Endocrine, Gastrointestinal, and Antitumor Activity of Somatostatin Analogues

  • Andrew V. Schally
  • Ren-Zhi Cai
  • I. Torres-Aleman
  • Tommie W. Redding
  • Balazs Szoke
  • Dadin Fu
  • Marion T. Hierowski
  • John Colaluca
  • Stanislaw Konturek
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Since recent studies with somatostatin were carefully reviewed by Reichlin (1983) and by a variety of authors in the 2nd International Symposium on Somatostatin, which was held in Athens in 1981 but published with updates in 1984 (Raptis et al., 1984), no attempts are made to cover new developments with somatostatin-14 and somatostatin-28. Instead, this chapter focuses on the recent work in the field of somatostatin analogues and the investigations of their endocrine, gastrointestinal, and antitumor activities.


Growth Hormone Pituitary Tumor Vasoactive Intestinal Polypeptide Pancreatic Secretion Epidermal Growth Factor Binding 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adrian, T. E., Barnes, A. J., Long, R. G., O’Shaughnessy, D. J., Brown, M. R., Rivier, J., Vale, W., Blackburn, A. M., and Bloom, S. R., 1981, The effect of somatostatin analogs on secretion of growth, pancreatic, and gastrointestinal hormones in man, J. Clin. Endocrol. Metab. 53:675–681.CrossRefGoogle Scholar
  2. Bauer, W., Briner, U., Doepfner, W., Haller, R., Huguenin, R., Marbach, P., Petcher, T. J., and Pless, J., 1982, SMS-201-995: A very potent and selective octapeptide analogue of somatostatin with prolonged action, Life Sci. 31:1133–1140.PubMedCrossRefGoogle Scholar
  3. Bloom, S. R., Thorner, M. O., Besser, G. M., Hall, R., Gomez-Pan, A., Roy, V. M., Russell, R. C. G., Coy, D. H., Kastin, A. J., and Schally, A. V., 1974, Inhibition of gastrin and gastric-acid secretion by growth-hormone release-inhibiting hormone, Lancet 2:1106.PubMedCrossRefGoogle Scholar
  4. Brown, M. E., Rivier, J. E., and Vale, W. W., 1977, Somatostatin analogs with selected biological activities, Science 196:1467–1468.PubMedCrossRefGoogle Scholar
  5. Brown, M. P., Coy, D. H., Gomez-Pan, A., Hirst, B. H., Hunter, M., Meyers, C., Reed, J. D., Schally, A. V., and Shaw, B., 1978, Structure-activity relationships of eighteen somatostatin analogues on gastric secretion, J. Physiol. (Lond.) 277:1–14.Google Scholar
  6. Cai, R.-Z., Szoke, B., Fu, D., Redding, T. W., Colaluca, J., Torres-Aleman, I., and Schally, A. V., 1986, in: Proceedings of the Ninth American Peptide Symposium June 1985 (V. J. Hruby, K. D. Kopple, and C. M. Deber, eds.), Pierce Chemical Co., Rockford, II, pp. 627–630.Google Scholar
  7. Charro, A. L., Cabranes, J. A., Lafuente, A., Diaz-Salgado, C., Cordero, M., Almoguera, E., Comaru-Schally, A. M., Meyers, C. A., Coy, D. H., and Schally, A. V., 1984, Inhibition of growth hormone and glucagon release by Phe-4-somatostatin in patients with acromegaly, Res. Commun. Chem. Pathol. Pharmacol. 45:432–444.PubMedGoogle Scholar
  8. Dembinski, A. B., and Johnson, L. R., 1980, Stimulation of pancreatic growth by secretin, caerulein, and pentagastrin, Endocrinology 106:323–328.PubMedCrossRefGoogle Scholar
  9. De Quijada, M. G., Redding, T. W., Coy, D. H., Torres-Aleman, I., and Schally, A. V., 1983, Inhibition of growth of a prolactin-secreting pituitary tumor in rats by analogs of luteinizing hormone-releasing hormone and somatostatin, Proc. Natl. Acad. Sci. U.S.A. 80:3485–3488.PubMedCrossRefGoogle Scholar
  10. Dollinger, H. C., Raptis, S., and Pfeiffer, E. F., 1976, Effects of somatostatin on exocrine and endocrine pancreatic function stimulated by intestinal hormones in man, Horm. Metab. Res. 8:74–78.PubMedCrossRefGoogle Scholar
  11. Downward, J., Yarden, Y., Mayes, E., Scrace, G., Totty, N., Stockwell, P., Ullrich, A., Schlessinger, J., and Waterfield, M. D., 1984, Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences, Nature 307:521–527.PubMedCrossRefGoogle Scholar
  12. Gibbs, J., Young, R. C., and Smith, G. P., 1973, Cholecystokinin elicits satiety in rats with open gastric fistulas, Nature 245:323–325.PubMedCrossRefGoogle Scholar
  13. Gonzalez-Barcena, D., Mendoza, F., Medina, R., Coy, D. H., Murphy, W. A., and Schally, A. V., 1984, Effect of Ala-2-D-Trp-8-D-Cys-14-somatostatin on the arginine induced release of insulin, GH and glucagon in normal men, Endocrine Res. 10:39–48.Google Scholar
  14. Gottesman, E. S., Mandarino, L. J., and Gerich, J. E., 1982, Somatostatin, in: Special Topics in Endocrinology and Metabolism, Vol. 4 (M. Cohen, ed.), Alan R. Liss, New York, pp. 177–243.Google Scholar
  15. Grant, N., Clark, D., Garsky, V., Juanakais, E., McGregor, W., and Sarantakis, D., 1976, Dissociation of somatostatin effects. Peptides inhibiting the release of growth hormone but not glucagon or insulin in rats, Life Sci. 19:629–632.PubMedCrossRefGoogle Scholar
  16. Hall, R., and Gomez-Pan, A., 1976, The hypothalamic regulatory hormones and their clinical applications, Adv. Clin. Chem. 18:173–212.PubMedCrossRefGoogle Scholar
  17. Heldin, C.-H., and Westermark, B., 1984, Growth factors: Mechanism of action and relation to on-cogenes, Cell 37:9–20.PubMedCrossRefGoogle Scholar
  18. Hierowski, M. T., Liebow, C., du Sapin, K., and Schally, A. V., 1985, Stimulation by somatostatin of dephosphorylation of membrane proteins in pancreatic cancer MIA PaCa-2 cell line, FEBS Lett. 179:252–256.PubMedCrossRefGoogle Scholar
  19. Hirst, B. H., Shaw, B., Meyers, C. A., and Coy, D. H., 1980, Structure-activity studies with somatostatin: The role of tryptophan in position 8, Regul. Peptides 1:97–113.CrossRefGoogle Scholar
  20. Hirst, B. H., Arilla, E., Coy, D. H., and Shaw, B., 1984, Cyclic hexa-and pentapeptide somatostatin analogues with reduced gastric inhibitory activity, Peptides 5:857–860.PubMedCrossRefGoogle Scholar
  21. Konturek, S. J., Tasler, J., Krol, R., Dembinski, A., Coy, D. H., and Schally, A. V., 1977, Effect of somatostatin analogs on gastric and pancreatic secretion, Proc. Soc. Exp. Biol. Med. 155:519–522.PubMedGoogle Scholar
  22. Konturek, S. J., Cieszkowski, M., Bilski, J., Konturek, J., Bielanski, W., and Schally, A. V., 1985, Effects of cyclic hexapeptide analog of somatostatin on pancreatic secretion in dogs, Proc. Soc. Exp. Biol. Med. 178:68–72.PubMedGoogle Scholar
  23. Kraenzlin, M. E., Ch’ng, J. C., Wood, S. M., and Bloom, S. R., 1983, Can inhibition of hormone secretion be associated with endocrine tumour shrinkage? Lancet 2:1501.PubMedCrossRefGoogle Scholar
  24. Kraenzlin, M. E., Ch’ng, J. L. C., Wood, S. M., and Bloom, S. R., 1984, Remission of symptoms and shrinkage of metastasis with long term treatment with somatostatin analogue, Gut 25:A576.Google Scholar
  25. Lamberts, S. W. J., Uitterlinden, P., Zuiderwijk, J., Verleun, T., Neufeld, M., and Del Pozo, E., 1984, The effects of a long-acting somatostatin analog on pituitary tumor growth and hormone secretion in rat and man, Excerpta Med. 652:847.Google Scholar
  26. Long, R. G., Barnes, A. J., Adrian, T. E., Mallinson, C. N., Brown, M. R., Vale, W., Rivier, J. E., Christopides, N. D., and Bloom, S. R., 1979, Suppression of pancreatic endocrine tumour secretion by long-acting somatostatin analogue, Lancet 2:764–767.PubMedCrossRefGoogle Scholar
  27. Marbach, M., Neufeld, M., and Pless, J., 1984, Clinical applications of somatostatin analogs, in: Proceedings of the Symposium on Somatostatin, Montreal, July 1984 (Y. C. Patel and G. S. Tannenbaum, eds.), Elsevier, Amsterdam, pp. 339–345.Google Scholar
  28. Mascardo, R. N., and Sherline, P., 1982, Somatostatin inhibits rapid centrosomal separation and cell proliferation induced by epidermal growth factor, Endocrinology 111:1394–1396.PubMedCrossRefGoogle Scholar
  29. Maton, P. N., O’Dorisio, T. M., Howe, B. A., McArthur, K. E., Howard, J. M., Cherner, J. A., Malarkey, T. B., Collen, M. J., Gardner, J. D., and Jensen, R. T., 1985, Effect of a long-acting somatostatin analogue (SMS 201–995) in a patient with pancreatic cholera, N. Engl. J. Med. 312:17–21.PubMedCrossRefGoogle Scholar
  30. McCumbee, W. D., McCarty, D. S., Jr., and Lebovitz, H. E., 1980, Hormone responsiveness of a transplantable rat chondrosarcoma. II. Evidence for in vivo hormone dependence, Endocrinology 106:1930–1940.PubMedCrossRefGoogle Scholar
  31. Merrifield, R. B., 1967, Solid phase peptide synthesis. III. An improved synthesis of bradykinin, Recent Prog. Horm. Res. 23:451–482.PubMedGoogle Scholar
  32. Meyers, C., Arimura, A., Gordin, A., Fernandez-Durango, R., Coy, D. H., Schally, A. V., Drouin, J., Ferland, L., Beaulieu, M., and Labrie, F., 1977, Somatostatin analogs which inhibit glucagon and growth hormone more than insulin release, Biochem. Biophys. Res. Commun. 74:630–636.PubMedCrossRefGoogle Scholar
  33. Meyers, C. A., Coy, D. H., Huang, W. Y., Schally, A. V., and Redding, T. W., 1978, Highly active position eight analogues of somatostatin and separation of peptide diastereomers by partition chro-matography, Biochemistry 17:2326–2331.PubMedCrossRefGoogle Scholar
  34. Mortimer, C. H., Tunbridge, W. M. G., Carr, D., Yeomans, L., Lind, T., Coy, D. H., Bloom, S. R., Kastin, A., Mallinson, C. N., Besser, G. M., Schally, A. V., and Hall, R., 1974, Effects of growth-hormone release-inhibiting hormone on circulating glucagon, insulin, and growth hormone in normal, diabetic, acromegalic, and hypo-pituitary patients, Lancet 1:697–701.PubMedCrossRefGoogle Scholar
  35. Pfeiffer, E. F., and Schusdziarra, V., 1984, What can a clinician extract from the development of somatostatin for therapy? in: 2nd International Symposium on Somatostatin, Athens (Greece) (S. Raptis, J. Rosenthal, and J. E. Gerich, eds.), Attempto Verlag, Tübingen, pp. 222–231.Google Scholar
  36. Plewe, G., Beyer, J., Krause, U., Neufeld, M., and Del Pozo, E., 1984, Long-acting and selective suppression of growth hormone secretion by somatostatin analogue SMS 201–995 in acromegaly, Lancet 2:782–784.PubMedCrossRefGoogle Scholar
  37. Raptis, S., Rosenthal, J., and Gerich, J. E., eds., 1984, 2nd International Symposium on Somatostatin, Athens (Greece), Attempto Verlag, Tübingen.Google Scholar
  38. Redding, T. W., and Schally, A. V., 1983, Inhibition of growth of the transplantable rat chondrosarcoma by analogs of hypothalamic hormones, Proc. Natl. Acad. Sci. U.S.A. 80:1078–1082.PubMedCrossRefGoogle Scholar
  39. Redding, T. W., and Schally, A. V., 1984, Inhibition of growth of pancreatic carcinomas in animal models by analogs of hypothalamic hormones, Proc. Natl. Acad. Sci. U.S.A. 81:248–252.PubMedCrossRefGoogle Scholar
  40. Redding, T. W., Schally, A. V., Tice, T. R., and Meyers, W. E., 1984, Long-acting delivery systems for peptides: Inhibition of rat prostate tumors by controlled release of [D-Trp-6]luteinizing hormone-releasing hormone from injectable microcapsules, Proc. Natl. Acad. Sci. U.S.A. 81:5845–5848.PubMedCrossRefGoogle Scholar
  41. Reichlin, S., 1983, Somatostatin, N. Engl. J. Med. 309:1495–1501, 1556–1563.PubMedCrossRefGoogle Scholar
  42. Rivier, J., Brown, M., and Vale, W., 1975, D-Trp-8-Somatostatin: An analog of somatostatin more potent than the native molecule, Biochem. Biophys. Res. Commun. 65:746–751.PubMedCrossRefGoogle Scholar
  43. Rivier, J., Brown, M., Rivier, C., Ling, N., and Vale, W., 1977, Hypothalamic hypophysiotropic hormones. Review on the design of synthetic analogs, in: Peptides 1976 (A. Loffet, ed.), l’Université de Bruxelles, Brussels, pp. 427–449.Google Scholar
  44. Rose, D. P., Gottardis, M., and Noonan, J. J., 1983, Rat mammary carcinoma regressions during suppression of serum growth hormone and prolactin, Anticancer Res. 3:323–326.PubMedGoogle Scholar
  45. Salomon, D. S., Paglia, L. M., and Verbruggen, L., 1979, Hormone-dependent growth of a rat chondrosarcoma in vivo, Cancer Res. 39:4387–4395.PubMedGoogle Scholar
  46. Schally, A. V., Coy, D. H., and Meyers, C. A., 1978, Hypothalamic regulatory hormones, Annu. Rev. Biochem. 47:89–128.PubMedCrossRefGoogle Scholar
  47. Schally, A. V., Comaru-Schally, A. M., and Redding, T. W., 1984a, Antitumor effects of analogs of hypothalamic hormones in endocrine-dependent cancers, Proc. Soc. Exp. Biol. Med. 175:259–281.PubMedGoogle Scholar
  48. Schally, A. V., Coy, D. H., Murphy, W. A., Redding, T. W., Comaru-Schally, A. M., Hall, R., Rodriguez-Arnao, M. D., Gomez-Pan, A., Gonzalez-Barcena, D., Millar, R. P., and Konturek, S., 1984b, Physiological and clinical studies with somatostatin analogs and pro-somatostatin, in: 2nd International Symposium on Somatostatin, Athens (Greece) (S. Raptis, J. Rosenthal, and J. E. Gerich, eds.), Attempto Verlag, Tübingen, pp. 188–196.Google Scholar
  49. Schally, A. V., Redding, T. W., and Comaru-Schally, A. M., 1984c, Potential use of analogs of luteinizing hormone-releasing hormones in the treatment of hormone-sensitive neoplasms, Cancer Treat. Rep. 68:281–289.PubMedGoogle Scholar
  50. Snodgrass, P. J., 1977, Section 7, Disorders of the pancreas, in: Harrison’s Principles of Internal Medicine, 8th ed. (G. W. Thorn, R. D. Adams, E. Braunwald, K. J. Isselbacher, and R. G. Petersdorf, eds.), McGraw-Hill, New York, pp. 1643–1645.Google Scholar
  51. Szilagyi, G., Irsy, G., Goth, M., Szabolcs, I., Coy, D. H., Comaru-Schally, A. M., and Schally, A. V., 1984, Effect of a somatostatin analogue on trophic hormone levels in acromegalic patients with elevated hGH after adrenomectomy and treatment with bromocriptine, Exp. Clin. Endocrinol. 84:190–196.PubMedCrossRefGoogle Scholar
  52. Torres-Aleman, I., Redding, T. W., and Schally, A. V., 1985, Inhibition of growth of a prolactin and growth hormone-secreting pituitary tumor in rats by D-tryptophan-6 analog of luteinizing hormone-releasing hormone, Proc. Natl. Acad. Sci. U.S.A. 82:1252–1256.PubMedCrossRefGoogle Scholar
  53. Townsend, C. M., Jr., Franklin, R. B., Watson, L. C., Glass, E. J., and Thompson, J. C., 1981, Stimulation of pancreatic cancer growth by caerulein and secretin, Surg. Forum 34:228–229.Google Scholar
  54. Usadel, K. H., Leuschner, U., and Uberla, K. K., 1980, Treatment of acute pancreatitis with somatostatin: A multicenter double-blind trial, N. Engl. J. Med. 303:999–1000.PubMedCrossRefGoogle Scholar
  55. Usadel, K. H., Leuschner, U., and Uberla, K. K., 1984, Report on a randomized double-blind European multicenter study on the use of somatostatin in acute pancreatitis (APTS) in: 2nd International Symposium on Somatostatin, Athens (Greece) (S. Raptis, J. Rosenthal, and J. E. Gerich, eds.), Attempto Verlag, Tübingen, pp. 236–243.Google Scholar
  56. Veber, D. F., Holly, F. W., Nutt, R. F., Bergstrand, S. J., Brady, St. F., Hirschmann, R., Glitzer, M. S., and Saperstein, R., 1979, Highly active cyclic and bicyclic somatostatin analogs of reduced ring size, Nature 280:512–514.PubMedCrossRefGoogle Scholar
  57. Veber, D. F., Freidinger, R. M., Schwenk-Perlow, D., Paleveda, W. J., Jr., Holly, R. W., Strachan, R. G., Nutt, R. F., Arison, B. H., Homnick, C., Randall, W. C., Glitzer, M. S., Saperstein, R., and Hirschmann, R., 1981, A potent cyclic hexapeptide analogue of somatostatin, Nature 292:55–58.PubMedCrossRefGoogle Scholar
  58. Veber, D. F., Saperstein, R., Nutt, R. F., Freidinger, R. M., Brady, S. F., Curley, P., Perlow, D. S., Paleveda, W. J., Colton, C. D., Zacchei, A. G., Tocco, D. J., Hoff, D. R., Vandlen, R. L., Gerich, J. E., Hall, L., Mandarino, L., Cordes, E. H., Anderson, P. S., and Hirschmann, R., 1984, A super active cyclic hexapeptide analog of somatostatin, Life Sci. 34:1371–1378.PubMedCrossRefGoogle Scholar
  59. Von Werder, K., Losa, M., Müller, O. A., Schweiberer, L., Falhbusch, R., and Del Pozo, E., 1984, Treatment of metastasising GRF-producing tumour with a long-acting somatostatin analogue, Lancet 2:282–283.CrossRefGoogle Scholar
  60. Wajchenberg, B. L., Cesar, F. P., Lerne, C. E., Borghi, V. C., Souza, I. T. T., Neto, D. G., Germek, O. A., Coy, D. H., Comaru-Schally, A. M., and Schally, A. V., 1983, Dissociated effects of somatostatin analogs on arginine-induced insulin, glucagon and growth hormone release in acromegalic patients, Horm. Metab. Res. 15:471–474.PubMedCrossRefGoogle Scholar
  61. Yamamoto, T., Nishida, T., Miyajima, N., Kawai, S., Ooi, T., and Toyoshima, K., 1983, The erbB gene of avian erythroblastosis virus is a member of the sre gene family, Cell 35:71–78.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Andrew V. Schally
    • 1
  • Ren-Zhi Cai
    • 1
  • I. Torres-Aleman
    • 1
  • Tommie W. Redding
    • 1
  • Balazs Szoke
    • 1
  • Dadin Fu
    • 1
  • Marion T. Hierowski
    • 1
  • John Colaluca
    • 1
  • Stanislaw Konturek
    • 2
  1. 1.Veterans Administration Medical CenterTulane University School of MedicineNew OrleansUSA
  2. 2.Medical AcademyKrakowPoland

Personalised recommendations