Mechanisms Governing the Release of Growth Hormone from Acutely Dispersed Purified Somatotrophs

  • M. Suzanne Sheppard
  • Jacob Kraicer
  • John V. Milligan
Part of the Biochemical Endocrinology book series (BIOEND)


The problems inherent in the study of the control of adenohypophyseal hormone secretion in vitro using intact tissue or tissue fragments are fourfold: variability of response, lack of viability of tissue in the gland core, relative lack of sensitivity, and the heterogeneity of cell types within the gland, which precludes interpretation of intracellular metabolic events within a specific cell type. Several investigators have used acutely dispersed or cultured adenohypophyseal cells to examine the effects of hypothalamic regulatory hormones as described in recent reviews (Labrie et al., 1976b; Vale et al., 1976). These preparations overcome the problems of variability, viability, and sensitivity associated with the classic whole or hemipituitary studies. However, the difficulties arising from the heterogeneity of the cell type remain. It is not possible, using presently available preparations, save for the use of autoradiographic techniques, to localize alterations of intracellular metabolite involved in the release of one hormone to a specific adenohypophyseal cell type. In light of much evidence showing a lack of specificity of several of the hypothalamic hypophysiotropic hormones (Labrie et al., 1976a,b; Vale et al., 1976), it has become imperative to study a uniform cell population. Cloned tumor cell lines have been used in an attempt to overcome this problem (Tashjian et al., 1968; Hertelendy and Keay, 1974; Dannies et al., 1976), but there is no assurance that intracellular events are not grossly altered in tumor cells.


Growth Hormone Cyclic Nucleotide Hormone Release Growth Hormone Release Basal Release 
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. Bélanger, A., Labrie, F., Borgeat, P., Savary, M., Cote, J., Drouin, J., Schally, A. V., Coy, D. H., Coy, E. J., Immer, H., Sestanj, K., Nelson, V., and Götz, M., 1974, Inhibition of growth hormone and thyrotropin release by growth hormone-release inhibiting hormone, Mol. Cell. Endocrinol. 1: 329.PubMedCrossRefGoogle Scholar
  2. Berridge, M. J., 1975, The interaction of cyclic nucleotides and calcium in the control of cellular activity, Adv. Cyclic Nucleotide Res. 6: 1.PubMedGoogle Scholar
  3. Bicknell, R. J., and Schofield, J. G., 1976, Mechanism of action of somatostatin: Inhibition of ionophore A23187-induced release of growth hormone from dispersed bovine pituitary cells, FEBS Lett. 68: 23.PubMedCrossRefGoogle Scholar
  4. Birge, C. A., Peake, G. T., Mariz, I. K., and Daughaday, W. H., 1967, Radioimmunoas-sayable growth hormone in the rat pituitary gland: Effects of age, sex and hormonal state, Endocrinology 81: 195.PubMedCrossRefGoogle Scholar
  5. Borgeat, P., Chavancy, G., Dupont, A., Labrie, F., Arimura, A., and Schally, A. V., 1972, Stimulation of adenosine 3′:5′-cyclic monophosphate accumulation in anterior pituitary gland in vitro by synthetic luteinizing hormone-releasing hormone, Proc. Natl. Acad. Sci. U.S.A. 69: 2677.PubMedCrossRefGoogle Scholar
  6. Borgeat, P., Labrie, F., Drouin, J., Bélanger, A., Immer, H., Sestanj, K., Nelson, V., Götz, M., Schally, A. V., Coy, D. H., and Coy, E. J., 1974, Inhibition of adenosine 3′, 5′-monophosphate accumulation in anterior pituitary gland in vitro by growth hormone-release inhibiting hormone, Biochem. Biophys. Res. Commun. 56: 1052.PubMedCrossRefGoogle Scholar
  7. Boss, B., Vale, W., and Grant, G., 1975, Hypothalamic hormones, in: Biochemical Actions of Hormones (G. Litwack, ed.), pp. 87–118, Academic Press, New York.CrossRefGoogle Scholar
  8. Brazeau, P., Vale, W., Burgus, R., Ling, N., Butcher, M., Rivier, J., and Guillemin, R., 1973, Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone, Science 179: 77.PubMedCrossRefGoogle Scholar
  9. Brown, M., and Vale, W., 1975, Growth hormone release in the rat: Effects of somatostatin and thyrotropin-releasing factor, Endocrinology 97: 1151.PubMedCrossRefGoogle Scholar
  10. Burr, R. G., 1969, An automated method for serum calcium utilizing ethylene diamine tetra acetic acid, Clin. Chem. 15: 1191.PubMedGoogle Scholar
  11. Carlson, H. E., Mariz, I. K., and Daughaday, W. H., 1974, Thyrotropin-releasing hormone stimulation and somatostatin inhibition of growth hormone secretion from perfused rat adenohypophyses, Endocrinology 94: 1709.PubMedCrossRefGoogle Scholar
  12. Cooper, R. H., McPherson, M., and Schofield, J. G., 1972, The effect of prostaglandins on ox pituitary content of adenosine 3′:5′-cyclic monophosphate and the release of growth hormone, Biochem. J. 127: 143.PubMedGoogle Scholar
  13. Dannies, P. S., Gautvik, K. M., and Tashjian, A. H.,Jr., 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.PubMedCrossRefGoogle Scholar
  14. Douglas, W. W., 1968, Stimulus-secretion coupling: The concept and clues from chromaffin and other cells, Br. J. Pharmacol. 34: 451.PubMedCrossRefGoogle Scholar
  15. Duncan, D. B., 1955, Multiple range and multiple F tests, Biometrics 11: 1.CrossRefGoogle Scholar
  16. Eto, S., Wood, J. M., Hutchins, M., and Fleischer, N., 1974, Pituitary 45Ca++ uptake and release of ACTH, GH, and TSH: Effect of verapamil, Am. J. Physiol. 226: 1315.PubMedGoogle Scholar
  17. Hedge, G. A., 1977, Roles for the prostaglandins in the regulation of anterior pituitary secretion, Life Sci. 20: 17.PubMedCrossRefGoogle Scholar
  18. Hertelendy, F., 1971, Studies on growth hormone secretion. II. Stimulation by prostaglandins in vitro, Acta Endocrinol. (Copenhagen) 68: 355.Google Scholar
  19. Hertelendy, F., and Keay, L., 1974, Studies on growth hormone secretion. VI. Effects of dibutyryl cyclic AMP, prostaglandin E1, and indomethacin on growth and hormone secretion by rat pituitary tumor cells in culture, Prostaglandins 6: 217.PubMedGoogle Scholar
  20. Hymer, W. C., Kraicer, J., Bencosme, S. A., and Haskill, J. S., 1972, Separation of somatotrophs from the rat adenohypophysis by velocity and density gradient centrif-ugation. Proc. Soc. Exp. Biol. Med. 141: 966.PubMedGoogle Scholar
  21. Hymer, W. C., Evans, W. H., Kraicer, J., Mastro, A., Davis, J., and Griswold, E., 1973, Enrichment of cell types from the rat adenohypophysis by sedimentation at unit gravity, Endocrinology 92: 275.PubMedCrossRefGoogle Scholar
  22. Kaneko, T., Oka, H., Munemura, M., Suzuki, S., Yasuda, H., and Oda, T., 1974, Stimulation of guanosine 3′,5′-cyclic monophosphate accumulation in rat anterior pituitary gland in vitro by synthetic somatostatin, Biochem. Biophys. Res. Commun. 61: 53.PubMedCrossRefGoogle Scholar
  23. Kraicer, J., 1975, Mechanisms involved in the release of adenohypophysial hormones, in: The Anterior Pituitary (A. Tixier-Vidal and M. G. Farquhar, eds.), pp. 21–43, Academic Press, New York.Google Scholar
  24. Kraicer, J., and Hymer, W. C., 1974, Purified somatotrophs from rat adenohypophysis: Response to secretagogues, Endocrinology 94: 1525.PubMedCrossRefGoogle Scholar
  25. LaBella, F. S., and Vivian, S. R., 1971, Effect of synthetic TRF on hormone release from bovine anterior pituitary in vitro, Endocrinology 88: 787.PubMedCrossRefGoogle Scholar
  26. Labrie, F., De Lean, A., Barden, N., Ferland, L., Drouin, J., Borgeat, P., Beaulieu, M., and Morin, O., 1976a, New aspects of the mechanism of action of hypothalamic regulatory hormones, in: Current Topics in Molecular Endocrinology (F. Labrie, J. Meites, and G. Pelletier, eds.), Vol. 3, Hypothalamus and Endocrine Functions, pp. 147–169, Springer Science+Business Media New York .Google Scholar
  27. Labrie, F., Pelletier, G., Borgeat, P., Drouin, J., Ferland, L., and Bélanger, A., 1976b, Mode of action of hypothalamic regulatory hormones in the adenohypophysis, in: Frontiers in Neuroendocrinology (L. Martini and W. F. Ganong, eds.), Vol. 4, pp. 63–93, Raven Press, New York.Google Scholar
  28. Lemay, A., and Labrie, F., 1972, Calcium-dependent stimulation of prolactin release in rat anterior pituitary in vitro by N6-monobutyryl adenosine 3′,5′-monophosphate, FEBS Lett. 20: 7.PubMedCrossRefGoogle Scholar
  29. Lippmann, W., Sestanj, K., Nelson, V. R., and Immer, H. U., 1976, Antagonism of prostaglandin-induced cyclic AMP accumulation in the rat anterior pituitary in vitro by somatostatin analogues, Experientia 32: 1034.PubMedCrossRefGoogle Scholar
  30. Lockhart Ewart, R. B., and Taylor, K. W., 1971, The regulation of growth hormone secretion from the isolated rat anterior pituitary in vitro: The role of adenosine 3′:5′-cyclic monophosphate, Biochem. J. 124: 815.Google Scholar
  31. Machlin, L. J., Jacobs, L. S., Cirulis, N., Kimes, R., and Miller, R., 1974, An assay for growth hormone and prolactin-releasing activities using a bovine pituitary cell culture system, Endocrinology 95: 1350.PubMedCrossRefGoogle Scholar
  32. McCann, S. M., Ojeda, S. R., Harms, P. G., Wheaton, J. E., Sundberg, D. K., and Fawcett, C. P., 1976, Role of prostaglandins (PGs) in the control of adenohypophyseal hormone secretion, in: Current Topics in Molecular Endocrinology (F. Labrie, J. Meites, and G. Pelletier, eds.), Vol. 3, Hypothalamus and Endocrine Functions, pp. 21–35, Springer Science+Business Media New York .Google Scholar
  33. Milligan, J. V., and Kraicer, J., 1971, 45Ca uptake during the in vitro release of hormones from the rat adenohypophysis, Endocrinology 89: 766.PubMedCrossRefGoogle Scholar
  34. Milligan, J. V., and Kraicer, J., 1974, Physical characteristics of the Ca++ compartments associated with in vitro ACTH release, Endocrinology 94: 435.PubMedCrossRefGoogle Scholar
  35. Milligan, J. V., Kraicer, J., Fawcett, C. P., and Illner, P., 1972, Purified growth hormone releasing factor increases 45Ca uptake into pituitary cells, Can. J. Physiol. Pharmacol. 50: 613.PubMedCrossRefGoogle Scholar
  36. Moriarty, C. M., 1977, Involvement of intracellular calcium in hormone secretion from rat pituitary cells, Mol. Cell. Endocrinol. 6: 349.PubMedCrossRefGoogle Scholar
  37. Moriarty, C. M., 1978, Role of calcium in the regulation of adenohypophysial hormone release, Life Sci. 23: 185.PubMedCrossRefGoogle Scholar
  38. Peake, G. T., 1973, The role of cyclic nucleotides in the secretion of pituitary growth hormone, in: Frontiers in Neuroendocrinology (W. F. Ganong and L. Martini, eds.), Vol. 3, pp. 173–208, Oxford University Press, New York.Google Scholar
  39. Peake, G. T., Steiner, A. L., and Daughaday, W. H., 1972, Guanosine 3′5′ cyclic monophosphate is a potent pituitary growth hormone secretagogue, Endocrinology 90: 212.PubMedCrossRefGoogle Scholar
  40. Rasmussen, H., and Goodman, D. B. P., 1977, Relationships between calcium and cyclic nucleotides in cell activation, Physiol. Rev. 57: 421.PubMedGoogle Scholar
  41. Schally, A. V., Arimura, A., Kastin, A. J., Uehara, T., Coy, D. H., Coy, E. J., and Takahara, J., 1973, Inhibition of the release of growth hormone in vitro by α melanocyte stimulating hormone, Biochem. Biophys. Res. Commun. 52: 1314.PubMedCrossRefGoogle Scholar
  42. Schofield, J. G., and McPherson, M., 1974, Increase in pituitary adenosine 3′:5′-cyclic monophosphate content and potentiation of growth hormone release from heifer anterior pituitary slices incubated in the presence of 3-isobutyl-l-methylxanthine, Biochem. J. 142: 295.PubMedGoogle Scholar
  43. Schofield, J. G., Mira-Moser, F., Schorderet, M., and Orci, L., 1974, Somatostatin inhibition of rat growth hormone release in vitro in the presence of BaCl2 or 3-isobutyl-1-methylxanthine, FEBS Lett. 46: 171.PubMedCrossRefGoogle Scholar
  44. Shortman, K., 1968, The separation of different cell classes from lymphoid organs. II. The purification and analysis of lymphocyte populations by equilibrium density gradient centrifugation, Aust. J. Exp. Biol. Med. Sci. 46: 375.PubMedCrossRefGoogle Scholar
  45. Snyder, G., and Hymer, W. C., 1975, A short method for the isolation of somatotrophs from the rat pituitary gland, Endocrinology 96: 792.PubMedCrossRefGoogle Scholar
  46. Stachura, M. E., 1976, Influence of synthetic somatostatin upon growth hormone release from perifused rat pituitaries, Endocrinology 99: 678.PubMedCrossRefGoogle Scholar
  47. Steiner, A. L., Peake, G. T., Utiger, R. D., Karl, I. E., and Kipnis, D. M., 1970, Hypothalamic stimulation of growth hormone and thyrotropin release in vitro and pituitary 3′5′-adenosine cyclic monophosphate, Endocrinology 86: 1354.PubMedCrossRefGoogle Scholar
  48. Strauch, G., Girault, D., Rifai, M., and Bricaire, H., 1973, Alpha-MSH stimulation of growth hormone release, J. Clin. Endocrinol. Metab. 37: 990.PubMedCrossRefGoogle Scholar
  49. Sundberg, D. K., Fawcett, C. P., and McCann, S. M., 1976, The involvement of cyclic-3′,5′-AMP in the release of hormones from the anterior pituitary in vitro, Proc. Soc. Exp. Biol. Med. 151: 149.PubMedGoogle Scholar
  50. Takahara, J., Arimura, A., and Schally, A. V., 1974, Effect of catecholamines on the TRH-stimulated release of prolactin and growth hormone from sheep pituitaries in vitro, Endocrinology 95: 1490.PubMedCrossRefGoogle Scholar
  51. Tashjian, A. H.,Jr., Yasumura, Y., Levine, L., Sato, G. H., and Parker, M. L., 1968, Establishment of clonal strains of rat pituitary tumor cells that secrete growth hormone, Endocrinology 82: 342.PubMedCrossRefGoogle Scholar
  52. Trifaro, J. M., 1977, Common mechanisms of hormone secretion, Annu. Rev. Pharmacol. Toxicol. 17: 27.PubMedCrossRefGoogle Scholar
  53. Vale, W. Brazeau, P., Grant, G., Nussey, A., Burgus, R., Rivier, J., Ling, N., and Guillemin, R., 1972, Premières observations sur le mode d’action de la somatostatine, un facteur hypothalamique qui inhibe la sécrétion de l’hormone de croissance, C. R. Acad. Sci. Ser. D. 275: 2913.Google Scholar
  54. Vale, W., Brazeau, P., Rivier, C., Brown, M., Boss, B., Rivier, J., Burgus, R., Ling, N., and Guillemin, R., 1975, Somatostatin, Recent Prog. Horm. Res. 31: 365.PubMedGoogle Scholar
  55. Vale, W., Rivier, C., Brown, M., Chan, L., Ling, N., and Rivier, J., 1976, Applications of adenohypophyseal cell cultures to neuroendocrine studies, in: Current Topics in Molecular Endocrinology (F. Labrie, J. Meites, and G. Pelletier, eds.), Vol. 3, Hypothalamus and Endocrine Functions, pp. 397–429, Springer Science+Business Media New York .Google Scholar
  56. Wilber, J. F., Nagel, T., and White, W. F., 1971, Hypothalamic growth hormone-releasing activity (GRA): Characterization by the in vitro rat pituitary and radioimmunoassay, Endocrinology 89: 1419.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • M. Suzanne Sheppard
    • 1
  • Jacob Kraicer
    • 1
  • John V. Milligan
    • 1
  1. 1.Department of PhysiologyQueen’s UniversityKingstonCanada

Personalised recommendations