Advertisement

Somatostatin pp 325-337 | Cite as

Somatostatin Agonists and Antagonists - Peptide Control of Growth Hormone Secretion

  • David H. Coy
  • William A. Murphy
  • Valentine A. Lance
  • Simon J. Hocart
  • Javier Sueiras-Diaz
  • Irme Mezo
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 188)

Abstract

Although somatostatin itself has numerous inhibitory activities which individually are of no little therapeutic interest, there are also several types of physiological effects where it might be of even greater basic and medical value to block activity instead. Perhaps principal among these would be an ability to block the inhibitory effects of somatostatin on growth hormone (GH) release. Antibody experiments (1) have clearly shown that basal GH levels are elevated when somatostatin is neutralized. There is also an unwanted negative participation of somatostatin when GH levels are stimulated with the GH-releasing factor, GRF. In fact, one group has actually been able to demonstrate that GRF(1–44) stimulates somatostatin release from hypothalamic cells in culture (2). It should also be mentioned that both GH (3) and somatostatin (4) can alter somatostatin levels. Somatomedin C has also been implicated in the negative feedback regulation of GH, at least partially by stimulating release of somatostatin (5). Given the successes which have been achieved in the development of very potent competitive antagonists of other peptides, notably in our own experience with LH-RH, there appears to be no reason to neglect the development of a somatostatin antagonist any longer.

Keywords

Growth Hormone Growth Hormone Level Growth Hormone Release Glucagon Release Plasma Growth Hormone Level 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Oliver C, Giraud P, Lissitzky JC, Cote J, Boudouresque F, Gillioz P, Conte-Devolx B 1982 Influence of endogenous somatostatin on GH and TSH secretion in neonatal rats. Endocrinology 110: 1018.PubMedCrossRefGoogle Scholar
  2. 2.
    Iwasaki K, Arimura A, Stimulation of somatostatin release by hpGRF-44 from rat hypothalamic cells and fragments in vitro. Program of the 7th International Congress of Endocrinology. Quebec City, July 1984, A963 (Abstract).Google Scholar
  3. 3.
    Berelowitz M, Firestone SL, Frohman LA 1981 Effects of GH excess and deficiency on hypothalamic somatostatin content and release and on tissue somatostatin distribution. Endocrinology 109: 714.PubMedCrossRefGoogle Scholar
  4. 4.
    Lumpkin MD, Negro-Vilar A, McCann SM 1981 Paradoxical elevation of GH by intraventricular somatostatin: possible ultra short-loop feedback. Science 211: 1072.PubMedCrossRefGoogle Scholar
  5. 5.
    Abe A, Molitch ME, Van Wyk JJ, Underwood LE 1983 Human GH and somatomedin C suppress the spontaneous release of GH in un-anesthetized rats. Endocrinology 113: 1319.PubMedCrossRefGoogle Scholar
  6. 6.
    Veber DF, Holly FW, Nutt RF, Bergstrand SJ, Brady SF, Hirschmann R, Glitzer MS, Saperstein RS 1979 Highly active cyclic and bicyclic somatostatin analogues of reduced ring size. Nature 280: 512.PubMedCrossRefGoogle Scholar
  7. 7.
    Fries JL, Murphy WA, Sueiras-Diaz JA, Coy DH 1982 Somatostatin antagonist analog increases GH, insulin and glucagon release in the rat. Peptides 3: 811.PubMedCrossRefGoogle Scholar
  8. 8.
    Veber DF, Friedinger RM, Perlow DS, Palaveda WJ, Holly FW, Strachan RG, Nutt RF, Arison BH, Homnick C, Randall WC, Glitzer MS, Saperstein R, Hirschmann R 1981 A potent cyclic hexapeptide analogue of somatostatin. Nature 292: 55.PubMedCrossRefGoogle Scholar
  9. 9.
    Rivier J, Brown M, Rivier C, Ling N, Vale W 1976 Hypothalamic hypophysiotropic hormones. In: Loffet A (ed) Peptides. Editions de l’Université de Bruxelles, Brussels, p 427.Google Scholar
  10. 10.
    Meyers C, Arimura A, Gordon A, Fernandez R, Coy DH, Schally AV, Drouin L, Ferland M, Beaulieu M, Labrie F 1977 Somatostatin analogs which inhibit glucagon and GH more than insulin release. Biochem Biophys Res Commun 74: 630.PubMedCrossRefGoogle Scholar
  11. 11.
    Lance VA, Murphy WA, Sueiras-Diaz JA, Coy DH 1984 Super-active analogs of growth hormone-releasing factor(1–29) amide. Biochem Biophys Res Commun 119: 265.PubMedCrossRefGoogle Scholar
  12. 12.
    Coy DH, Murphy WA, Sueiras-Diaz JA, Coy EJ, Lance VA 1984 Structure-activity studies on the N-terminal region of growth hormone releasing factor. J Med Chem, in press.Google Scholar
  13. 13.
    Heiman ML, Nekola MV, Lance VA, Murphy WA, Coy DH, Potency of GRF agonists stimulating GH release from cultured pituitary cells correlates with binding to a putative GRF receptor. Program of the 7th International Congress of Endocrinology. Quebec City, July 1984, A956 (Abstract).Google Scholar
  14. 14.
    Robberecht P, Coy DH, Waelbroeck M, de Neef P, Camus J-C, Christophe J 1984 Structural requirements for the activation of rat anterior pituitary adenylate cyclase by GRF - discovery of [N-Ac-Tyr-1, D-Arg-2]-GRF(1–29)NH2 as a GRF antagonist. Endocrinology, in press.Google Scholar
  15. 15.
    Waelbroeck M, Robberecht P, Coy DH, Camus J-C, de Neef P, Christophe J 1985 Interaction of GRF and 14 GRF analogs with rat pancreatic VIP receptors. Discovery of [N-Ac-Tyr-1,D-Phe-2] -GRF(1–29)NH2 as a VIP antagonist. Endocrinology (in press).Google Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • David H. Coy
    • 1
  • William A. Murphy
    • 1
  • Valentine A. Lance
    • 1
  • Simon J. Hocart
    • 1
  • Javier Sueiras-Diaz
    • 1
  • Irme Mezo
    • 1
  1. 1.Section of Endocrinology and Metabolism, Department of MedicineTulane University School of MedicineNew OrleansUSA

Personalised recommendations