Abstract
Relaxin is a peptide hormone1–4 synthesized in the corpora lutea of ovaries during pregnancy and is released into the blood stream prior to parturition. Its major biological effect is to remodel the mammalian reproductive tract to facilitate the birth process5. Determination of the structure of human relaxin is thus a first step in opening up the possibility of clinical intervention in cases of difficult labour. However, the limited availability of human ovaries during pregnancy has prevented both direct amino acid sequence determination and isolation of cDNA clones obtained from relaxin producing tissue. Our approach has therefore been to screen directly for a human relaxin gene using an homologous porcine relaxin cDNA probe. We report here the successful identification of a genomic clone from which the structure of the entire coding region of a human preprorelaxin gene has been determined. Synthesis of biologically active relaxin has shown that the novel gene structure described herein codes for an authentic human relaxin. We believe this is the first successful synthesis of a biologically active hormone whose structure was predicted solely from the structure of a genomic clone.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Schwabe, C., McDonald, J. K. & Steinetz, B. G. Biochem. biophys. Res. Commun. 75, 503–510 (1977).
James, R., Niall, H., Kwok, S. & Bryant-Greenwood, G. Nature 267, 544–546 (1977).
John, M. J., Borjesson, B. W., Walsh, J. R. & Niall, H. D. Endocrinology 108, 726–729 (1981).
Schwabe, C., Gowan, L. K. & Reinig, J. W. Ann. N.Y. Acad. Sci. 380, 6–12 (1982).
Porter, D. G. Biol. Reprod. 7, 458–465 (1972).
Hudson, P., Haley, J., Cronk, M., Shine, J. & Niall, H. Nature 291, 127–131 (1981).
Haley, J. et al. DNA 1, 155–162 (1982).
Chan, S. J., Keim, P. & Steiner, D. F. Proc. natn. Acad. Sci. U.S.A. 73, 1964–1968 (1976).
Lawn, R. M., Fritsch, E. F., Parker, R. C., Blake, G. & Maniatis, T. Cell 15, 1157–1174 (1978).
Maniatis, T. et al. Cell 15, 687–701 (1978).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).
Bell, G. I. et al. Nature 284, 26–32 (1980).
Steiner, D. F., Quinn, P. S., Chan, S. J., Marsh, J. & Tager, H. S. Ann. N.Y. Acad. Sci. 343, 1–16 (1980).
Tregear, G. et al. in Peptides: Synthesis, Structure, Function (eds Rich, D. H. & Gross, E.) 249–252 (Pierce Chemical Co., Rockville, Illinois, 1981).
Bedarkar, S., Turnell, W. G., Blundell, T. L. & Schwabe, C. Nature 270, 449–451 (1977).
Isaacs, N. et al. Nature 271, 278–281 (1978).
Hirs, C. H. W., Moore, S. & Stein, W. H. J. biol. Chem. 219, 623–630 (1956).
Light, A. Meth. Enzym. 11, 426–436 (1967).
Du, Y-C., Minasian, E., Tregear, G. W. & Leach, S. J. Int. J. Peptide Protein Res. 20, 47–54 (1982).
Wiqvist, N. & Paul, K. G. Acta endocr. 29, 135–136 (1958).
Bryant-Greenwood, G. D., Jeffrey, R., Ralph, M. M. & Seamark, R. F. Biol. Reprod. 23, 792–798 (1980).
Weib, M., Magelschmidt, M. & Struck, H. Horm. Metab. Res. 11, 408–410 (1979).
Stone, M. L., Sedlis, A. & Zuckerman, M. B. Ann N.Y. Acad. Sci. 75, 1011–1015 (1959).
Chihal, H. J. & Epsey, L. L. Endocrinology 93, 1441–1445 (1973).
Loumaye, E., Decooman, S. & Thomas, K. J. Clin. Endocr. Metab. 50, 1142–1143 (1980).
Hisaw, F. L., Hisaw, F. L. Jr & Alden, D. B. Endocrinology 81, 375–385 (1967).
Taylor, J. M., Illmensee, R. & Summers, J. Biochim. biophys Acta 442, 324–330 (1976).
Benton, W. D. & Davis, R. W. Science 196, 180–182 (1977).
Denhardt, D. T. Biochem. biophys. Res. Commun. 23, 641–646 (1966).
Yamamoto, K. R., Alberts, B. M., Benzinger, R., Lawhorne, L. & Treiber, G. Virology 40, 734–744 (1970).
Sanger, F., Coulson, A. R., Barrell, B. G., Smith, A. J. H. & Roe, B. A. J. molec. Biol. 143, 161–178 (1980).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
Beaucage, S. L. & Caruthers, M. H. Tetrahedron Lett. 22, 1859–1862 (1981).
Chance, R. E. & Hoffmann, J. A., Australian Patent Appl. No. 68844/81.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hudson, P., Haley, J., John, M. et al. Structure of a genomic clone encoding biologically active human relaxin. Nature 301, 628–631 (1983). https://doi.org/10.1038/301628a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/301628a0
This article is cited by
-
Production of human pro-relaxin H2 in the yeast Pichia pastoris
BMC Biotechnology (2017)
-
Application of the novel bioluminescent ligand–receptor binding assay to relaxin-RXFP1 system for interaction studies
Amino Acids (2016)
-
Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and post-release action of the insulin-like peptides
Cellular and Molecular Life Sciences (2016)
-
Recombinant Human Relaxin-2: (How) Can a Pregnancy Hormone Save Lives in Acute Heart Failure?
American Journal of Cardiovascular Drugs (2014)
-
Cardiovascular effects of relaxin: from basic science to clinical therapy
Nature Reviews Cardiology (2010)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
