Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Characterization of cDNA for precursor of human luteinizing hormone releasing hormone

Abstract

Human reproduction is controlled by the hypothalamic–pituitary–gonadal axis laid down early in fetal development. Luteinizing hormone releasing hormone (LHRH), also termed gonadotropin releasing hormone (GnRH), is a decapeptide1,2 and is a key molecule in this control circuit. It is produced by hypothalamic neurones, secreted in a pulsatile manner into the capillary plexus of the median eminence and effects the release of luteinizing hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary3. The peptide may have further functions, including behavioural ones4, as LHRH or LHRH-like immunoreactivity has been found in gonadal tissue5,6, placenta7,8 and the central nervous system9,10, and exogenously administered LHRH is shown to affect behaviour11,12. To investigate the biosynthesis of LHRH, we have now isolated cloned genomic and cDNA sequences encoding the precursor form of LHRH, the existence of which had been suggested from Chromatographic studies of hypothalamic8,13 and placental8 extracts. These DNA sequences code for a protein of 92 amino acids in which the LHRH decapeptide is preceded by a signal peptide of 23 amino acids and followed by a Gly-Lys-Arg sequence, as expected for enzymatic cleavage of the decapeptide from its precursor14–16 and amidation17 of the carboxy-terminal of LHRH.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Matsuo, H. et al. Biochem. biophys. Res. Commun. 43, 1334–1339 (1971).

    Article  CAS  Google Scholar 

  2. Burgus, R. et al. Proc. natn. Acad. Sci. U.S.A. 69, 278–282 (1972).

    Article  ADS  CAS  Google Scholar 

  3. Schally, A. V. et al. Biochem. biophys. Res. Commun. 43, 393–401 (1971).

    Article  CAS  Google Scholar 

  4. Moss, R. L. Fedn Proc. 36, 1978–1983 (1977).

    CAS  Google Scholar 

  5. Ying, S. Y., Ling, N., Bohlen, P. & Guillemin, R. Endocrinology 108, 1206 (1982).

    Article  Google Scholar 

  6. Bhasin, S., Heber, D., Peterson, M. & Swerdloff, R. Endocrinology 112, 1144–1145 (1983).

    Article  CAS  Google Scholar 

  7. Khodr, G. S. & Siler-Khodr, T. M. Science 207, 315–317 (1980).

    Article  ADS  CAS  Google Scholar 

  8. Gautron, J. P., Pattou, E. & Kordon, C. Molec. cell. Endocr. 24, 1–16 (1981).

    Article  CAS  Google Scholar 

  9. Silverman, A. J. & Krey, L. C. Brain Res. 157, 233–246 (1976).

    Article  Google Scholar 

  10. Samson, W. K. et al. Neuroendocrinology 31, 66–72 (1980).

    Article  CAS  Google Scholar 

  11. Moss, R. L. & McCann, S. M. Science 181, 177–179 (1973).

    Article  ADS  CAS  Google Scholar 

  12. Pfaff, D. W. Science 182, 1148–1150 (1973).

    Article  ADS  CAS  Google Scholar 

  13. Millar, R. P., Ashnelt, C. & Rossier, G. Biochem. biophys. Res. Commun. 74, 720–726 (1977).

    Article  CAS  Google Scholar 

  14. Steiner, D. F. et al. Ann. N. Y. Acad. Sci. 343, 1–16 (1980).

    Article  ADS  CAS  Google Scholar 

  15. Nakanishi, S. et al. Nature 278, 423–427 (1979).

    Article  ADS  CAS  Google Scholar 

  16. Gubler, U. et al. Nature 295, 206–208 (1982).

    Article  ADS  CAS  Google Scholar 

  17. Bradbury, A. F., Finnie, M. D. A. & Smyth, D. G. Nature 298, 686–688 (1982).

    Article  ADS  CAS  Google Scholar 

  18. Anderson, S. & Kingston, B. Proc. natn. Acad. Sci. U.S.A. 80, 6838–6842 (1983).

    Article  ADS  CAS  Google Scholar 

  19. Jaye, M. et al. Nucleic Acids Res. 11, 2325–2335 (1983).

    Article  CAS  Google Scholar 

  20. Ullrich, A. et al. EMBO J. 3, 361–364 (1984).

    Article  CAS  Google Scholar 

  21. Messing, J., Crea, R. & Seeburg, P. H. Nucleic Acids Res. 9, 309–321 (1981).

    Article  CAS  Google Scholar 

  22. Lawn, R. M. et al. Cell 15, 1157–1163 (1978).

    Article  CAS  Google Scholar 

  23. Huynh, T., Young, R. & Davis, R. in Practical Approaches in Biochemistry (ed. Grover, D.) (IRL Press, Oxford, in the press).

  24. Tan, L. & Rousseau, P. Biochem. biophys. Res. Commun. 109, 1061–1071 (1982).

    Article  CAS  Google Scholar 

  25. Orihawa, S. et al. Nature 306, 611–614 (1983).

    Article  ADS  Google Scholar 

  26. Young, R. A., Hagenbuchle, O. & Schibler, U. Cell 23, 451–458 (1981).

    Article  CAS  Google Scholar 

  27. Proudfoot, N. J. & Brownlee, G. G. Nature 263, 211–214 (1976).

    Article  ADS  CAS  Google Scholar 

  28. Breathnach, R. et al. Proc. natn. Acad. Sci. U.S.A. 75, 4853–4857 (1978).

    Article  ADS  CAS  Google Scholar 

  29. Lehrach, H., Diamond, D., Wozney, J. M. & Boedtker, H. Biochemistry 16, 4743–4751 (1977).

    Article  CAS  Google Scholar 

  30. Douglass, J., Civelli, O. & Herbert, E. A. Rev. Biochem. 53, 665–750 (1984).

    Article  CAS  Google Scholar 

  31. Kozak, M. Nature 308, 241–246 (1984).

    Article  ADS  CAS  Google Scholar 

  32. Kozak, M. Nucleic Acids Res. 9, 5233–5252 (1981).

    Article  CAS  Google Scholar 

  33. Perlman, D. & Halvorson, H. O. J. molec. Biol. 167, 391–409 (1983).

    Article  CAS  Google Scholar 

  34. Land, H., Schutz, G., Schmale, H. & Richter, D. Nature 295, 299–303 (1982).

    Article  ADS  CAS  Google Scholar 

  35. Shen, L. P., Pictet, R. L. & Rutter, W. J. Proc. natn. Acad. Sci. U.S.A. 79, 4575–4579 (1982).

    Article  ADS  CAS  Google Scholar 

  36. Furutani, Y. et al. Nature 301, 539–540 (1983).

    Article  ADS  Google Scholar 

  37. Gubler, U. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4311–4314 (1983).

    Article  ADS  CAS  Google Scholar 

  38. Chauvet, M. T., Chauvet, J. & Acher, R. Eur. J. Biochem. 69, 475–485 (1976).

    Article  CAS  Google Scholar 

  39. McCann, S. M. Neuroendocrinology 31, 355–363 (1980).

    Article  CAS  Google Scholar 

  40. Southern, E. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  41. Curtis, A. & Fink, G. Endocrinology 112, 390–392 (1983).

    Article  CAS  Google Scholar 

  42. Amara, S. G. et al. Nature 248, 240–244 (1982).

    Article  ADS  Google Scholar 

  43. Kakidani, H. et al. Nature 298, 245–249 (1982).

    Article  ADS  CAS  Google Scholar 

  44. Smyth, D. G., Stein, W. H. & Moore, S. J. biol. Chem. 238, 227–234 (1963).

    CAS  PubMed  Google Scholar 

  45. Crea, R. & Horn, T. Nucleic Acids Res. 8, 2331–2348 (1980).

    Article  CAS  Google Scholar 

  46. Sherwood, N. et al. Proc. natn. Acad. Sci. U.S.A. 80, 2794–2798 (1983).

    Article  ADS  CAS  Google Scholar 

  47. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  ADS  CAS  Google Scholar 

  48. Messing, J. & Vieira, J. Gene 19, 269–276 (1982).

    Article  CAS  Google Scholar 

  49. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning, 211–217 (Cold Spring Harbor Laboratory, New York 1982).

    Google Scholar 

  50. Taylor, J. M., Illmensee, R. & Summers, J. Biochim. biophys. Acta 4, 324–330 (1976).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seeburg, P., Adelman, J. Characterization of cDNA for precursor of human luteinizing hormone releasing hormone. Nature 311, 666–668 (1984). https://doi.org/10.1038/311666a0

Download citation

  • Received:

  • Accepted:

  • Issue date:

  • DOI: https://doi.org/10.1038/311666a0

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing