Somatostatin pp 121-135 | Cite as

Mechanisms by which Somatostatin Inhibits Pituitary Hormone Release

  • Agnes Schonbrunn
  • Bruce D. Koch
Part of the Serono Symposia, USA book series (SERONOSYMP)


Since somatostatin inhibits secretion in a wide variety of target cells, studies probing its mechanism of action have focused on the involvement of the two intracellular messengers known to regulate secretory processes: cyclic AMP and calcium (see reviews 1–5).


Adenylate Cyclase Pituitary Cell Pertussis Toxin Guanine Nucleotide Binding Protein Growth Hormone Cell 
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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  1. 1.
    Reichlin S. Somatostatin. N Engl J Med 1983; 309:1495 and 1556.PubMedCrossRefGoogle Scholar
  2. 2.
    Gottesman IS, Mandarino LJ, Gerich JE. Somatostatin: its role in health and disease. In: Cohen MP, Foa PP, eds. Special topics in endocrinology and metabolism, vol 4. New York: Alan R. Liss Inc., 1982: 177.Google Scholar
  3. 3.
    Pace CS. Somatostatin: control of stimulus-secretion coupling in pancreatic islet cells. In: Bloom FE, ed. Peptides: integrators of cell and tissue function. New York: Raven Press, 1980: 163.Google Scholar
  4. 4.
    Schonbrunn A, Dorf linger LJ, Koch BD. Mechanisms of somatostatin action in pituitary cells. In: Patel Y, Tannenbaum G, eds. Somatostatin. New York: Plenum Press, 1985: 305.Google Scholar
  5. 5.
    Patel YC, Srikant CB. Somatostatin mediation of adenohypophysfal secretion. Annu Rev Physiol 1986; 48: 551.PubMedCrossRefGoogle Scholar
  6. 6.
    Vale W, Rivier C, Brazeau P, Guillemin R. Effects of somatostatin on the secretion of thyrotropin and prolactin. Endocrinology 1974; 95: 968.PubMedCrossRefGoogle Scholar
  7. 7.
    Drouin J, De Lean A, Rainville D, Lachance R, Labrie F. Characteristics of the interaction between thyrotropin-releasing hormone and somatostatin for thyrotropin and prolactin release. Endocrinology 1976; 98: 514.PubMedCrossRefGoogle Scholar
  8. 8.
    Enjalbert A, Epelbaum J, Arancibia S, Tapia-Arancibia L, Blute-Pajot M-T, Kordon C. Reciprocal interactions of somatostatin with thyrotropin-releasing hormone and vasoactive intestinal peptide on prolactin and growth hormone secretion in vitro. Endocrinology 1982; 111: 42.PubMedCrossRefGoogle Scholar
  9. 9.
    Cooper GR, Shin SH. Somatostatin inhibits prolactin secretion in the estradiol primed male rat. Can J Physiol 1981; 59: 1082.CrossRefGoogle Scholar
  10. 10.
    Schonbrunn A, Tashjian AH Jr. Characterization of functional receptors for somatostatin in rat pituitary cells in culture. J Biol Chem 1978; 253: 6473.PubMedGoogle Scholar
  11. 11.
    Dorflinger LJ, Schonbrunn A. Somatostatin inhibits basal and vaso-active intestinal peptide stimulated hormone release by different mechanisms in GH pituitary cells. Endocrinology 1983; 113: 1551.PubMedCrossRefGoogle Scholar
  12. 12.
    Westendorf JM, Schonbrunn A. Bombesin stimulates prolactin and growth hormone release by pituitary cells in culture. Endocrinology 1982; 110: 352.PubMedCrossRefGoogle Scholar
  13. 13.
    Dorf linger LJ, Schonbrunn A. Somatostatin inhibits vasoactive intestinal peptide-stimulated cyclic adenosine monophosphate accumulation in GH pituitary cells. Endocrinology 1983, 113: 1541.PubMedCrossRefGoogle Scholar
  14. 14.
    Gershengorn MC. Mechanism of thyrotropin releasing hormone stimulation of pituitary hormone secretion. Annu Rev Physiol 1986; 48: 515.PubMedCrossRefGoogle Scholar
  15. 15.
    Williams JA. Regulatory mechanisms in pancreas and salivary acini. Annu Rev Physiol 1984; 46: 361.PubMedCrossRefGoogle Scholar
  16. 16.
    Sutton CA, Martin TFJ. Thyrotropin releasing hormone (TRH) selectively and rapidly stimulates phosphatidylinositol turnover in GH pituitary cells: a possible second step of TRH action. Endocrinology 1982; 110: 1273.PubMedCrossRefGoogle Scholar
  17. 17.
    Schonbrunn A, Rorstad OP, Westendorf JM, Martin JB. Somatostatin analogs: correlation between receptor binding affinity and biological potency in GH pituitary cells. Endocrinology 1983; 113: 1559.PubMedCrossRefGoogle Scholar
  18. 18.
    Presky DH, Schonbrunn A. Receptor-bound somatostatin and epidermal growth factor are processed differently in GH4C1 rat pituitary cells. J Cell Biol 1986; 102: 878.PubMedCrossRefGoogle Scholar
  19. 19.
    Dannies PS, Gautvik KM, Tashjian AH Jr. A possible role of cyclic AMP in mediating the effects of thyrotropin-releasing hormone on prolactin release and on prolactin and growth hormone synthesis in pituitary cells in culture. Endocrinology 1976; 98: 1147.PubMedCrossRefGoogle Scholar
  20. 20.
    Dannies PS, Tashjian AH Jr. Action of cholera toxin on hormone synthesis and release in GH cells: evidence that adenosine 3’5’monophosphate does not mediate the decrease in growth hormone synthesis caused by thyrotropin-releasing hormone. Endocrinology 1980; 106: 1532.PubMedCrossRefGoogle Scholar
  21. 21.
    Koch BD, Dorflinger LJ, Schonbrunn A. Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin: evidence for coupling of N to decreases in intracellular free calcium. J Biol Chem 1985; 260 (“24): 13138–45.Google Scholar
  22. 22.
    Miller JP. Cyclic nucleotide analogues. In: Cramer H, Schultz J, eds. Cyclic 3’5’ nucleotides: mechanism of action. New York: John Wiley and Sons, 1977: 77.Google Scholar
  23. 23.
    Koch BD, Schonbrunn A. A transmembrane K+ gradient2+ is required for somatostatin to decrease intracellular free [Ca] and inhibit hormone release via a cAMP-independent mechanism. Proceedings of the 16th Meeting of the Society for Neuroscience, 1986: 734.Google Scholar
  24. 24.
    Koch BD, Schonbrunn A. The somatostatin receptor is directly coupled to adenylate cyclase in GH4C1 pituitary cell membranes. Endocrinology 1984; 114: 1784.PubMedCrossRefGoogle Scholar
  25. 25.
    Gilman AG. G proteins and dual control of adenylate cyclase. Cell 1984; 36: 577.PubMedCrossRefGoogle Scholar
  26. 26.
    De Lean A, Stadel JM, Lefkowitz RJ. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclasecoupled B-adrenergic receptor. J Biol Chem 1980; 255: 7108.PubMedGoogle Scholar
  27. 27.
    Ui M, Katada T, Murayama T, et al. Islet-activating protein, pertussis toxin: a specific uncoupler of receptor-mediated inhibition of adenylate cyclase. In: Greengard P, ed. Advances in cyclic nucleotide and protein phosphorylation research, vol 17. New York: Raven Press, 1984: 145.Google Scholar
  28. 28.
    Hewlett EL, Cronin MJ, Moss J, Anderson H, Myers GH, Pearson RD. Pertussis toxin: lessons from biological and biochemical effects in different cells. In: Greengard P, ed. Advances in cyclic nucleotide and protein phosphorylation research, vol 17. New York: Raven Press, 1984: 173.Google Scholar
  29. 29.
    Sekura RD. Pertussis toxin: a tool for studying the regulation of adenylate cyclase. Methods Enzymol 1985; 109: 588.Google Scholar
  30. 30.
    Wojcikiewicz RJH, Dobson PRM, Irons LQ, Robinson A, Brown BL. The relationship between pertussis-toxin induced ADP-ribosylation of a plasma-membrane protein and reversal of muscarinic inhibition of prolactin secretion in GH3 cells. Biochem J 1984; 224: 339.PubMedGoogle Scholar
  31. 31.
    Yajima, Akita Y, Saito T. Pertussis toxin blocks the inhibitory effects of somatostatin on cAMP-dependent vasoactive intestinal peptide and cAMP-independent thyrotropin releasing hormone-stimulated prolactin secretion in GH3 cells. J Biol Chem 1986; 261: 2684.Google Scholar
  32. 32.
    Neer EJ, Lok JM, Wolf LG. Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase. J Biol Chem 1984; 259: 14, 222.Google Scholar
  33. 33.
    Van Dop C, Yamanaka G, Steinberg F, et al. ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors. J Biol Chem 1984; 259: 23.PubMedGoogle Scholar
  34. 34.
    Gierschik P, Falloon J, Milligan G, Pines M, Gallin JI, Spiegel A. Immunochemical evidence for a novel pertussis toxin substrate in human neutrophils. J Biol Chem 1986; 261: 8058.PubMedGoogle Scholar
  35. 35.
    Florio VA, Sternweis PC. Reconstitution of resolved muscarinic cholinergic receptors with purified GTP-binding proteins. J Biol Chem 1985; 260: 3477.PubMedGoogle Scholar
  36. 36.
    Schlegel W, Wuarit F, Wollheim CB, Zahnd GR. Somatostatin lowers the cytosolic free Ca concentration in clonal rat pituitary cells (GH3 cells). Cell Calcium 1984; 5: 223.PubMedCrossRefGoogle Scholar
  37. 37.
    Rink TJ, Montecucco C, Hesketh TR, Tsien RY. Lymphocyte membrane potential assessed with fluorescent probes. Biochim Biophys Acta 1980; 595: 15.PubMedCrossRefGoogle Scholar
  38. 38.
    Rink TJ. Measurement of membrane potential with chemical probes. Lipid Membr Biochem 1982; B423: 1.Google Scholar
  39. 39.
    Waggoner AS. Dye indicators of membrane potential. Annu Rev Biophys Bioeng 1979; 8: 47.PubMedCrossRefGoogle Scholar
  40. 40.
    Schlegel W, Wuarin F, Zbaren C, Wollheim CB, Zahnd GR. Pertussis toxin selectively abolishes hormone induced lowering of cytosolic calcium in GH cells. FEBS Lett 1985; 189: 27.PubMedCrossRefGoogle Scholar
  41. 41.
    Taraskevich PS, Douglas WW. Electrical behaviour in a line of anterior pituitary cells (GH cells) and the influence of the hypothalamic peptide, thyrotrophin releasing factor. Neuroscience 1980; 5: 421.PubMedCrossRefGoogle Scholar
  42. 42.
    Dubinsky JM, Oxford GS. Ionic currents in two strains of rat anterior pituitary tumor cells. J Gen Physiol 1984; 83: 309.PubMedCrossRefGoogle Scholar
  43. 43.
    Barker JL, Dufy B. Peptide and amino acid electropharmacology of cultured mammalian central neurons and clonal pituitary cells. Regni Pept 1985; 4 (suppl): 14.CrossRefGoogle Scholar
  44. 44.
    Borgeat P, Labrie F, Drouin J, et al. Inhibition of adenosine 3’,5’-,monophosphate accumulation in anterior pituitary gland in vitro by growth-hormone-release-inhibiting hormone. Biochem Biophys Res Commun 1974; 56: 1052.PubMedCrossRefGoogle Scholar
  45. 45.
    Kaneko T, Oka H, Munemura M, Suzuki S, Yasuda H, Oda T. Stimulation of guanosine 3’,5’-cyclic monophosphate accumulation in rat anterior pituitary gland in vitro by synthetic somatostatin. Biochem Biophys Res Commun 1974; 61: 53.PubMedCrossRefGoogle Scholar
  46. 46.
    Schofield JG, Mira-Moser F, Schorderet M, Orci L. Somatostatin inhibition of rat growth hormone release in vitro in the presence of BaCl or 3-isobutyl-1-methylxanthine. FEBS Lett 1974; 46: 171.PubMedCrossRefGoogle Scholar
  47. 47.
    Lippmann W, Sestanj J, Nelson VR, Immer HU. Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogs. Experientia 1976; 32:1034.PubMedCrossRefGoogle Scholar
  48. 48.
    Sheppard MS, Spence JW, Kraicer J. Release of growth hormone from purified somatotrophs: role of adenosine 3’,5’-monophosphate and guanosine 3’,5’-monophosphate. Endocrinology 1979; 105: 261.PubMedCrossRefGoogle Scholar
  49. 49.
    Bilezikjian LM, Vale WW. Stimulation of adenosine 3’,5’-monophosphate production by growth hormone-releasing factor and its inhibition by somatostatin in anterior pituitary cells in vitro. Endocrinology 1983; 113: 1726.PubMedCrossRefGoogle Scholar
  50. 50.
    Michel D, Lefebvre G, Labrie F. Interactions between growth hormone-releasing factor, prostaglandin E2 and somatostatin on cyclic AMP accumulation in rat adenohypophyseal cells in culture. Mol Cell Endocrinol 1983; 33: 255.PubMedCrossRefGoogle Scholar
  51. 51.
    Harwood JP, Grewe C, Aguilera G. Actions of growth hormone releasing factor on somatostatin adenylate cyclase and GH release in rat anterior pituitary. Mol Cell Endocrinol 1984; 37: 277.PubMedCrossRefGoogle Scholar
  52. 52.
    Rouleau D, Barden N. Inhibition of anterior pituitary prostaglandin-stimulated adenylyl cyclase activity by somatostatin. Can J Biochem 1981; 59: 307.PubMedCrossRefGoogle Scholar
  53. 53.
    Cronin MJ, Rogol AD, Myers GA, Hewlett EL. Pertussis toxin blocks the somatostatin-induced inhibition of growth hormone release and adenosine 3’,5’-monophosphate accumulation. Endocrinology 1983; 113: 209.PubMedCrossRefGoogle Scholar
  54. 54.
    Yamashita N, Shibuya N, Ogata E. Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone. Proc Natl Acad Sci USA 1986; 83: 6198.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Agnes Schonbrunn
    • 1
  • Bruce D. Koch
    • 1
  1. 1.Laboratory of ToxicologyHarvard School of Public HealthBostonUSA

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