Immunomodulation by Growth Hormone in Humans

  • Robert Rapaport
Part of the Hans Selye Symposia on Neuroendocrinology and Stress book series (HSSN, volume 3)


The role of growth hormone in the establishment and maintenance of the immune system of animals has been well documented. Beginning with the demonstration of involution of the thymus gland following hypophysectomy,1 many studies have shown diminished immune functions in hypophysectomized animals that were reversible by growth hormone administration.2–8 Growth hormone has also been reported to stimulate DNA synthesis and c-myc proto-oncogene expression9 as well as superoxide anion production10,11 in hypophysectomized rats.


Growth Hormone Growth Hormone Deficiency Human Growth Hormone Growth Hormone Receptor Growth Hormone Treatment 
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.
    P.E. Smith, Effect of hypohysectomy upon the involution of the thymus in the rat, Anat. Rec. 47:119 (193).Google Scholar
  2. 2.
    P.M. Lundin, Action of hypophysectomy on antibody formation in the rat, Acta. Pathol. Microbiol. Scand. 48:351 (1960).PubMedCrossRefGoogle Scholar
  3. 3.
    L. Enerback, P.M. Lundin and J. Mellgren, Pituitary hormones elaborated during stress. Action on lymphoid tissues, serum proteins and antibody titres, Acta. Pathol. Microbiol. Scand. (Suppl.) 144:141 (1961).Google Scholar
  4. 4.
    R.H. Gisler and L. Schenkel-Hulliger, Hormonal regulation of the immune response II. Influence of pituitary and adrenal activity on immune responsiveness in vitro, Cell. Immunol. 2:646 (1971).PubMedCrossRefGoogle Scholar
  5. 5.
    J. Comsa, J.A. Schwarz and H. Neu, Interaction between thymic hormone and hypophyseal growth hormone on production of precipitating antibodies in the rat, Immunol. Commun. 3:11 (1974).PubMedGoogle Scholar
  6. 6.
    E. Nagy and I. Berczi, Immunodeficiency in hypophysectomized rats, Acta Endocrinol. 89:530 (1978).PubMedGoogle Scholar
  7. 7.
    E. Nagy, I. Berczi and H.G. Friesen, Regulation of immunity in rats by lactogenic and growth hormones, Acta Endocrinol. 102:351 (1983).PubMedGoogle Scholar
  8. 8.
    I. Berczi, “Pituitary Function and Immunity,” CRC Press, Boca Raton, FL (1986).Google Scholar
  9. 9.
    I. Berczi, E. Nagy, S.M. DeToledo, R.J. Matusik and H.G. Friesen, Pituitary hormones regulate c-myc and DNA synthesis in lymphoid tissue, J. Immunol. 146:2201 (1991).PubMedGoogle Scholar
  10. 10.
    C.K. Edwards, III, L.M. Yunger, R.M. Lorence, R. Dantzer and K.W. Kelley, The pituitary gland is required for protection against lethal effects of Salmonella tvphimurium. Proc. Natl. Acad. Sci. (USA) 88:2274 (1991).PubMedCrossRefGoogle Scholar
  11. 11.
    C.K. Edwards, III, S.M. Ghiasuddin, L.B. Yunger, R.M. Lorence, S. Arkins, R. Dantzer and K.W. Kelley, In Vivo administration of recombinant growth hormone or gamma interferon activates macrophages: Enhanced resistance to experimental Salmonella tvphimurium infection is correlated with generation of reactive oxygen intermediates, Infect. Immun. 60:2514 (1992).PubMedGoogle Scholar
  12. 12.
    W. Pierpaoli and E. Sorkin, Relationship between thymus and hypophysis, Nature 215:834 (1967).CrossRefGoogle Scholar
  13. 13.
    W. Pierpaoli and E. Sorkin, Hormones and immunologic capacity I. Effect of heterologous anti-growth hormone(ASTH)antiserum on thymus and peripheral lymphatic tissue in mice. Induction of a wasting syndrome, J. Immunol. 101:1036 (1968).PubMedGoogle Scholar
  14. 14.
    C. Baroni, Thymus, peripheral lymphoid tissues and immunological responses of the pituitarydwarf mouse, Experientia 23:282 (1967).PubMedCrossRefGoogle Scholar
  15. 15.
    C.D. Baroni, N. Fabris and G. Bertoli, Effects of hormones on development and function of lymphoid tissues. Synergistic action of thyroxin and somatotropic hormone in pituitary dwarf mice, Immunology 17:303 (1969).PubMedGoogle Scholar
  16. 16.
    C.D. Baroni, P.C. Pesando and G. Bertoli, Effects of hormones on development of lymphoid tissues. II. Delayed development of immunological capacity in pituitary dwarf mice, Immunology 21:455 (1971).PubMedGoogle Scholar
  17. 17.
    F. Dumont, F. Roert and P. Bischoff, T and B lymphocytes in pituitary dwarf Snell-Bagg mice, Immunology 38:23 (1979).PubMedGoogle Scholar
  18. 18.
    N. Fabris, W. Pierpaoli and E. Sorkin, Hormones and the immunological capacity. III. The immunodeficiency disease of the hypopituitary Snell-Bagg dwarf mouse, Clin. Exp. Immunol. 9:209 (1971).PubMedGoogle Scholar
  19. 19.
    N. Fabris, W. Pierpaoli and E. Sorkin, Hormones and the immunological capacity. IV. Restorative effects of developmental hormones or of lymphocytes on the immunodeficiency syndrome of the dwarf mouse, Clin. Exp. Immunol. 9:227 (1971).PubMedGoogle Scholar
  20. 20.
    R.J. Duquesnoy, P.K. Kalpaktsoglou and R.A. Good, Immunological studies on the Snell-Bagg pituitary dwarf mouse, Proc. Soc. Exp. Biol. Med. 133:201 (1970).PubMedGoogle Scholar
  21. 21.
    R.J. Duquesnoy, Immunodeficiency of the thymus-dependent system of the Ames dwarf mouse, J. Immunol. 108:1578 (1972).PubMedGoogle Scholar
  22. 22.
    W.J. Murphy, S.K. Durum and D.L. Longo, Role of neuroendocrine hormones in murine T cell development: growth hormone exerts thymopoietic effects in vivo, J. Immunol. 149:3851 (1992).PubMedGoogle Scholar
  23. 23.
    W.J. Murphy, S.K. Durum, M.R. Anver and D.L. Longo, Immunologic and hematologic effects of neuroendocrine hormones, J. Immunol. 148:3799 (1992).PubMedGoogle Scholar
  24. 24.
    W.J. Murphy, S.K. Durum and D.L. Longo, Human growth hormone promotes engraftment of murine or human T cells in severe combined immunodeficient mice, Proc. Natl. Acad. Sci. USA 89:4481 (1992).PubMedCrossRefGoogle Scholar
  25. 25.
    K.W. Kelley, S. Brief, H.J. Westly, J. Novakofski, P.J. Bechtel, J. Simon and E.B. Walker, GH3 pituitary adenoma cells can reverse thymic aging in rats, Proc. Natl. Acad. Sci. USA 83:5663 (1986).PubMedCrossRefGoogle Scholar
  26. 26.
    M.Y. Li, D.L. Drunke, R. Dantzer and K.W. Kelley, Pituitary epithelial cell implants reverse the accumulation of CD4–CD8-lymphocytes in thymic glands of aged rats, Endocrinology 30:2703 (1992)CrossRefGoogle Scholar
  27. 27.
    H. Selye, “The Stress of Life, McGraw Hill Book Company, New York (1986).Google Scholar
  28. 28.
    S.A. Kaplan, “Clinical Pediatric Endocrinology,” W.B. Saunders Company, USA (1990).Google Scholar
  29. 29.
    M. Preece, Human pituitary growth hormone and Creutzfeldt-Jacob Disease, Horm. Res. 39:95 (1993).PubMedCrossRefGoogle Scholar
  30. 30.
    J.O.L Jorgensen, Human growth hormoen replacement therapy: Pharmacological and clinical aspects, Endocr. Rev. 12:189 (1991).PubMedCrossRefGoogle Scholar
  31. 31.
    O. Westphal, Non-conventional growth hormone treatment in short children, Acta Endocrinol. 128:10 (1993).PubMedGoogle Scholar
  32. 32.
    S. Gupta, S.M. Fikrig and M.S. Noval, Immunological studies in patients with isolated growth hormone deficiency, Clin. Exp. Immunol. 54:87 (1983).PubMedGoogle Scholar
  33. 33.
    V. Abbassi and J.A. Bellanti, Humoral and cell-mediated immunity in growth hormone-deficient children: Effect of therapy with human growth hormone, Pediatr. Res. 19:299 (1985).PubMedCrossRefGoogle Scholar
  34. 34.
    W. Kiess, H. Holtmann, O. Butenandt and R. Eife, Modulation of lymphoproliferation by human growth hormone, Eur. J. Pediatr. 140:47 (1983).PubMedCrossRefGoogle Scholar
  35. 35.
    R. Rapaport, J. Oleske, H. Ahdieh, S. Solomon, C. Delfaus and T. Denny, Suppression of immune function in growth hormone-deficient children during treatment with human growth hormone, J. Pediatr. 109:434 (1986).PubMedCrossRefGoogle Scholar
  36. 36.
    M. Bozzola, M. Cisternino, A. Valtorta, A. Moretta, I. Biscaldi, M. Maghnie, M. De Amici and R.M. Schimpff, Effect of biosynthetic methionyl growth hormone (GH) therapy on the immune function in GH-deficient children, Horm. Res. 31:153 (1989).PubMedCrossRefGoogle Scholar
  37. 37.
    M. Matsuura, Y. Kikkawa, T. Kitagawa and S. Tanaka, Modulation of immunological abnormalities of growth hormone-deficient children by growth hormone treatment, Acta Paediatr. Jpn. 31:53 (1989).PubMedCrossRefGoogle Scholar
  38. 38.
    G.I. Spadoni, P. Rossi, W. Ragno, E. Galli, S. Cianfarani, C. Galasso and B. Boscherini, Immune function in growth hormone-deficient children treated with biosynthetic growth hormone, Acta Paediatr. Scand. 80:75 (1991).PubMedCrossRefGoogle Scholar
  39. 39.
    M. Bozzola, R. Maccario, M. Cisternino, D. De Amici, A. Valtorta, A. Moretta, I. Biscaldi and R.M. Schimpff, Immunological and endocrinological response to growth hormone therapy in short children, Acta Paediatr. Scand. 77:675 (1988).PubMedCrossRefGoogle Scholar
  40. 40.
    J.A. Church, G. Costin and J. Brooks, Immune functions in children treated with biosynthetic growth hormone, J. Pediatr. 115:420 (1989).PubMedCrossRefGoogle Scholar
  41. 41.
    R. Rapaport and J. Oleske, Effect of growth hormone therapy on immune functions, J. Pediatr. 110:663 (1987).Google Scholar
  42. 42.
    R. Rapaport, B. Petersen, K.A. Skuza, M. Heim and S. Goldstein, Immune functions during treatment of growth hormone-deficient children with biosynthetic human growth hormone, Clin. Pediatr. 30:22 (1991).CrossRefGoogle Scholar
  43. 43.
    B.H. Petersen, R. Rapaport, D.P Henry, C. Huseman and W.V. Moore, Effect of treatment with biosynthetic human growth hormone (GH) on peripheral blood lymphocyte populations and function in growth hormone-deficient children, J. Clin. Endocrinol. Metab. 70:1756 (1990).PubMedCrossRefGoogle Scholar
  44. 44.
    R. Rapaport, J. Oleske, H. Ahdieh, K. Skuza, B.K. Holland, M.R. Passannante and T. Denny, Effects of human growth hormone on immune functions: In vitro studies on cells of normal and growth hormone-deficient children, Life Sci. 41, 2319 (1987).PubMedCrossRefGoogle Scholar
  45. 45.
    A. Yoshida, C. Ishioka, H. Kimata and H. Mikawa, Recombinant human growth hormone stimulates B cell immunoglobulin synthesis and proliferation in serum-free medium, Acta Endocrinol. 126, 524 (1992).PubMedGoogle Scholar
  46. 46.
    W. Kiess, H. Doerr, E. Eisl, O. Butenandt and B.H. Belohradsy, Lymphocyte subsets and natural-killer activity in growth hormone deficiency, N. Engl. J. Med. 314:321 (1986).PubMedGoogle Scholar
  47. 47.
    W. Kiess, S. Malozowski, M. Gelato, O. Butenandt, H. Doerr, B. Crisp, E. Eisl, A. Maluish and B.H. Belohradsky, Lymphocyte subset distribution and natural killer activity in growth hormone deficiency before and during short-term treatment with growth hormone releasing hormone, Clin. Immunol. Immunopathol 48:85 (1988).PubMedCrossRefGoogle Scholar
  48. 48.
    D.M. Crist, G.T. Peake, L.T. MacKinnon, W.L. Sibbitt, Jr. and J.C. Kraner, Exogenous growth hormone treatment alters body composition and increases natural killer cell activity in women with impaired endogenous growth hormone secretion, Metabolism 36:1115 (1987).PubMedCrossRefGoogle Scholar
  49. 49.
    M. Bozzola, A. Valtoria, A. Moretta, M. Cisternino, I. Biscaldi and M.R. Schimpff, In vitro and in vivo effect of growth hormone on cytotoxic activity, J. Pediatr. 117:596 (1990).PubMedCrossRefGoogle Scholar
  50. 50.
    M. Vanderschueren-Lodeweyckx, B. Staf, H. Van Den Berghe, E. Eggermont and R. Eeckels, Growth hormone and lymphocyte transformation, Lancet 1:441 (1973).PubMedCrossRefGoogle Scholar
  51. 51.
    A. Astaldi, Jr., B. Yalcin, G. Meardi, G.R. Burgio, R. Merolla and G. Astaldi, Effects of growth hormone on lymphocyte transformation in cell culture, Blut 26:14 (1973).CrossRefGoogle Scholar
  52. 52.
    M. Bozzola, A. Valtorta, A. Moretta, D. Montagna, R. Maccario and G.R. Burgio, Modulating effect of growth hormone (GH) on PHA-induced lymphocyte proliferation, Thymus 12:157 (1988).PubMedGoogle Scholar
  53. 53.
    J.H. Jepson and E.E. McGarry, Hemopoiesis in pituitary dwarfs treated with human growth hormone and testosterone, Blood 39:238 (1972).Google Scholar
  54. 54.
    J. Blatt, S. Wenger, S. Stitely and P.A. Lee, Lack of mitogenic effects of growth hormone on human leukemic lymphoblasts, Eur. J. Pediatr. 146:257 (1987).PubMedCrossRefGoogle Scholar
  55. 55.
    Z. Estrov, R. Meir, Y. Barak, R. Zaizov and Z. Zadik, Human growth hormone and insulin-like growth factor-1 enhance the proliferation of human leukemic blasts, J. Clin. Oncol. 9:394 (1991).PubMedGoogle Scholar
  56. 56.
    D.W. Golde, N. Bersch and C.H. Li, Growth hormone modulation of murine erythroleukemia cell growth in vitro, Proc. Natl. Acad. Sci. USA 75:3437 (1978).PubMedCrossRefGoogle Scholar
  57. 57.
    K.E. Mercola, M.J. Cline and D.W. Golde, Growth hormone stimulation of normal and leukemic human T-lymphocyte proliferation in vitro, Blood 58:337 (1981).PubMedGoogle Scholar
  58. 58.
    S. Merchav, J. Tatarsky and Z. Hochberg, Enhancement of human granulopoiesis in vitro by biosynthetic insulin-like growth factor 1/somatomedin C. and human growth hormone, J. Clin. Invest. 81:791 (1988).PubMedCrossRefGoogle Scholar
  59. 59.
    T.G. Baier, E.W. Jenne, W. Blum, D. Schonberg and K.K.P. Hartmann, Influence of antibodies against IGF-I, insulin or their receptors on proliferation of human acute lymphoblastic leukemia cell lines, Leuk. Res. 16:807 (1992).PubMedCrossRefGoogle Scholar
  60. 60.
    Z. Zadik, Z. Estrov, Y. Karov, T. Hahn and Y. Barak, The effect of growth hormone and IGF-I on clonogenic growth of hematopoietic cells in leukemic patients during active disease and during remission — A preliminary report, J. Pediatr. Endocrinol. 6:79 (1993).PubMedGoogle Scholar
  61. 61.
    S.M. Shalet, Leukaemia in children treated with growth hormone, J. Pediatr. Endocrinol. 6:109 (1993).PubMedCrossRefGoogle Scholar
  62. 62.
    S. Watanabe, S. Mizuno, L.H. Oshima, Y. Tsunematsu, J. Fujimoto and A. Komiyama, Leukemia and other malignancies among GH users, J. Pediatr. Endocrinol. 6:99 (1993).PubMedCrossRefGoogle Scholar
  63. 63.
    G.P. Redmond, R. Rapaport, S. Salisbury, R. David, J. Rao and S. Oberfield, Leukemia in growth hormone deficient (GHD) children who did not receive growth hormone (GH), Pediatr. Res. 31:83A (1992).Google Scholar
  64. 64.
    B. Tedeschi, G.L. Spadoni, M.X. Sanna, P. Vernole, D. Caporossi, S. Cianfarani, B. Nicoletti and B. Boscherini, Increased chromosome fragility in lymphocytes of short normal children treated with recombinant human growth hormone, Hum. Genet. 91:459 (1993).PubMedCrossRefGoogle Scholar
  65. 65.
    J. Rovensky, M. Vigas, J. Lokai, P. Cuncik, P. Lukac and A. Takac, Effect of growth hormone on the metabolic activity of phagocytes of peripheral blood in pituitary dwarfs and acromegaly, Endocrinol. Exp. (Bratisl) 16:128 (1982).Google Scholar
  66. 66.
    J. Rovensky, J. Ferencikova, M. Vigas and P. Lukac, Effect of growth hormone on the activity of some lysosomal enzymes in neutrophilic polymorphonuclear leukocytes of hypopituitary dwarfs, Int. J. Tissue React. 7:153 (1985).PubMedGoogle Scholar
  67. 67.
    C.J. Wiedermann, M. Niedermuhlbichler, D. Geissler, H. Beimpold and H. Braunsteiner, Priming of normal human neutrophils by recombinant human growth hormone, Brit. J. Haematol. 78:19 (1991).CrossRefGoogle Scholar
  68. 68.
    G.L. Spadoni, A. Spagnoli, S. Cianfarani, D. Del Principe, A. Menichelli, S. Di Giulio and B. Boscherini, Enhancement by growth hormone of phorbol diester-stimulated respiratory burst in human polymorphonuclear leukocytes, Acta Endocrinol. (Copenh) 124:589 (1991).Google Scholar
  69. 69.
    C.J. Wiedermann, M. Niedermuhlbichler, H. Beimpold and H. Braunsteiner, In vitro activation of neutrophils of the aged by recombinant human growth hormone, J. Infect. Dis. 164:1017 (1991).PubMedCrossRefGoogle Scholar
  70. 70.
    C.K. Edwards, III, S.M. Ghiasuddin, J.M. Schepper, L.M. Yunger and K.W. Kelley, A newly defined property of somatotropin: Priming of macrophages for production of superoxide anion, Science 239:769 (1988).PubMedCrossRefGoogle Scholar
  71. 71.
    Y.K. Fu, S. Arkins, G. Fuh, B.C. Cunningham, J.A. Wells, S. Fong, M.J. Cronin, R. Dantzer and K.W. Kelley, Growth hormone augments superoxide anion secretion of human neutrophils by binding to the prolactin receptor, J. Clin. Invest. 89:451 (1992).PubMedCrossRefGoogle Scholar
  72. 72.
    Z. Hocherg, P. Hertz, G. Maor, J. Oiknine and M. Aviram, Growth hormone and insulin-like growth factor-I increase macrophage uptake and degradation of low density lipoprotein, Endocrinology 18:430 (199).Google Scholar
  73. 73.
    M.R. Pandian and G.P. Talwar, Effect of growth hormone on the metabolism of thymus and on the immune response against sheep erythrocytes, J. Exp. Med. 134:1095 (1971).PubMedCrossRefGoogle Scholar
  74. 74.
    E. Mocchegiani, P. Paolucci, A. Balsamo, E. Cacciari and N. Fabris, Influence of growth hormone on thymic endocrine activity in humans, Horm. Res. 33:248 (1990).PubMedCrossRefGoogle Scholar
  75. 75.
    J. Timsit, W. Savino, B. Safieh, P. Chanson, M.C. Gagnerault, J.F. Bach and M. Dardenne, Growth hormone and insulin-like growth factor-I stimulate hormonal function and proliferation of thymic epithelial cells, J. Clin. Endocrinol. Metab. 75:183 (1992).PubMedCrossRefGoogle Scholar
  76. 76.
    A.J. Ammann, R.J. Duquesnoy and R.A. Good, Endocrinological studies in ataxia-telangiectasia and other immunological deficiency disease, Clin. Exp. Immunol. 6:587 (1970).PubMedGoogle Scholar
  77. 77.
    A.J. Ammann, W. Sutliff and E. Millinchick, Antibody-mediated immunodefiency in short-limbed dwarfism, J. Pediatr. 84:200 (1974).PubMedCrossRefGoogle Scholar
  78. 78.
    J. Spranger, G.K. Hinkel, H. Stoss, W. Thoenes, D. Eargowski and F. Zepp, Schimke immuno-osseous dysplasia: A newly recognized multisystem disease, J. Pediatr. 119:64 (1991).PubMedCrossRefGoogle Scholar
  79. 79.
    A.D.B. Webster, D. Barnes, C.F. Arlett, A.R. Lehmann and T. Lindahl, Growth retardation and immunodeficiency in a patient with mutations in the DNA ligase 1 gene, Lancet 339:1508 (1992).PubMedCrossRefGoogle Scholar
  80. 80.
    T.A. Fleisher, R.M. White, S. Broder, S.P. Nissley, R.M. Blaese, J.J. Mulvihill, G. Olive and T.A. Waldmann, X-linked hypogammaglobulinemia and isolated growth hormone deficiency, N. Engl. J. Med. 302:1429 (1980).PubMedCrossRefGoogle Scholar
  81. 81.
    K.W. Sitz, A.W. Burks, L.W. Williams, S.F. Kemp and R.W. Steele, Confirmation of X-linked hypogammaglobulinemia with isolated growth hormone deficiency as a disease entity, J. Pediatr. 116:292 (1990).PubMedCrossRefGoogle Scholar
  82. 82.
    V. Monafo, M. Maghnie, L. Terracciano, A. Valtorta, M. Massa and F. Severi, X-linked agammaglobulinemia and isolated growth hormone deficiency, (Case report) Acta Paediatr. Scand. 80:563 (1991).PubMedCrossRefGoogle Scholar
  83. 83.
    M.E. Conley, A.W. Burks, H.G. Herrod and J.A. Puck, Molecular analysis of X-linked agammaglobulinemia with growth hormone deficiency, J. Pediatr. 119:392 (1991).PubMedCrossRefGoogle Scholar
  84. 84.
    N.W. Wilson, J. Daaboul and J.F. Bastian, Association of autoimmunity with IgG2 and IgG4 subclass deficiency in a growth hormone-deficient child, J. Clin. Immunol. 10:330 (1990).PubMedCrossRefGoogle Scholar
  85. 85.
    M.L. Tang and A.S. Kemp, Growth hormone deficiency and combined immunodeficiency, Arch. Dis. Child. 68:231 (1993).PubMedCrossRefGoogle Scholar
  86. 86.
    R. Rapaport, Endocrine abnormalities in children with HIV infections, in: “Management of HIV infections in infants and children,” R. Yogev and E. Connor, eds., Mosby-Year Book Inc. (1992)Google Scholar
  87. 87.
    L.C Alvarez, CO. Dimas, A. Castro, L.G. Rossman, E.F. Vanderlaan and W.P. Vanderlann, Growth hormone in malnutrition, J. Clin. Endocr. 34:400 (1972).PubMedCrossRefGoogle Scholar
  88. 88.
    A.C. Ferguson, Prolonged impairment of cellular immunity in children with intrauterine growth retardation, J. Pediatr. 93:52 (1978).PubMedCrossRefGoogle Scholar
  89. 89.
    D.N. McMurray, R.R. Watson and M.A. Reyes, Effect of renutrition on humoral and cell-mediated immunity in severely malnourished children, Am. J. Clin. Nutr. 34:2117 (1981).PubMedGoogle Scholar
  90. 90.
    A.T. Soliman, A.I. Hassan, M.K. Aref, R.L. Hintz, R.G. Rosenfeld and A.R. Rogol, Serum Insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation, Pediatr. Res. 20:112 (1986).CrossRefGoogle Scholar
  91. 91.
    M.A. Lesniak, J. Roth, P. Gorden and J.R. Gavin, III, Human growth hormone radioreceptor assay using cultured human lymphocytes, Nat. New. Biol. 241:20 (1973).PubMedGoogle Scholar
  92. 92.
    S. Arrenbrecht, Specific binding of growth hormone to thymocytes, Nature 25:255 (1974).CrossRefGoogle Scholar
  93. 93.
    R. Eshet, S. Manheimer, P. Chobsieng and Z. Laron, Human growth hormone receptors in human circulating lymphocytes, Horm. Metab. Res. 7, 352 (1975).PubMedCrossRefGoogle Scholar
  94. 94.
    W. Kiess and O. Butenandt, Specific growth hormone receptors on human peripheral mononuclear cells. Reexpression, identification and characterization, J. Clin. Endocrinol. Metab. 60:740 (1985).PubMedCrossRefGoogle Scholar
  95. 95.
    C. Stewart, S. Clejan, L. Fugler, T. Cheruvanky and P.J. Collipp, Growth hormone receptors in lymphocytes of growth hormone-deficient children, Arch. Biochem. Biophys. 220:309 (1983).PubMedCrossRefGoogle Scholar
  96. 96.
    L.J. Murphy, F. Vrhovsek and L. Lazarus, Identification and characterization of specific growth hormone receptors in cultured human fibroblasts, J. Clin. Endocrinol. Metab. 57:1117 (1983).PubMedCrossRefGoogle Scholar
  97. 97.
    G.A. Werther, K.M. Haynes, D.R. Barnar and M.J. Waters, Visual demonstration of growth hormone rectptors on human growth plate chondrocytes, J. Clin. Endocrinol. Metab. 70:1725 (1990).PubMedCrossRefGoogle Scholar
  98. 98.
    G.A. Werther, K. Haynes and M.J. Waters, Growth hormone (GH) receptors are expressed on human fetal mesenchymal tissues — Indentification of messenger ribonucleir acid and GH binding protein, J. Clin. Endocrinol. Metab. 76:1638 (1993).PubMedCrossRefGoogle Scholar
  99. 99.
    W.N. Rom, P. Basset, G.A. Fells, T. Nukiwa, B.C. Trapnell and R.G. Crystal, Alveolar macrophages release an insulin-like growth factor I-type molecule, J. Clin. Invest. 82:1685 (1988).PubMedCrossRefGoogle Scholar
  100. 100.
    R.G. Rosenfeld and I.A. Dollar, Characterization of the somatomedin-C/insulin like growth factor I (SMC/IGF-I) receptor on cultured human fibroblast monolyers: Regulation of receptor concentrations by SM-C/IGFI and insulin, J. Clin. Endocrinol. Metab. 55:434 (1982).PubMedCrossRefGoogle Scholar
  101. 101.
    C.A. Stuart, R.T. Meehan, L.S. Neale, N.M. Cintron and R.W. Furlanetto, Insulin-like growth factor-I binds selectively to human peripheral blood monocytes and B-lymphocytes, J. Clin. Endocrinol. Metab. 72:1117 (1991).PubMedCrossRefGoogle Scholar
  102. 102.
    B.H. Petersen, P. Barrett, L. Green and R. Rapaport, Flow cytometric detection of growth hormone receptors on human peripheral blood cells, (Presented at the 75th Annual Meeting of the Endocrine Society Annual Meeting, Abstract Book), (1993).Google Scholar
  103. 103.
    S.C. Duck, H.P. Schwartz, G. Costin, R. Rapaport, S. Arslanian, A. Hayek, M. Connors and J. Jarmillo, Subcutaneous growth hormone-releasing hormone therapy in growth hormone deficient children: first year therapy, J. Clin. Endocrinol. Metab. 75:1115 (1992).PubMedCrossRefGoogle Scholar
  104. 104.
    M. Pawlikowski, P. Zelazowski, K. Dohler and H. Stepien, Effects of two neuropeptides, somatoliberin (GRF) and corticoliberin (CRF), on human lymphocyte natural killer activity, Brain. Behav. Immun. 2:50 (1988).PubMedCrossRefGoogle Scholar
  105. 105.
    P. Zelazowski, K.D. Dohler, H. Stepien and M. Pawlikowski, Effect of growth hormone-releasing hormone on human peripheral blood leukocyte Chemotaxis and migration in normal subjects, Neuroendocrinology 50:236 (1989).PubMedCrossRefGoogle Scholar
  106. 106.
    A. Valtorta, A. Moretta, M. Maccario, M. Bozzola and F. Severi, Influence of growth hormone-releasing hormone (GHRH) on phytoemagglutinin-induced lymphocyte activation: Comparison of two synthetic forms, Thymus 18:51 (1991).PubMedGoogle Scholar
  107. 107.
    J.E. Beach, R.C. Smallridge, C.A. Kinzer, E.W. Bernton, J.W. Holaday and H.G. Fein, Rapid release of multiple hormones from rat pituitaries perfused with recombinant interleukin-1, Life Sci. 44:1 (1989).PubMedCrossRefGoogle Scholar
  108. 108.
    E.W. Bernton, J.E. Beach, J.W. Holaday, R.C. Smallridge and H.G. Fein, Release of multiple hormones by a direct action of interleukin-1 on pituitary cells, Science 238:519 (1987).PubMedCrossRefGoogle Scholar
  109. 109.
    V. Rettori, J. Jurcovicova and S.M. McCann, Central action of interleukin-1 in altering the release of TSH, growth hormone, and prolactin in the male rat, J. Neurosci. Res. 18:179 (1987).PubMedCrossRefGoogle Scholar
  110. 110.
    M.B. Atkins, J.A. Gould, M. Allegretta, J.J. Li, R.A. Dempsey, R.A. Rudders, D.R. Parkinson, S. Reichlin and J.W. Mier, Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease, J. Clin. Oncol. 4:1380 (1986).PubMedGoogle Scholar
  111. 111.
    R.M. Schimpff and A.M. Repellin, Production of interleukin-1-alpha and interleukin-2 by 96 mononuclear cells in healthy adults in relation to different experimental conditions and to the presence of growth hormone, Horm. Res. 33:171 (1990).PubMedCrossRefGoogle Scholar
  112. 112.
    R. Rapaport, J. Oleske, S. Schenkman, J. Churchill and C. Kirkpatrick, Growth hormone deficiency: Interleukin-2 (IL2) and immune function, Pediatr. Res. 19:613 (1985).Google Scholar
  113. 113.
    K. Lyson and S.M. McCann, The effect of interleukin-6 on pituitary hormone release in vivo and in vitro, Neuroendocrinology 54:262 (1991).PubMedCrossRefGoogle Scholar
  114. 114.
    N.L. Spangelo, A.M. Judd, P.C. Isakson and R.M. MacLeod, Interleukin-6 stimulates anterior pituitary hormone release in vitro, Endocrinology 125:575 (1989).PubMedCrossRefGoogle Scholar
  115. 115.
    P. Carmeliet, W. Vankelecom, J. Van Damme, A. Billiau and C. Denef, Release of interleukin-6 from anterior pituitary cell aggregates: developmental pattern and modulation by glucocorticoids and forskolin, Neuroendorcinology 53:29 (1991).CrossRefGoogle Scholar
  116. 116.
    B.L. Spangelo, R.M. MacLeod and P.C. Isakson, Production of interleukin-6 by anterior pituitary cells in vitro, Endocrinology 126:582 (1990).PubMedCrossRefGoogle Scholar
  117. 117.
    B.L. Spangelo, P.C. Isakson and R.M. MacLeod, Production of interleukin-6 by anterior pituitary cells is stimulated by increased intracellular adenosine 3′, 5′-monophosphate and vasoactive intestinal peptide, Endocrinology 127:403 (1990).PubMedCrossRefGoogle Scholar
  118. 118.
    B.L. Spangelo, A.M. Judd, P.C. Isakson and R.M. MacLeod, Interleukin-1 stimulates interleukin-6 release from rat anterior pituitary cells in vitro, Endocrinology 128:2685 (1991).PubMedCrossRefGoogle Scholar
  119. 119.
    R.C. Gaillard, D. Turnill, P. Sappino and A.F. Muller, Tumor necrosis factor alpha inhibits the hormonal response of the pituitary gland to hypothalamic releasing factors, Endocrinology 127:101 (1990).PubMedCrossRefGoogle Scholar
  120. 120.
    P.E. Walton, M.J. Cronin, Tumor necrosis factor-alpha inhibits growth hormone secretion from cultured anterior pituitary cells, Endocrinology 125:925 (1989).PubMedCrossRefGoogle Scholar
  121. 121.
    K.W. Kelley, The role of growth hormone in modulation of the immune response, Ann. NY Acad. Sci. 594:95 (1990).PubMedCrossRefGoogle Scholar
  122. 122.
    S.M. McCann, M.C. Gonzalez, L. Milenkovic, S. Karanth, M.C. Aguila, W.L. Dees, K. Lyson and V. Rettori, The effect of stress and infection on pituitary hormone secretion, Neuroendocrinol. Lett. 15:33 (1993).Google Scholar
  123. 123.
    T.J. Merimee, M.B. Grant, C.M. Broder and L.L. Cavalli-Sforza, Insulin-like growth factor secretion by human B-lymphocytes: a comparison of cells from normal and pygmy subjects, J. Clin. Endocrin. Metab. 69:978 (1989).CrossRefGoogle Scholar
  124. 124.
    M.E. Geffner, N. Bersch, B.M. Lippe, R.G. Rosenfeld, R.L. Hintz and D.W. Golde, Growth hormone mediates the growth of T-lymphoblast cell lines via locally generated insulin-like growth factor I, J. Clin. Endocrin. Metab. 71:464 (1990).CrossRefGoogle Scholar
  125. 125.
    N. Hattori, A. Shimatsu, M. Sugita, S. Kumagai and H. Imura, Immunoreactive growth hormone (GH) secretion by human lymphocytes: augmented release by exogenous GH, Biochem. Biophys. Res. Commun. 168:936 (1990).CrossRefGoogle Scholar
  126. 126.
    D.A. Weigent and J.E. Blalock, Expression of growth hormone by lymphocytes, Intern. Rev. Immunol. 4:193 (1989).CrossRefGoogle Scholar
  127. 127.
    D.A. Weigent and J.E. Blalock, Growth hormone releasing hormone production by rat leukocytes, J. Neuroimmunol. 29:1 (1990).PubMedCrossRefGoogle Scholar
  128. 128.
    D.A. Weigent and J.E. Blalock, Growth hormone and the immune system, PNEI Review 3:231 (1990).Google Scholar
  129. 129.
    D.A. Weigent and J.E. Blalock, The production of growth hormone by subpopulations of rat mononuclear leukocytes, Cell. Immunol. 134:001 (1991).CrossRefGoogle Scholar
  130. 130.
    N. Hattori, K. Shimomura, T. Ishihara, K. Moridera, M. Hino, K. Ikekubo and H. Kurahachi, Growth hormone (GH) secretion from human lymphocytes is up-regulated by GH, but not affected by insulin-like growth factor-I, J. Clin. Endocrinol. Metab. 76:937 (1993).PubMedCrossRefGoogle Scholar
  131. 131.
    Symposium on GH-RH, GH and IGF-I: Basic and clinical advances. Final Program and Abstract Book, Serono Symposia, San Diego, CA (USA), December 9–12, 1993.Google Scholar
  132. 132.
    W.D. Denckla, Interactions between age and the neuro-endocrine and immune systems, Fed. Proc. 37:1263 (1978).PubMedGoogle Scholar
  133. 133.
    N. Fabris, W. Pierpaoli and E. Sorkin, Lymphocytes, hormones and aging, Nature 240:557 (1972).PubMedCrossRefGoogle Scholar
  134. 134.
    S. Gillis, R. Kozak, M. Durante and M.E. Weksler, Decreased production of and response to T cell growth factor by lymphocytes from aged humans, J. Clin. Invest. 67:937 (1981).PubMedCrossRefGoogle Scholar
  135. 135.
    D. Rudman, A.G. Feller, H.S. Nagaraj, G.A. Gergans, P.Y. Lalitha, A.F. Goldberg, R.A. Schlenker, L. Cohn, I.W. Rudman and D.E. Mattson, Effects of human growth hormone in men over 60 years old, N. Engl. J. Med. 323:1 (1990).PubMedCrossRefGoogle Scholar
  136. 136.
    E. Corpas, S.M. Harman and M.R. Blackman, Human growth hormone and human aging, Endo. Rev. 14:20 (1993).Google Scholar
  137. 137.
    R.W. Pfaffle, G.E. DiMattia, J.S. Parks, M.R. Brown, J.M. Wit, M. Jansen, H. Van der Nat, J.L. Van Den Brande, M.G. Rosenfeld and H. A. Ingraham, Mutation of the POU-specific domain of Pit-1 and hypoituitarism without pituitary hypoplasia, Science 257:1118 (1992).PubMedCrossRefGoogle Scholar
  138. 138.
    P.A. Kelly, J. Djiane, M.C. Postei-Vinay and M. Edery, The prolactin/growth hormoen receptor family, Endocr. Rev. 12:235 (1991).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Robert Rapaport
    • 1
  1. 1.Department of Pediatrics, Division of Pediatric Endocrinology and MetabolismChildren’s Hospital of New Jersey UMD-New Jersey Medical SchoolNewarkUSA

Personalised recommendations