Multiple Transduction Mechanisms Activated by the Neuropeptide Somatostatin

  • Agnes Schonbrunn
Part of the Wenner-Gren Center International Symposium Series book series (WGCISS)


Because somatostatin inhibits secretion in a wide variety of target cells, studies probing its mechanism of action have focused on the role played by two of the intracellular messengers known to regulate secretory processes: cyclic AMP and calcium (see reviews 1–5). Thus, somatostatin has been proposed to both regulate the concentrations of these intracellular messengers and also to modify their effectiveness. Although direct evidence showing that somatostatin is able to regulate the potency of either cyclic AMP or calcium is still lacking, recent studies have begun to clarify how somatostatin alters the concentrations of these two intracellular mediators and the extent to which such changes are involved in eliciting somatostatin’s effects on secretion. This review summarizes studies on the mechanisms by which somatostatin inhibits growth hormone (GH) and prolactin (PRL) secretion from the GH4C1 pituitary cell line. These cells have two major advantages for elucidating the biochemical mediators involved in somatostatin action. First, the effects of somatostatin to inhibit GH and PRL secretion in GH4C1 cells parallel its actions in estrogen primed pituitary cells both in primary culture and in vivo (4,6–9). Second, GH4C1 cells are clonal in origin and therefore both hormonal and biochemical responses are produced by the same population of target cells and can be quantitatively correlated.


Vasoactive Intestinal Peptide Hormone Secretion Pituitary Cell Thyrotropin Release Hormone Pertussis Toxin 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Reichlin, S. (1983). Somatostatin. New Eng. J. Med., 309, 1495–1501 and 1556–1563.Google Scholar
  2. 2.
    Gottesman, I.S., Mandarino, L.J., and Gerich, J.E. (1982). Somatostatin: Its Role in Health and Disease. In Special Topics in Endocrinology and Metabolism. (eds. M. P. Cohen and P. P. Foa ). Alan R. Liss, New York, 4, 177–243.Google Scholar
  3. 3.
    Pace, C.S. (1980). Somatostatin: ControT of Stimulus-Secretion Coupling in Pancreatic Islet Cells. In Peptides: Integrators of Cell and Tissue Function. (ed. F. E. Bloom ). Raven Press, New York, 163–195.Google Scholar
  4. 4.
    Schonbrunn, A., Dorflinger, L.J. and Koch, B.D. (1985). Mechanisms of Somatostatin Action in Pituitary Cells. In Advances in Experimental Medicine and Biology. (eds. Y. Patel and G. Tannenbaum ). Plenum Press, New York, 118, 305–324.Google Scholar
  5. 5.
    Patel, Y.C. and Srikant, C.B. (1986). Somatostatin Mediation of Adenohypophysial Secretion. Ann. Rev. Physiol., 48, 551–567.CrossRefGoogle Scholar
  6. 6.
    Vale, W., Rivier, C., Brazeau, P. and Guillemin, R. (1974). Effects of Somatostatin on the Secretion of Thyrotropin and Prolactin. Endocrinology, 95, 968–977.CrossRefGoogle Scholar
  7. 7.
    Drouin, J., De Lean, A., RaiTiville, D., Lachance, R. and Labrie, F. (1976). Characteristics of the Interaction between Thyrotropin-Releasing Hormone and Somatostatin for Thyrotropin and Prolactin Release. Endocrinology, 98, 514–521.CrossRefGoogle Scholar
  8. 8.
    Enjalbert, A., Epelbaum, J., Arancibia, S., Tapia-Arancibia, L., Blute-Pajot, M.-T., and Kordon, C. (1982). Reciprocal Interactions of Somatostatin with Thyrotropin-Releasing Hormone and Vasoactive Intestinal Peptide on Prolactin and Growth Hormone Secretion In Vitro. Endocrinology, 111, 42–47.CrossRefGoogle Scholar
  9. 9.
    Cooper, G.R. and Shin, S.H. (1981). Somatostatin Inhibits Prolactin Secretion in the Estradiol Primed Male Rat. Can. J. Physiol., 59, 1082–1088.CrossRefGoogle Scholar
  10. 10.
    Schonbrunn, A. and Tashjian Jr., A.H. (1978). Characterization of Functional Receptors for Somatostatin in Rat Pituitary Cells in Culture. J. Biol. Chem., 253, 6473–6483.Google Scholar
  11. 11.
    Dorflinger, L.J. and Schonbrunn, A. (1983). Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells. Endocrinology, 113, 1551–1558.CrossRefGoogle Scholar
  12. 12.
    Westendorf, J.M. and Sc onbrunn, A. (1982). Bombesin Stimulates Prolactin and Growth Hormone Release by Pituitary Cells in Culture. Endocrinology, 110, 352–358.CrossRefGoogle Scholar
  13. 13.
    Dorflinger, L.J. and Schonbrunn, A (1983). Somatostatin Inhibits Vasoactive Intestinal Peptide-Stimulated Cyclic Adenosine Monophosphate Accumulation in GH Pituitary Cells. Endocrinology, 113, 1541–1550.CrossRefGoogle Scholar
  14. 14.
    Gershengorn, M.C. (1986). Mechanism of Thyrotropin Releasing Hormone Stimulation of Pituitary Hormone Secretion. Ann. Rev. Physiol., 48, 515–526.CrossRefGoogle Scholar
  15. 15.
    Williams, J.A. (1984). Regulatory Mechanisms in Pancreas and Salivary Acini. Ann. Rev. Physiol., 46, 361–375.CrossRefGoogle Scholar
  16. 16.
    Sutton, C.A. and Martin, T.F.J. (1982) Thyrotropin Releasing Hormone (TRH) Selectively and Rapidly Stimulates Phosphatidylinositol Turnover in GH Pituitary Cells: A Possible Second Step of TRH Action. Endocrinology, 110, 1273–1280.CrossRefGoogle Scholar
  17. 17.
    Schonbrunn, A., Rorstad, O.P., Westendorf, J.M., and Martin, J.B. (1983). Somatostatin Analogs: Correlation Between Receptor Binding Affinity and Biological Potency in GH Pituitary Cells. Endocrinology, 113, 1559–1567.CrossRefGoogle Scholar
  18. 18.
    Presky, D.H. and Schonbrunn, A. (1986). Receptor-Bound Somatostatin and Epidermal Growth Factor are Processed Differently in GH4C1 Rat Pituitary Cells. J. Cell Biol., 102, 878–888.CrossRefGoogle Scholar
  19. 19.
    U nies, P.S., Gautvik, K.M. and Tashjian Jr., A.H. (1976). 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, 98, 1147–1159.CrossRefGoogle Scholar
  20. 20.
    Dannies, P.S., and Tashjian Jr., A.H. (1980). 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, 106, 1532–1536.CrossRefGoogle Scholar
  21. 21.
    Koch, B.D., Dorflinger, L.J. and Schonbrunn, A. (1985). Pertussis Toxin Blocks Both Cyclic AMP-Mediated and Cyclic AMP-Independent Actions of Somatostatin: Evidence for Coupling of Ni to Decreases in Intracellular Free Calcium. J. Biol. Chem., 260, 13138–13145.Google Scholar
  22. 22.
    Koch, B.D. and Efiribrunn, A. (1986). A Transmembrane K+ Gradient is Required for Somatostatin to Decrease Intracellular Free [Ca2] and Inhibit Hormone Release via a cAMP-Independent Mechanism. Proc. of the 16th Meeting of the Society for Neuroscience, p.734.Google Scholar
  23. 23.
    Koch, B.D. and Schonbrunn, A. Characterization of the Cyclic AMP- Independent Actions of Somatostatin: A Transmembrane Potassium Gradient is Required for Somatostatin Inhibition of Hormone Secretion. Submitted.Google Scholar
  24. 24.
    Koch, B.D. and Schonbrunn, A. (1984). The Somatostatin Receptor is Directly Coupled to Adenylate Cyclase in GH4C1 Pituitary Cell Membranes. Endocrinology, 114, 1784–1790.CrossRefGoogle Scholar
  25. 25.
    Gilman, A.G. (1984). G Proteins and Dual Control of Adenylate Cyclase. Cell, 36, 577–579.CrossRefGoogle Scholar
  26. 26.
    De Lean, A., Stadel, J.M. and Lefkowitz, R.J. (1980). A Ternary Complex Model Explains the Agonist-Specific Binding Properties of the Adenylate Cyclase-Coupled B-adrenergic Receptor. J. Biol. Chem., 255, 7108–7117.Google Scholar
  27. 27.
    Ui, M., Katada, T., Murayama, T., Kurose, H., Yajima, M., Tamura, M., Nakamura, T. and Nogimori, K. (1984). Islet-Activating Protein, Pertussis Toxin: A Specific Uncoupler of Receptor-Mediated Inhibition of Adenylate Cyclase. In Advances in Cyclic Nucleotide and Protein Phosphorylation Research. (ed. P. Greengard ). Raven Press, New York, 17, 145–151.Google Scholar
  28. 28.
    Hewlett, E.L., Cronin, M.J., Moss, J., Anderson, H., Myers, G.H. and Pearson, R.D. (1984). Pertussis Toxin: Lessons from Biological and Biochemical Effects in Different Cells. In Advances in Cyclic Nucleotide and Protein Phosphorylation Research. (ed. P. Greengard ). Raven Press, New York, 17, 173–182.Google Scholar
  29. 29.
    Sekura, R.D. (1985). Pertussis Toxin: A Tool for Studying the Regulation of Adenylate Cyclase. Methods in Enzymology, 109, 558–566.CrossRefGoogle Scholar
  30. 30.
    ló cikiewicz, R.J.H., Dobson, P.R.M., Irons, L.Q., Robinson, A. and Brown, B.L. (1984). 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., 224, 339–342.Google Scholar
  31. 31.
    Yajima, Y., Akita, Y. and Saito, T. (1776). Pertussis Toxin Blocks the Inhibitory Effects of Somatostatin on cAMPDependent Vasoactive Intestinal Peptide and cAMP-Independent Thyrotropin Releasing Hormone-Stimulated Prolactin Secretion in GH3 Cells. J. Biol. Chem., 261, 2684–2689.Google Scholar
  32. 32.
    Neer, E.J., Lok, J.M. and Wolf, L.G. (1984). Purification and Properties of the Inhibitory Guanine Nucleotide Regulatory Unit of Brain Adenylate Cyclase. J. Biol. Chem., 259, 14222–14229.Google Scholar
  33. 33.
    Van Dop, C., Yamanaka, G., Steinberg, F., Sekura, R.D., Manclark, C.R., Stryer, L. and Bourne, H.R. (1984). ADP-Ribosylation of Transducin by Pertussis Toxin Blocks the Light-Stimulated Hydrolysis of GTP and cGMP in Retinal Photoreceptors. J. Biol. Chem., 259, 23–26.Google Scholar
  34. 34.
    Gierschik, P., Falloon, J., Millian, G., Pines, M., Gallin, J.I. and Spiegel, A. (1986). Immunochemical Evidence for a Novel Pertussis Toxin Substrate in Human Neutrophils. J. Biol. Chem., 261, 8058–8062.Google Scholar
  35. 35.
    Florio, V.A. Sternweis, P.C. (1985). Reconstitution of Resolved Muscarinic Cholinergic Receptors with Purified GTP-Binding Proteins. J. Biol. Chem., 260, 3477–3483.Google Scholar
  36. 36.
    Schlegel, W., Wuarin, F., Wollheim, C. B. and Zahnd, G.R. (1984). Somatostatin Lowers the Cytosolic Free Ca2+ Concentration in Clonal Rat Pituitary Cells (GH3 Cells). Cell Calcium, 5, 223–236.CrossRefGoogle Scholar
  37. 37.
    Koch, B.D. and Schonbrunn, A. Characterization of the Cyclic AMP-Independent Actions of Somatostatin. A Transmembrane Potassium Ion Gradient is Required for Somatostatin to Cause Hyperpolarization and Decrease Intracellular Free Calcium. Submitted.Google Scholar
  38. 38.
    Schlegel, W., Wuarin, F., Zbaren, C., Wollheim, C.B. and Zahnd, G.R. (1985). Pertussis Toxin Selectively Abolishes Hormone Induced Lowering of Cytosolic Calcium in GH3 Cells. FEBS Lett., 189, 27–32.CrossRefGoogle Scholar
  39. 39.
    Taraskevich, P.S. Douglas, W.W. (1980). Electrical Behaviour in a Line of Anterior Pituitary Cells (GH Cells) and the Influence of the Hypothalamic Peptide, Thyrotrophin Releasing Factor. Neuroscience, 5, 421–431.CrossRefGoogle Scholar
  40. 40.
    Dubinsky, J.M. and Oxford, G.S. (1984). Ionic Currents in Two Strains of Rat Anterior Pituitary Tumor Cells. J. Gen. Physiol., 83, 309–339.CrossRefGoogle Scholar
  41. 41.
    Barker, J. and Dufy, B. (1985). Peptide and Amino Acid Electropharmacology of Cultured Mammalian Central Neurons and Clonal Pituitary Cells. Regul. Peptides Suppl., 4, 14–22.CrossRefGoogle Scholar

Copyright information

© The Wenner-Gren Center 1987

Authors and Affiliations

  • Agnes Schonbrunn

There are no affiliations available

Personalised recommendations