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Growth Hormone-Releasing Factor Analogues with Increased Receptor Affinity

  • John J. NestorJr
  • Teresa L. Ho
  • Barbara M. DeLustro
  • Alain B. Schreiber
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

After several erroneous earlier reports, the primary sequences of a family of related proteins exhibiting growth hormone-releasing factor (GRF) properties were reported (Guillemin et al., 1982; Rivier et al., 1982). The proteins were isolated from two different human pancreatic tumors that produced clinical signs of acromegaly, and these sequences differed only in chain length [37 (Esch et al., 1983), 40 (River et al., 1982; Esch et al, 1983), or 44 (Esch et al., 1983) residues]. Further studies with cloned human cDNA (Gubler et al., 1983; Mayo et al., 1983) or protein isolated from human hypothalami (Bohlen et al., 1983; Ling et al., 1984) suggest that the hypothalamic form of hGRF corresponds to the sequence (most likely the GRF1-44-NH2) isolated from the pancreatic tumors (Guillemin et al., 1982). The shorter sequences may result from proteolysis. More recently, the sequences of GRFs (Fig. 1) were reported from the rat (Spiess et al., 1983) and several domestic species (Brazeau et al., 1984).

Keywords

Receptor Binding Affinity Growth Hormone Release Factor Human Pancreatic Tumor Binding Potency Intrinsic Agonistic Activity 
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.

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References

  1. Böhlen, P., Brazeau, P., Bloch, B., Ling, N., Gaillard, R., and Guillemin, R., 1983, Human hypo-thalamic growth hormone releasing factor (GRF): Evidence for two forms identical to tumor derived GRF-44-NH2 and GRF-40, Biochem. Biophys. Res. Commun. 114:930–936.PubMedCrossRefGoogle Scholar
  2. Brazeau, P., Böhlen, P., Esch, F., Ling, N., Wehrenberg, W. B., and Guillemin, R., 1984, Growth hormone-releasing factor from ovine and caprine hypothalamus: Isolation, sequence analysis, and total synthesis, Biochem. Biophys. Res. Commun. 125:606–614.PubMedCrossRefGoogle Scholar
  3. Coy, D. H., Murphy, W. A., Sueiras-Diaz, J., Coy, E. J., and Lance, V. A., 1985, Structure-activity studies on the N-terminal region of growth hormone releasing factor, J. Med. Chem. 28:181–185.PubMedCrossRefGoogle Scholar
  4. Epand, R. M., Epand, R. F., and Orlowski, R. C., 1985, Presence of an amphiphilic helical segment and its relationship to biological potency of calcitonin analogs, Int. J. Peptide Protein Res. 25:105–111.CrossRefGoogle Scholar
  5. Esch, F., Böhlen, P., Ling, N. C., Brazeau, P. E., Wehrenberg, W. B., and Guillemin, R., 1983, Primary structures of three human pancreas peptides with growth hormone-releasing activity, J. Biol. Chem. 258:1806–1812.PubMedGoogle Scholar
  6. Gubler, U., Monahan, J. J., Lomedico, P. T., Bhatt, R. S., Collier, K. J., Hoffman, B. J., Böhlen, P., Esch, F., Ling, N., Zeytin, F., Brazeau, P., Poonian, M. S., and Gage, L. P., 1983, Cloning and sequence analysis of cDNA for the precursor of human growth hormone-releasing factor, somatocrinin, Proc. Natl. Acad. Sci. U.S.A. 80:4311–4314.PubMedCrossRefGoogle Scholar
  7. Guillemin, R., Brazeau, P., Böhlen, P., Esch, F., Ling, N., and Wehrenberg, W. B., 1982, Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly, Science 218:585–587.PubMedCrossRefGoogle Scholar
  8. Gysin, B., and Schwyzer, R., 1984, Hydrophobic and electrostatic interactions between adrenocorti-cotropin-(l-24)-tetracosapeptide and lipid vesicles. Amphiphilic primary structures, Biochemistry 23:1811–1818.PubMedCrossRefGoogle Scholar
  9. Heiman, M. L., Nekola, M. V., Murphy, W. A., Lance, V. A., and Coy, D. H., 1985, An extremely sensitive in vitro model for elucidating structure-activity relationships of growth hormone-releasing factor analogs, Endocrinology 116:410–415.PubMedCrossRefGoogle Scholar
  10. Laburthe, M., Amiranoff, B., Bioge, N., Rouyer-Fessard, C., Tatemoto, K., and Moroder, L., 1983, Interaction of GRF with VIP receptors and stimulation of adenylate cyclase in rat and human intestinal epithelial membranes: Comparison with PHI and secretin, FEBS Lett. 159:89–92.PubMedCrossRefGoogle Scholar
  11. Lance, V. A., Murphy, W. A., Sueiras-Diaz, J., and Coy, D. H., 1984, Superactive analogs of growth hormone-releasing factor (l-29)-amide, Biochem. Biophys. Res. Commun. 119:265–272.PubMedCrossRefGoogle Scholar
  12. Ling, N., Esch, F., Böhlen, P., Brazeau, P., Wehrenberg, W. B., and Guillemin, R., 1984, Isolation, primary structure, and synthesis of human hypothalamic somatocrinin: Growth hormone-releasing factor, Proc. Natl. Acad. Sci. U.S.A. 81:4302–4306.PubMedCrossRefGoogle Scholar
  13. Mayo, K. E., Vale, W., Rivier, J., Rosenfeld, M. G., and Evans, R. M., 1983, Expression-cloning and sequence of a cDNA encoding human growth hormone-releasing factor, Nature 306:86–88.PubMedCrossRefGoogle Scholar
  14. Momany, F. A., Bowers, C. Y., Reynolds, G. A., Chang, D., Hong, A., and Newlander, K., 1981, Design, synthesis, and biological activity of peptides which release growth hormone in vitro, Endocrinology 108:31–39.PubMedCrossRefGoogle Scholar
  15. Nestor, J. J., Jr., Tahilramani, R., Ho, T. L., McRae, G. I., Vickery, B. H., and Bremner, W. J., 1983, New luteinizing hormone-releasing factor antagonists, in: PeptidesStructure and Function (V. J. Hruby and D. H. Rich, eds.), Pierce Chemical, Rockford, IL, pp. 861–864.Google Scholar
  16. Nestor, J. J., Jr., Ho, T. L., Tahilramani, R., Horner, B. L., Simpson, R. A., Jones, G. H., McRae, G. I., and Vickery, B. H., 1984, in: LHRH and Its AnalogsContraceptive and Therapeutic Applications (B. H. Vickery, J. J. Nestor, Jr., and E. S. E. Hafez, eds.), MTP Press, Lancaster, pp. 23–33.CrossRefGoogle Scholar
  17. Nestor, J. J., Jr., Newman, S. R., DeLustros, B. M., and Schreiber, A. G., 1985a, Antagonistic analogs of human transforming growth factor alpha, in: PeptidesStructure and FunctionProceedings of the Ninth American Peptide Symposium (C. M. Deber, V.J. Hruby, and K. D. Kopple, eds.), Pierce Chemical, Rockford, IL pp. 39–42.Google Scholar
  18. Nestor, J. J., Jr., Tahilramani, R., Ho, T. L., McRae, G. I., and Vickery, B. H., 1985b, Potent LHRH agonists containing NG,NG′-dialkyl-D-homoarginines, in: PeptidesStructure and FunctionProceedings of the Ninth American Peptide Symposium (C. M. Deber, V.J. Hruby, and K. D. Kopple, eds.), Pierce Chemical, Rockford, IL pp. 557–560.Google Scholar
  19. Pert, C. B., Bowie, D. L., Fong, B. T. W., and Chang, J.-K., 1976, Synthetic analogues of Met-enkephalin which resist enzymatic destruction, in: Opiates and Endogenous Opioid Peptides (H. W. Kosterlitz, ed.), North Holland, Amsterdam, New York, pp. 79–86.Google Scholar
  20. Rivier, J., Spiess, J., Thorner, M., and Vale, W., 1982, Characterization of a growth hormone-releasing factor from a human pancreatic islet tumor, Nature 300:276–278.PubMedCrossRefGoogle Scholar
  21. Schwyzer, R., Gremlich, H.-U., Gysin, B., and Sargent, D. F., 1983, Specific interactions between peptide hormones and artificial lipid membranes, in: PeptidesStructure and Function (V. J. Hruby and D. H. Rich, eds.), Pierce Chemical, Rockford, IL, pp. 657–664.Google Scholar
  22. Seifert, H., Perrin, M., Rivier, J., and Vale, W., 1985, Binding sites for growth hormone releasing factor on rat anterior pituitary cells, Nature 313:487–489.PubMedCrossRefGoogle Scholar
  23. Spiess, J., Rivier, J., and Vale, W., 1983, Characterization of rat hypothalamic growth hormone-releasing factor, Nature 303:532–535.PubMedCrossRefGoogle Scholar
  24. Vale, W., Grant, G., Amoss, M., Blackwell, R., and Guillemin, R., 1972, Culture of enzymatically dispersed anterior pituitary cells: Functional validaton of a method, Endocrinology 91:562–572.PubMedCrossRefGoogle Scholar
  25. Zeytin, F. N., Reyl-Desmares, F., and Rathbun, T., 1985, Rat hypothalamic GRF elicits its biologic action in GH3 cells by interaction with VIP preferring receptor sites, Biochem. Biophys. Res. Commun. 127:992–998.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • John J. NestorJr
    • 1
  • Teresa L. Ho
    • 1
  • Barbara M. DeLustro
    • 1
  • Alain B. Schreiber
    • 1
  1. 1.Institutes of Bio-Organic Chemistry and Biological SciencesSyntex ResearchPalo AltoUSA

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