar
  47. Uhl, G.R., Zingg, H.H., and Habener, J.F., 1985, Vasopressin mRNA in situ hybridization: Localization and regulation studied with oligonucleotide cDNA probes in normal and Brattleboro rat hypothalamus, Proc. Natl. Acad. Sci. USA, 82: 5555.CrossRefGoogle Scholar
  48. Valtin, H., Stewart, J., and Sokol, H.W., 1974, Genetic control of the production of posterior pituitary principles. in: Handbook of Physiology, Section 7, Endocrinology, Vol. IV, Part I, edited by R.O. Greep, and E.B. Astwood, pp. 131–171. Amer. Soc. Physiol., Wash., D.C.Google Scholar
  49. Van Tol, H.H.M., 1987, Regulation of vasopressin and oxytocin gene expression in the hypothalamo-neurohypophyseal system of the rat, Ph.D. thesis, University of Utrecht, The Netherlands, 177 pp.Google Scholar
  50. Van Tol, H.H.M., Voorhuis, D.T.A.M., and Burbach, J.P.H., 1987, Oxytocin gene expression in discrete hypothalamic magnocellular cell groups is stimulated by prolonged salt loading, Endocrinology, 120: 71.CrossRefGoogle Scholar
  51. Van Tol, H.H.M., Voorhuis, T.A.M., Snijdewint, F.G.M., Boer, G.J., and Burbach, J.P.H., 1986, Vasopressin gene expression is attenuated in the fetal Brattleboro rat, FEES Lett., 204: 101.CrossRefGoogle Scholar
  52. Wathes, D.C., 1984, Possible actions of gonadal oxytocin and vasopressin, J. Reorod. Fertil., 71: 315.CrossRefGoogle Scholar
  53. Whitnall, M.H., Key, S., Ben-Barak, Y., Ozato, K., and Gainer, H., 1985, Neurophysin in the hypothalamo-neurohypophysial system. II. Immunocytochemical studies of the ontogeny of oxytocinergic and vasopressinergic neurons, J. Neurosci., 5: 98.Google Scholar
  54. Wolfson, B., Manning, R.W., Davis, L.G., Arentzen, R., and Baldino, F. Jr., 1985, Co-localization of corticotropin releasing factor and vasopressin mRNA in neurons after adrenalectomy, Nature, 315: 59.CrossRefGoogle Scholar
  55. Young, W.S. III, 1986, Corticotropin-releasing factor mRNA in the hypothalmus is affected differently by drinking saline and by dehydration, FEBS Lett., 208: 158.CrossRefGoogle Scholar
  56. Young, W.S., III, Mezey, E., and Siegel, R.E., 1986a, Quantitative in situ hybridization histochemistry reveals increased levels of corticotropin-releasing factor mRNA after adrenalectomy in rats, Neurosci. Lett., 20: 198.CrossRefGoogle Scholar
  57. Young, W.S., III, Mezey, E., and Siegel, R.E., 1986b, Vasopressin and oxytocin mRNAs in adrenalectomized and Brattleboro rats: analysis by quantitative in situ hybridization histochemistry, Mol. Brain Res., 1: 231.CrossRefGoogle Scholar
  58. Zingg, H.H., Almazan, G., and Lefebvre, D.L., 1987, Osmotic stress induces an important increase in vasopressin mRNA poly (A) tail length: A novel mechanism of vasopressin gene control? 69th Ann. Meet. Endocrine Society, pp. 135 (Abstract 456).Google Scholar
  59. Zingg, H.H., Lefebvre, D., and Almazan, G., 1986, Regulation of vasopressin gene expression in rat hypothalamic neurons. Response to osmotic stimulation. J. Biol. Chem. 261: 12956.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Harold Gainer
    • 1
  • Miriam Altstein
    • 1
  • Yoshinobu Hara
    • 1
  1. 1.Laboratory of Neurochemistry National Institutes of HealthNINCDSBethesdaUSA

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