Skip to main content
SpringerLink
Log in

Transgenic Models for Oxytocin and Vasopressin

  • Chapter
Transgenics in Endocrinology

Part of the book series: Contemporary Endocrinology ((COE))

  • 107 Accesses

Abstract

Oxytocin (OT) and arginine vasopressin (AVP) were among the first peptide hormones to be isolated and sequenced (1). Both OT and AVP consist of nine amino acids that form a ring structure from disulfide bonds, bridging two cysteine residues. Although the two hormones are similar in structure, differing at only two positions, their functions appear to be quite distinct. Oxytocin has been implicated in the induction of labor during parturition, milk ejection during lactation (2), and the control of reproductive and maternal behaviors (3). Arginine vasopressin, also known as antidiuretic hormone, plays a crucial role in maintaining osmotic homeostasis and vascular tone, and has more recently been implicated in cognition and social behaviors (4–6).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. du Vingeaud V, Ressler C, Trippett S. The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. J Biol Chem 1953; 205: 949–957.

    Google Scholar 

  2. Gainer H, Wray W. Cellular and molecular biology of oxytocin and vasopressin. In: Knobil E, Neill JD, eds. The Physiology of Reproduction. Raven Press, New York, NY, 1994, pp. 1099–1129.

    Google Scholar 

  3. Insel TR, Young L, Wang Z. Central oxytocin and reproductive behaviours. Rev Reprod 1997; 2: 28–37.

    Article  PubMed  CAS  Google Scholar 

  4. de Wied D. Neuropeptides in learning and memory. Behav Brain Res 1997; 83: 83–90.

    Article  PubMed  Google Scholar 

  5. Engelmann M, Wotjak CT, Neumann I, Ludwig M, Landgraf R. Behavioral consequences of intracerebral vasopressin and oxytocin: focus on learning and memory. Neurosci Biobehav Rev 1996; 20: 341–358.

    Article  PubMed  CAS  Google Scholar 

  6. Young LJ, Wang Z, Insel TR. Neuroendocrine bases of monogamy. TINS 1998; 21: 71–75.

    PubMed  CAS  Google Scholar 

  7. Swanson LW, Sawchenko PE. Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annu Rev Neurosci 1983; 6: 269–324.

    Article  PubMed  CAS  Google Scholar 

  8. Mohr E, Bahnsen U, Kiessling C, Richter D. Expression of the vasopressin and oxytocin genes in rats occurs in mutually exclusive sets of hypothalamic neurons. FEBS Lett 1988; 242: 144–148.

    Article  PubMed  CAS  Google Scholar 

  9. Brownstein M, Russell J, Gainer H. Synthesis, transport and release of posterior pituitary hormones. Science 1980; 207: 373–387.

    Article  PubMed  CAS  Google Scholar 

  10. Lefebvre DL, Giad A, Bennet H, Lariviere R, Zingg HH. Oxytocin gene expression in the uterus. Science 1992; 1553–1555.

    Google Scholar 

  11. lvell R, Brackett KH, Fields MJ, Richter D. Ovulation triggers oxytocin gene expression in the bovine ovary. FEBS Lett 1985; 190: 263–267.

    Article  Google Scholar 

  12. Jankowski M, Hajjar F, Kawas SA, Mukaddam-Daher S, Hoffman G, McCann SM, et al. Rat heart: a site of oxytocin production and action. Proc Natl Acad Sci USA 1998;95:14, 558–14, 563.

    Google Scholar 

  13. Ang HL, Ungefroren H, de Bree F, Foo NC, Carter D, Burbach JP, et al. Testicular oxytocin gene expression in seminiferous tubules of cattle and transgenic mice. Endocrinology 1991; 128: 21 10–2117.

    Google Scholar 

  14. Schmale H, Heinsohn S, Richter D. Structural organization of the rat gene for the arginine vasopressinneurophysin precursor. EMBO J 1983; 2: 763–767.

    PubMed  CAS  Google Scholar 

  15. Ivell R, Richter D. Structure and comparison of the oxytocin and vasopressin genes from rat. Proc Natl Acad Sci USA 1984; 81: 2006–2010.

    Article  PubMed  CAS  Google Scholar 

  16. Hara Y, Battey J, Gainer H. Structure of mouse vasopressin and oxytocin receptor genes. Mol Brain Res 1990; 8: 319–324.

    Article  PubMed  CAS  Google Scholar 

  17. Schmitz E, Mohr E, Richter D. Rat vasopressin and oxytocin genes are linked by a long interspersed repeated DNA element (LINE): sequence and transcriptional analysis of LINE. DNA Cell Biol 1991; 10: 81–91.

    Article  PubMed  CAS  Google Scholar 

  18. Sausville E, Carney D, Battey J. The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer line. J Biol Chem 1985;260:10, 236–10, 241.

    Google Scholar 

  19. Gautvik KM, de Leeca L, Gautvik VT, Danielson PE, Tranque P, Dopazo A, et al. Overview of the most prevalent hypothalamus-specific mRNA’s as identified by directional tag PCR subtraction. Proc Natl Acad Sci USA 1996; 93: 8733–8738.

    Article  PubMed  CAS  Google Scholar 

  20. Lightman SL, Young III WS. Vasopressin, oxytocin, dynorphin, enkephalin, and corticotrophin releasing factor mRNA stimulation in the rat. J Physiol 1987; 394: 23–39.

    PubMed  CAS  Google Scholar 

  21. Van Tol HHM, Bolwerk ELM, Liu B, Burbach JPH. Oxytocin and vasopressin gene expression in hypothalamo-neurohypophyseal system of the rat during the estrous cycle, pregnancy, and lactation. Endocrinology 1988; 122: 945–951.

    Article  PubMed  Google Scholar 

  22. Zingg HH, Rozen F, Chu K, Larcher A, Arslan A, Richard S, et al. Oxytocin and oxytocin receptor gene expression in the uterus. Rec Prog Horm Res 1995; 50: 255–273.

    PubMed  CAS  Google Scholar 

  23. Barberis C, Tribollet E. Vasopressin and oxytocin receptors in the central nervous system. Crit Rev Neurobiol 1996; 10: 119–154.

    Article  PubMed  CAS  Google Scholar 

  24. Larcher A, Neculcia J, Breton C, Arslan A, Rozen F, Russo C, et al. Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment. Endocrinology 1995; 136: 5350–5356.

    Article  PubMed  CAS  Google Scholar 

  25. Quinones-Jenab V, Jenab S, Ogawa S, Adan RAM, Burbach JP, Pfaff DW. Effects of estrogen on oxytocin receptor messenger ribonucleic acid expression in the uterus, pituitary, and forebrain of the female rat. Neuroendocrinology 1997; 65: 9–17.

    Article  PubMed  CAS  Google Scholar 

  26. Young III WS, Reynolds K, Shepard EA, Gainer H, Castel M. Cell-specific expression of the rat oxytocin gene in transgenic mice. J Neuroendocrinol 1990; 2: 917–925.

    Article  PubMed  CAS  Google Scholar 

  27. Belenky M, Castel M, Young III WS, Gainer H, Cohen S. Ultrastructural immunolocalization of rat oxytocin-neurophysin in transgenic mice expressing the rat oxytocin gene. Brain Res 1992; 583: 279–286.

    Article  PubMed  CAS  Google Scholar 

  28. Ho MY, Carter DA, Ang HL, Murphy D. Bovine oxytocin transgenes in mice. J Biol Chem 1995;270:27, 199–27, 205.

    Google Scholar 

  29. Ho MY, Murphy D. A bovine oxytocin transgene in mice: expression in the female reproductive organs and regulation during pregnancy, parturition and lactation. Mol Cell Endocrinol 1997; 136: 15–21.

    Article  PubMed  CAS  Google Scholar 

  30. Ivell R, Rust W, Einsanier A, Hartung S, Fields M, Fuchs AR. Oxytocin and oxytocin receptor gene expression in the reproductive tract of the pregnant cow: rescue of luteal oxytocin production at term. Biol Reprod 1995; 53: 553–560.

    Article  PubMed  CAS  Google Scholar 

  31. Grant FD, Reventos J, Gordon JW, Kawabata S, Miller M, Majzoub JA. Expression of the rat arginine vasopressin gene in transgenic mice. Mol Endocrinol 1993; 7: 659–667.

    Article  PubMed  CAS  Google Scholar 

  32. Zingg HH, Lefebvre DL, Almazan G. Regulation of poly(A) tail size of vasopressin mRNA. J Biol Chem 1988;263:11, 041–11, 043.

    Google Scholar 

  33. Miller M, Kawabata S, Wiltshire-Clement M, Reventos J, Gordon JW. Increased vasopressin secretion and release in mice transgenic for the rat arginine vasopressin gene. Neuroendocrinology 1993; 57: 621–625.

    Article  PubMed  CAS  Google Scholar 

  34. Miller M, Haroutunian V, Wiltshire-Clement M. Altered alertness of vasopressin-secreting transgenic mice. Peptides l995; 16: 1329–1333.

    Google Scholar 

  35. Ang HL, Carter DA, Murphy D. Neuron-specific expression and physiological regulation of bovine vasopressin transgenes in mice. EMBO J 1993; 12: 2397–2409.

    PubMed  CAS  Google Scholar 

  36. Zeng Q, Carter DA, Murphy D. Cell specific expression of a vasopressin transgene in rats. J Neuroendocrinol 1994; 6: 469–477.

    Article  PubMed  CAS  Google Scholar 

  37. Waller S, Fairhall KM, Iain JX, Robinson CAF, Murphy D. Neurohypophyseal and fluid homeostasis in transgenic rats expressing a tagged rat vasopressin prepropeptide in hypothalamic neurons. Endocrinology 1996; 137: 5068–5077.

    Article  PubMed  CAS  Google Scholar 

  38. Venkatesh B, Si-Hoe SL, Murphy D, Brenner S. Transgenic rats reveal functional conservation of regulatory controls between Fugu isotocin and rat oxytocin genes. Proc Natl Acad Sci USA 1997;94:12, 462–12, 466.

    Google Scholar 

  39. Brenner S, Elgar G, Sandford R, Macrae A, Venkatesh B, Aparicio S. Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome. Nature 1993; 366: 265–268.

    Article  PubMed  CAS  Google Scholar 

  40. Goossens N, Diericks K, Vandesande F. Immunocytochemical localization of vasotocin and isotocin in the preopticohypophysial neurosecretory system of teleosts. Gen Comp Endocrinol 1977; 32: 371–375.

    Article  PubMed  CAS  Google Scholar 

  41. Hyodo S, Urano A. Changes in expression of provasotocin and proisotocin genes during adaptation to hyper-and hypo-osmotic environments in rainbow trout. J Comp Physiol B 1991; 161: 549–556.

    Article  PubMed  CAS  Google Scholar 

  42. Verma IM, Somia N. Gene therapy-promises, problems and prospects. Nature 1997; 389: 239–242.

    Article  PubMed  CAS  Google Scholar 

  43. Geddes BJ, Harding TC, Lightman SL, Uney JB. Long-term gene therapy in the CNS: reversal of hypthalamic diabetes insipidus in the Brattleboro rat by using an adenovirus expressing arginine vasopressin. Nat Med 1997; 3: 1402–1404.

    Article  PubMed  CAS  Google Scholar 

  44. Schmale H, Richter D. Single base deletion in the vaspressin gene is the cause of diabetes insipidus in Brattleboro rats. Nature 1984; 308: 705–709.

    Article  PubMed  CAS  Google Scholar 

  45. Nishimori K, Young LJ, Guo Q, Wang Z, Insel TR, Matzuk MM. Oxytocin is required for nursing but is not essential for parturition or reproductive behavior. Proc Natl Acad Sci USA 1996;93: 11, 699–11, 704.

    Google Scholar 

  46. Young LJ, Winslow JT, Wang Z, Gingrich B, Guo Q, Matzuk MM, et al. Gene targeting approaches to neuroendocrinology: oxytocin, maternal behavior, and affiliation. Horm Behav 1997; 31: 221–231.

    Article  PubMed  CAS  Google Scholar 

  47. Young III WS, Shepard E, Amico J, Hennighausen L, Wagner KU, LaMarca ME, et al. Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition. J Neuorendocrinol 1996; 8: 847–853.

    Article  CAS  Google Scholar 

  48. Gross GA, Imamura T, Luedke C, Vogt SK, Olson LM, Nelson DM, et al. Opposing actions of prostoglandins and oxytocin determine the onset of murine labor. Proc Natl Acad Sci USA 1998;95:11, 875–11, 879.

    Google Scholar 

  49. DeVries AC, Young III WS, Nelson RJ. Reduced aggressive behavior in mice with targeted disruption of the oxytocin gene. J Neuroendocrinol 1997; 9: 363–368.

    Article  PubMed  CAS  Google Scholar 

  50. Li M, Liu X, Robinson G, Bar-Peled U, Wagner KU, Young WS, et al. Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc Natl Acad Sci USA 1997; 94: 3425–3430.

    Article  PubMed  CAS  Google Scholar 

  51. Bale TL, Dorsa DM, Johnston CA. Oxytocin receptor mRNA expression in the ventromedial hypothalamus during the estrous cycle. J Neurosci 1995; 15: 5058–5064.

    PubMed  CAS  Google Scholar 

  52. Bale TL, Dorsa DM. Sex differences in and effects of estrogen on oxytocin receptor messenger ribonucleic acid expression in the ventromedial hypothalamus. Endocrinology 1995; 136: 27–32.

    Article  PubMed  CAS  Google Scholar 

  53. Pfaff DW, Schwartz-Giblin S. Cellular and molecular mechanisms of female reproductive behaviors. In: Knobil E, Neill JD, eds. The Physiology of Reproduction. Volume 2. Second Edition., Raven Press, New York, NY, 1994, pp. 107–220.

    Google Scholar 

  54. Schumacher M, Coirini H, Pfaff DW, McEwen BS. Behavioral effects of progesterone associated with rapid modulation of oxytocin receptors. Science 1990; 250: 691–694.

    Article  PubMed  CAS  Google Scholar 

  55. Witt DM, Insel TR. A selective oxytocin antagonist attenuates progesterone facilitation of female sexual behavior. Endocrinology 1991; 128: 3269–3276.

    Article  PubMed  CAS  Google Scholar 

  56. Pedersen CA, Prange Ai. Induction of maternal behavior in virgin rats after intracerebroventricular administration of oxytocin. Proc Natl Acad Sci USA 1979; 76: 6661–6665.

    Article  PubMed  CAS  Google Scholar 

  57. van Leengoed E, Kerker E, Swanson HH. Inhibition of postpartum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles. J Endocrinol 1987; 112: 275–282.

    Article  PubMed  Google Scholar 

  58. Insel TR, Young L, Witt DM, Crews D. Gonadal steroids have paradoxical effects on brain oxytocin receptor. J Neuroendocrinol 1993; 5: 619–628.

    Article  PubMed  CAS  Google Scholar 

  59. Winslow JT, Young LJ, Hearn E, Gingrich B, Wang Z, Guo Q, et al. Phenotypic expression of an oxytocin peptide null mutation in mice. Adv Exp Med Biol 1998; 449: 241–243.

    Article  PubMed  CAS  Google Scholar 

  60. Popik P, Vetulani J, van Ree JM. Social memory and neurohypophyseal hormones. Eur Neuropsychopharmaco11993;3: 200, 201.

    Google Scholar 

  61. Dantzer R, Bluthe RM, Koob GF, Le Moal M. Modulation of social memory in male rats by neurohypophyseal peptides. Psychopharmacol 1987; 91: 363–368.

    Article  CAS  Google Scholar 

  62. Winslow J, Hastings N, Carter CS, Harbaugh C, Insel. TR. A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 1993; 365: 545–548.

    Article  PubMed  CAS  Google Scholar 

  63. Wang Z, Ferris CF, De Vries GJ. Role of septal vasopressin innervation in paternal behavior in prairie voles (Microtus ochrogaster). Proc Natl Acad Sci USA 1994; 91: 400–404.

    Article  PubMed  CAS  Google Scholar 

  64. Young LJ, Winslow JT, Nilsen R, Insel TR. Species differences in Vla receptor gene expression in monogamous and non-monogamous voles: behavioral consequences. Behav Neurosci 1997; 111: 599–605.

    Article  PubMed  CAS  Google Scholar 

  65. Young LJ, Huot B, Nilsen R, Wang Z, Insel TR. Species differences in central oxytocin receptor gene expression: comparative analysis of promoter sequences. J Neuroendocrinol 1996; 8: 777–783.

    Article  PubMed  CAS  Google Scholar 

  66. Insel TR, Shapiro LE. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc Natl Acad Sci USA 1992; 89: 5981–5985.

    Article  PubMed  CAS  Google Scholar 

  67. Insel TR, Wang Z, Ferris CF. Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J Neurosci 1994; 14: 5381–5392.

    PubMed  CAS  Google Scholar 

  68. Young LJ, Waymire KG, Nilsen R, Macgregor GR, Wang Z, Insel TR. The 5’ flanking region of the monogamous prairie vole oxytocin receptor gene directs tissue specific expression in mice. Annu NY Acad Sci 1996; 807: 514–517.

    Article  Google Scholar 

  69. Young LJ, Nilsen R, Waymire KG, MacGregor GR, Insel TR. Increased affiliative response to vasopressin in mice expressing the V l a receptor from a monogamous vole. Nature 1999; 400: 766–768.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Larry J. Young PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas R. Insel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Martin M. Matzuk MD, PhD

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Chester W. Brown MD, PhD

  3. Departments of Pathology, and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    T. Rajendra Kumar PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Young, L.J., Insel, T.R. (2001). Transgenic Models for Oxytocin and Vasopressin. In: Matzuk, M.M., Brown, C.W., Kumar, T.R. (eds) Transgenics in Endocrinology. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-102-2_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-102-2_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9640-6

  • Online ISBN: 978-1-59259-102-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation