Cellular Physiology of Growth Hormone Releasing Hormone

  • Lawrence A. Frohman
Part of the Serono Symposia USA Norwell, Massachusetts book series (SERONOSYMP)


This chapter reviews the mechanisms involved in the normal transduction of the signal generated by binding of growth hormone (GH) releasing hormone (GHRH) to its receptor on the somatotropes in relation to GH secretion, GH synthesis, and cellular proliferation. This chapter also discusses the consequences of altered signal transduction, citing models of both genetic and transgenic origin with both decreased and increased activity of the system.


Growth Hormone Adenylyl Cyclase Cholera Toxin Pituitary Cell Altered Signal Transduction 
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  1. 1.
    Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol 1992;6:1734–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Frohman LA, Downs TR, Chomczynski P. Regulation of growth hormone secretion. Front Neuroendocrinol 1992;13:344–405.PubMedGoogle Scholar
  3. 3.
    Chen C, Vincent JD, Clarke I J. Ion channels and the signal transduction pathways in the regulation of growth hormeone secretion. TEM 1994;5:227–33.PubMedGoogle Scholar
  4. 4.
    Chomczynski P, Brar A, Frohman LA. Growth hormone synthesis and secretion by a somatomammotroph cell line derived from normal adult pituitary of the rat. Endocrinology 1988;123:2275–83.CrossRefGoogle Scholar
  5. 5.
    Gick GG, Zeytin FN, Ling NC, Esch FS, Bancroft C, Brazeau P. Growth hormone-releasing factor regulates growth hormone mRNA in primary cultures of rat pituitary cells. Proc Natl Acad Sci USA 1984;81:1553–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Barinaga M, Yamamoto G, Rivier C, Vale W, Evans R, Rosenfeld MG. Transcriptional regulation of growth hormone gene expression by growth hormone- releasing factor. Nature 1983;306:84–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Barinaga M, Bilezikjian LM, Vale WW, Rosenfeld MG, Evans RM. Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature 1985;314:279–81.PubMedCrossRefGoogle Scholar
  8. 8.
    Billestrup N, Swanson LW, Vale W. Growth hormone-releasing factor stimulates proliferation of somatotroph in vitro. Proc Natl Acad Sci USA 1986;83:6854–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Billestrup N, Mitchell RL, Vale W, Verma IM. Growth hormone-releasing factor induces c-fos expression in cultured primary pituitary cells. Mol Endocrinol 1987;1:300–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Jansson J, Downs TR, Beamer WG, Frohman LA. Receptor-associated resistance to growth hormone-releasing factor in dwarf “little” mice. Science 1986;232:511–2.PubMedCrossRefGoogle Scholar
  11. 11.
    Lin SC, Lin CR, Gukovsky I, Lusis AJ, Sawchenko PE, Rosenfeld MG. Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 1993;364:208–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Godfrey P, Rahal JO, Beamer WG, Copeland NG, Jenkins NA, Mayo KE. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet 1993;4:227–32.PubMedCrossRefGoogle Scholar
  13. 13.
    Jansson J, Downs TR, Beamer WG, Frohman LA. The dwarf “little” (lit/lit) mouse is resistant to growth hormone (GH)-releasing peptide (GH-RP-6) as well as to GH-releasing hormone (GRH). Program 68th Annual Meeting of the Endocrine Society, 1986;#397(abstr).Google Scholar
  14. 14.
    Charlton HM, Clark RG, Robinson IC, Porter-Goff AEP, Cox BS, Bugnon C, et al. Growth hormone-deficient dwarfism in the rat: a new mutation. J Endocrinol 1988;119:51–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Downs TR, Frohman LA. Evidence for a defect in growth hormone-releasing factor signal transduction in the dwarf (dw/dw) rat pituitary. Endocrinology 1991;129:58–67.PubMedCrossRefGoogle Scholar
  16. 16.
    Zeitler PA, Downs TR, Frohman LA. (Gs-alpha MS). Impaired growth hormone releasing-hormone signal transduction in the dwarf (dw) rate is independent of a generalized defect in the stimulatory G-protein, Gs-alpha. Endocrinology 1993;133:2782–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Zeitler PA, Downs TR, Frohman LA. Development of pituitary cell types in the spontaneous dwarf (dw) rat: evidence for an isolated defect in somatotroph differentiation. Endocrine 1994;2:729–33.Google Scholar
  18. 18.
    Pinhas-Hamiel O, Zeitler P. Impaired response to GHRP-6 in somatotrophs from dwarf (dw) rats. Program 76th Annual Meeting of the Endocrinc Society 1994;#663(abstr).Google Scholar
  19. 19.
    Lloyd RV, Jin L, Chang A, Kulig E, Camper SA, Ross BD, et al. Morphological effects of hGRH gene expression on the pituitary, liver, and pancreas of MT- hGRH transgenic mice. An in situ hybridization analysis. Am J Pathol 1992;141:895–906.PubMedGoogle Scholar
  20. 20.
    Burton FH, Hasel KW, Bloom FE, Sutcliffe JG. Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene. Nature 1991;350:74–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Frohman LA, Thominet JL, Szabo M. Ectopic growth hormone releasing factor syndromes. In: Raiti S, Tolman R, eds. Human growth hormone. New York: Plenum, 1986:347–60.Google Scholar
  22. 22.
    Caplan R, Koob L, Abellera RM, Pagliara AS, Kovacs K, Randall R. Cure of acromegaly by operative removal of an islet cell tumor of the pancreas. Am J Med 1978;64:874–82.PubMedCrossRefGoogle Scholar
  23. 23.
    Ezzat S, Asa SL, Stefaneanu L, Whittom R, Smyth HS, Horvath E, et al. Somatotroph hyperplasia without pituitary adenoma associated with a longstanding GHRH-producing bronchial carcinoid tumor. J Clin Endocrinol Metab 1994;78:555–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Landis CA, Harsh G, Lyons J, Davis RL, McCormick F, Bourne HR. Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein. J Clin Endocrinol Metab 1990;71:1416–20.PubMedCrossRefGoogle Scholar
  25. 25.
    Spada A, Arosio M, Bochicchio D, Bazzoni N, Vallar L, Bassetti M, et al. Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 1990;71:1421–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991;325:1688–95.PubMedCrossRefGoogle Scholar

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© Springer-Verlag New York, Inc. 1996

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  • Lawrence A. Frohman

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