Endocrine-Immune Interactions in Pituitary Pathology

  • Sylvia L. Asa
  • Kalman Kovacs
Part of the Hans Selye Symposia on Neuroendocrinology and Stress book series (HSSN, volume 3)


The first observations of endocrine-immune interactions were made by pathologists studying mechanisms of disease at the beginning of the twentieth century. They noted the association of thymic involution with Cushing’s syndrome and thymic hyperplasia associated with acromegaly, Graves’ and Addison’s diseases.


Pituitary Adenoma Pituitary Cell Pituitary Hormone Growth Hormone Release Human Pituitary Adenoma 
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.
    E.J. Goetzl and S.P. Sreedharan, Mediators of communication and adaptation in the neuroendocrine and immune systems, FASEB J. 6:2646 (1992).PubMedGoogle Scholar
  2. 2.
    I. Berczi, Neurohormonal immunoregulation, Endocr. Pathol. 1:197 (1990).CrossRefGoogle Scholar
  3. 3.
    I. Berczi, The role of prolactin in the pathogenesis of autoimmune disease, Endocr. Pathol. 4:178 (1993).CrossRefGoogle Scholar
  4. 4.
    E. Nagy and I. Berczi, Immunodeficiency in hypophysectomized rats, Acta Endocrinol. (Copenh) 89:530 (1978).Google Scholar
  5. 5.
    I. Berczi, E. Nagy, K. Kovacs and E. Horvath, Regulation of humoral immunity in rats by pituitary hormones, Acta Endocrinol. (Copenh) 98:506 (1981).Google Scholar
  6. 6.
    I. Berczi and E. Nagy, A possible role of prolactin in adjuvant arthritis, Arthritis Rheum. 25:591 (1982).PubMedCrossRefGoogle Scholar
  7. 7.
    I. Berczi, E. Nagy, S.L. Asa and K. Kovacs, Pituitary hormones and contact sensitivity in rats, Allergy 38:325 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    I. Berczi, E. Nagy, S.L. Asa and K. Kovacs, The influence of pituitary hormones on adjuvant arthritis, Arthritis Rheum. 27:682 (1984).PubMedCrossRefGoogle Scholar
  9. 9.
    E. Nagy, I. Berczi and H.G. Friesen, Regulation of immunity in rats by lactogenic and growth hormones, Acta Endocrinol. (Copenh) 102:351 (1983).Google Scholar
  10. 10.
    I. Berczi and E. Nagy, Effects of hypophysectomy on immune function, in: “Psychoneurniroimmunology,” 2nd F.d., R. Ader, D.L. Feiten and N. Cohen, eds., Academic Press, Inc., (1991).Google Scholar
  11. 11.
    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 hypopituitarism without pituitary hypoplasia, Science 257:1118 (1992).PubMedCrossRefGoogle Scholar
  12. 12.
    K. Tatsumi, K. Miyai, T. Notomi, K. Kaibe, N. Amino, Y. Mizuno and H. Kohno, Cretinism with combined hormone deficiency caused by a mutation in the Pit-1 gene, Nature Gen. 1:56 (1992).CrossRefGoogle Scholar
  13. 13.
    S.L. Asa, K. Kovacs, A. Halasz, A.M. Toszegi and P. Szucs, Absence of somatotroph,lactotrophs, and thyrotrophs in the pituitary of two dwarfs with hypothyroidism: deficiency of pituitary transcription factor-1? Endocr. Pathol. 3:93 (1992).CrossRefGoogle Scholar
  14. 14.
    S. Radovick, M. Nations, Y. Du, L.A. Berg, B.D. Weintraub and F.E. Wondisford, A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency, Science 257:1115 (1992).PubMedCrossRefGoogle Scholar
  15. 15.
    T. Tanaka, R.P.C. Shiu, P.W. Gout, C.T. Beer, R.L. Noble and H.G. Friesen, A new sensitive and specific bioassay for lactogenic hormones: measurement of prolactin and growth hormone in human serum, J. Clin. Endocrinol. Metab. 51:1058 (1980).PubMedCrossRefGoogle Scholar
  16. 16.
    I. Berczi and E. Nagy, The effect of prolactin and growth hormone on hemolymphopoietic tissue and immune function, in: “Hormones and Immunity,” I. Berczi and K. Kovacs, eds., MTP Press, Lancaster, UK (1987).Google Scholar
  17. 17.
    K.W. Kelley, Growth hormone, lymphocytes and macrophages, Biochem. Pharmacol. 38:705 (1989).PubMedCrossRefGoogle Scholar
  18. 18.
    K.W. Kelley, Growth hormone in immunobiology, in: “Psychoneuroimmunology,” 2nd Ed., R. Ader, D.L. Feiten and N. Cohen, eds., Academic Press, New York (1991).Google Scholar
  19. 19.
    D.A. Weigent, J.B. Baxter, W.E. Wear, L.R. Smith, K.L. Bost and J.E. Blalock, Production of immunoreactive growth hormone by mononuclear leukocytes, FASEB J. 2:2812 (1988).PubMedGoogle Scholar
  20. 20.
    S. Varma, P. Sabharwal, J.F. Sheridan and W.B. Malarkey, Growth hormone secretion by human peripheral blood mononuclear cells detected by an enzyme-linked immunoplaque assay, J. Clin. Endocrinol. Metab. 76:49 (1993).PubMedCrossRefGoogle Scholar
  21. 21.
    E. Nagy and I. Berczi, Prolactin and contact sensitivity, Allergy 36:429 (1981).PubMedCrossRefGoogle Scholar
  22. 22.
    E. Nagy, I. Berczi, G.E. Wren, S.L. Asa and K. Kovacs, Immunomodulation by bromocriptine, Immunopharmacology 6:231 (1983).PubMedCrossRefGoogle Scholar
  23. 23.
    R.C. Rowe, E.A. Cowden, C. Faiman and H.G. Friesen, Correlation of Nb2 bioassay and radioimmunoassay values for human serum prolactin, J. Clin. Endocrinol. Metab. 57:942 (1983).PubMedCrossRefGoogle Scholar
  24. 24.
    A. Bateman, A. Singh, T. Kral and S. Solomon, The immune-hypothalamic-pituitary-adrenal axis, Endocr. Rev. 10:92 (1989).PubMedCrossRefGoogle Scholar
  25. 25.
    K. Karalis, H. Sano, J. Redwine, S. Listwak, R.L. Wilder and G.P. Chrousos, Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo, Science 254:421 (1991).PubMedCrossRefGoogle Scholar
  26. 26.
    N.J. Olsen, W.E. Nicholson, C.R. DeBold and D.N. Orth, Lymphocyte-derived adrenocorticotropin is insufficient to stimulate adrenal steroidogenesis in hypophysectomized rats, Endocrinology 130:2113 (1992).PubMedCrossRefGoogle Scholar
  27. 27.
    A.G. DuPont, G. Somers, A.C. Van Steirteghem, F. Warson and L. Vanhaelst, Ectopic adrenocorticotropin production: disappearance after removal of inflammatory tissue, J. Clin. Endocrinol. Metab. 58:654 (1984).PubMedCrossRefGoogle Scholar
  28. 28.
    H. Kotzman, M. Clodi, T. Svoboda, R. Deyssig and A. Luger, Cytokine production and natural killer cell activity in patients with prolactinomas and acromegaly, Endocrinology (suppl.):68, (1992) (Abstract No. 68).Google Scholar
  29. 29.
    R.E. Palmiter, R.L. Brinster, R.E. Hammer, M.E. Trumbauer, N.G. Rosenfeld, N.C. Birhberg and R.M. Evans, Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes, Nature 300:613 (1982).CrossRefGoogle Scholar
  30. 30.
    E.M. Sternberg, W.S. Young III and R. Bernardini, A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats, Proc. Natl. Acad. Sci. USA 86:4771 (1989).PubMedCrossRefGoogle Scholar
  31. 31.
    R. Fassler, K. Schauenstein, G. Kremer, S. Schwarz and G. Wick, Elevation of corticosteroid binding globulin in obese strain (OS) chickens: possible implications for the distributed immunoregulation and the development of spontaneous autoimmune thyroiditis, J. Immunol. 136:3657 (1986).PubMedGoogle Scholar
  32. 32.
    I.C. Chikanza, P. Petrou, G. Kingsley, G.P. Chrousos and G.S. Panayi, Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis, Arthritis Rheum. 35:1281 (1992).PubMedGoogle Scholar
  33. 33.
    A. Catania, L. Airaghi, M.G. Manfredi, M.C. Vivirito and I.M. Lipton, Relations among plasma concentrations of alpha-MSH, ACTH and cytokines in AIDS patients, Endocrinology (Suppl.):199 (1992) (Abstract No. 59).Google Scholar
  34. 34.
    S. Reichlin, Neuroendocrine-immune interactions, N. Engl. J. Med. 329:1246 (1993).PubMedCrossRefGoogle Scholar
  35. 35.
    B.L. Spangelo and R.M. MacLeod, The role of immunopeptides in the regulation of anterior pituitary hormone release, Trends Endocrinol. Metab. 2:408 (1990).Google Scholar
  36. 36.
    E.W. Bernton, J.E. Beach, J.W. Holaday, R.C. Smallridge and N.G. Fein, Release of multiple hormones by a direct action of interleukin-1 on pituitary cells, Science 238:519 (1987).PubMedCrossRefGoogle Scholar
  37. 37.
    P.E. Walton and M J. Cronin, Tumor necrosis factor-a and interferon-gamma reduce prolactin release in vitro, Am. J. Physiol. 259:E672 (1990).Google Scholar
  38. 38.
    H. Vankelecom, M. Andries, A. Billiau and C. Denef, Evidence that folliculo-stellate cells mediate the inhibotyory effect of interferon- on hormone secretion in rat anterior pituitary cell cultures, Endocrinology 130:3537 (1992).PubMedCrossRefGoogle Scholar
  39. 39.
    H. Muller, E. Hammes, C. Hiemke and G. Hess, Interferon-alpha-2-induced stimulation of ACTH and Cortisol secretion in man, Neuroendocrinology 54:499 (1991).PubMedCrossRefGoogle Scholar
  40. 40.
    C.J. Wiedermann, W. Vogel, H. Tilg, W.J. Wiedermann, M. Herold, U. Zilian, T. Wohlfarter, M. Gruber and H. Braunsteiner, Suppression of thyroid function by interferon-alpha2 in man, Arch. Pharmacol. 343:665 (1991).CrossRefGoogle Scholar
  41. 41.
    W.B. Malarkey and B.J. Zvara, Interleukin-1b and other cytokines stimulate adrenocorticotropin release from cultured pituitary cells of patients with Cushing’s disease, J. Clin. Endocrinol. Metab. 69:196 (1989).PubMedCrossRefGoogle Scholar
  42. 42.
    S.L. Asa, K. Kovacs and S. Melmed, The hypothalamic-pituitary axis, in: “The Pituitary,” S. Melmed, ed., Blackwell Scientific Publications Inc., Boston (1994) (in press).Google Scholar
  43. 43.
    H.N. Kamerow, A. Perchick and D.E. Burstein, Immunocytochemical detection of cyclin, a proliferation-associated protein, in cytologic preparations, Acta Cytol. 35:491 (1991).PubMedGoogle Scholar
  44. 44.
    L.C. Payne, F. Obal Jr., M.R. Opp and J.M. Krueger, Stimulation and inhibition of growth hormone secretion by interleukin-lb: The involvement of growth hormone-releasing hormone, Neuroendocrinology 56:118 (1992).PubMedCrossRefGoogle Scholar
  45. 45.
    J.N. Peisen, J.W. Bordeaux, K.J. McDonnell, D.E. Tracey and M.D. Lumpkin, Effects of interleukin-1 (IL-1) and IL-1 receptor antagonist on growth hormone releasing hormone and somatostatin secretion from rat hypothalamus, Endocrinology (suppl.):394 (1992) (Abstract No. 137).Google Scholar
  46. 46.
    D.E. Scarborough, S.L. Lee, CA. Dinarello and S. Reichlin, Interleukin-lb stimulates somatostatin biosynthesis in primary cultures of fetal rat brain, Endocrinology 124:549 (1989).PubMedCrossRefGoogle Scholar
  47. 47.
    Y. Naito, J. Fukata, T. Tominaga, Y. Masui, Y. Hirai, N. Murakami, S. Tamai, K. Mori and H. Imura, Adrenocorticotropic hormone-releasing activities of interleukins in a homologous in vivo system, Biochem. Biophys. Res. Commun. 164:1262 (1989).PubMedCrossRefGoogle Scholar
  48. 48.
    F. Sweep, C. Rijinkels and A. Hermus, Activation of the hypothalamus-pituitary-adrenal axis by cytokines, Acta Endocrinol. (Copenh) 125:84 (1991).PubMedGoogle Scholar
  49. 49.
    J. Fukata, T. Usui, Y. Naitoh, Y. Nakai and H. Imura, Effects of recombinant human interleukin-lα, -1β , 2 and 6 on ACTH synthesis and release in the mouse pituitary tumour cell line AtT-20, J. Endocrinol. 122:33 (1989).PubMedCrossRefGoogle Scholar
  50. 50.
    B.M. Sharp, S.G. Matta, P.K. Peterson, R. Newton, C. Chao and K. Mcallen, Tumor necrosis factor-a is a potent ACTH secretagogue: Comparison to interleukin-lb, Endocrinology 124:3131 (1989).PubMedCrossRefGoogle Scholar
  51. 51.
    R. Sapolsky, C. Rivier, G. Yamamoto, P. Plotsky and W. Vale, Interleukin-1 stimulates the secretioin of hypothalamic corticotropin-releasing factor, Science 238:522 (1981).CrossRefGoogle Scholar
  52. 52.
    S. Tsagarakis, G. Gillies, L.H. Rees, M. Besser and A. Grossman, Interleukin-1 directly stimulates the release of corticotrophin releasing factor from rat hypothalamus, Neuroendocrinology 49:98 (1989).PubMedCrossRefGoogle Scholar
  53. 53.
    F. Berkenbosch, J. Van Oers, A. Del Rey, F. Tilders and H. Besedovsky, Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1, Science 238:524 (1987).PubMedCrossRefGoogle Scholar
  54. 54.
    E.T. Cunningham, Jr. and E.B. DeSouza, Interleukin 1 receptors in the brain and endocrine tissues, Immunol. Today 14:1171 (1993).Google Scholar
  55. 55.
    H. Kobayashi, J. Fukata, T. Tominaga, N. Murukami, M. Fukushima, O. Ebisui, H. Segawa, Y. Nakai and H. Imura, Regulation of interleukin-1 receptors on AtT-20 mouse pituitary tumour cells, FEBS Lett. 298:100 (1991).CrossRefGoogle Scholar
  56. 56.
    E.L. Webster, D.E. Tracey and E.B. De Sousza, Upregulation of interleukin-1 receptors in mouse AtT-20 pituitary tumor cells following treatment with corticotropin-releasing factor, Endocrinology 129:2796 (1991).PubMedCrossRefGoogle Scholar
  57. 57.
    L. Xia, E. Shalts, Y.J. Feng and M. Ferin, Modulation by the ovarian steroids of the effects of interleukin-1 alpha on luteinizing hormone in the ovariectomized rhesus monkey, Endocrinology (suppl.):354 (1992) (Abstract No. 210).Google Scholar
  58. 58.
    S. Rivest and C. Rivier, Inhibitory influence of interleukin-1b on c-fos expression located in the LHRH neurons and hypothalamic LHRH release during proestrus in rats, Endocrinology (suppl.):258 (1992) (Abstract No. 825).Google Scholar
  59. 59.
    S. Karanth and S.M. McCann, Anterior pituitary hormone control by interleukin 2, Proc. Natl. Acad. Sci. USA 88:2961 (1991).PubMedCrossRefGoogle Scholar
  60. 60.
    S. Karanth, M.C. Aguila and S.M. McCann, The influence of interleukin-2 on the release of somatostatin and growth hormone-releasing factor by the mediobasal hypothalamus, Endocrinology (suppl.):397 (1992) (Abstract No. 1383).Google Scholar
  61. 61.
    E. Arzt, R. Buric, G. Stelzer, J. Stalla, J. Sauer, U. Renner and G.K. Stalla, Interleukin involvement in anterior pituitary cell growth regulation: Effects of IL-2 and IL-6, Endocrinology 132:459 (1993).PubMedCrossRefGoogle Scholar
  62. 62.
    G. Wick, Y. Hu, S. Schwarz and G. Kroemer, Immunoendocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune diseases, Endocr. Rev. 14:539 (1993).PubMedGoogle Scholar
  63. 63.
    K. Lyson and J.M. Lipton, Alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone inhibit interleukin-6-induced corticotropin-releasing factor release in vitro, Endocrinology (suppl.):380 (1992) (Abstract No. 1315).Google Scholar
  64. 64.
    B.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
  65. 65.
    M. Yamaguchi, M. Sakata, N. Matsuzaki, K. Koike, A. Miyake and O. Tanizawa, Induction by tumor necrosis factor-alpha of rapid release of immmunoreactive and bioactive luteinizing hormone from rat pituitary cells in vitro, Neuroendocrinology 52:468 (1990).PubMedCrossRefGoogle Scholar
  66. 66.
    P. Carmeliet, H. 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, Neuroendocrinology 53:294 (1991).CrossRefGoogle Scholar
  67. 67.
    B. Velkeniers, R. Hooghe, Y. Hongqu, et al, Interleukin-6 in the pituitary gland, J. Endocrinol. Invest. 14 (suppl.4):189 (1991) (Abstract).Google Scholar
  68. 68.
    B.L. Spangelo and R.M. Wright RM, Arachadonic acid stimulates interleukin-6 release from rat anterior pituitary cells in vitro, Endocrinology (suppl.):179 (1992) (Abstract No. 512).Google Scholar
  69. 69.
    H. Vankelecom, P. Carmeliet, J. van Damme, A. Billiau and C. Denef, Production of interleukin-6 by folliculo-stellate cells of the anterior pituitary gland in a histiotypic cell aggregate culture system, Neuroendocrinology 49:102 (1989).PubMedCrossRefGoogle Scholar
  70. 70.
    H. Matsumoto, C. Koyama, T. Sawada, K. Koike, K. Hirota, A. Miyake, A. Arimura and I. Inoue, Pituitary folliculo-stellate-like cell Une (TtT/GF) responds to novel hypophysiotropic peptide (pituitary adenylate cyclase-activating peptide), showing increased adenosine3′,5′-monophosphate and interleukin-6 secretion and cell proliferation, Endocrinology 133:2150 (1993).PubMedCrossRefGoogle Scholar
  71. 71.
    S.L. Asa, K. Kovacs snf S. Melmed, The hypothalamic-pituitary axis, in: “The pituitary,” S. Melmed, ed., Blackwell Scientific Publications, Boston (1994) (in press).Google Scholar
  72. 72.
    T.H. Jones, S. Justice, A. Price and K. Chapman, Interleukin-6 secreting human pituitary adenomas in vitro, J. Clin. Endocrinol. Metab. 73:207 (1991).PubMedCrossRefGoogle Scholar
  73. 73.
    B. Velkeniers, P. Vergani, J. Trouillas, J. D’Haens, R.J. Hooghe and E.L. Hooghe-Peters, Expression of IL-6 mRNA in normal rat and human pituitaries and in human pituitary adenomas, J. Histochem. Cytochem. 42:67 (1994).PubMedCrossRefGoogle Scholar
  74. 74.
    S. Tsagarakis, G. Kontogeorgos, P. Giannou, N. Thalassinos, J. Wooley, G.M. Besser and A. Grossman, Interleukin-6 a growth promoting cytokine, is present in human pituitary adenomas: an immunocytochemical study, Clin. Endocrinol. (Oxf) 37:163 (1992).CrossRefGoogle Scholar
  75. 75.
    E. Arzt, U. Renner, K. Lechner, G. Stelzer, O.A. Muller and G.K. Stalla, Expression of interleukin-2 mRNA in human corticotropic adenoma cells in vitro, J. Endocrinol. Invest. 14 (suppl.4):188 (1991) (Abstract).Google Scholar
  76. 76.
    L. Ramyar, S.L. Asa, W. Singer and K. Kovacs, Cytokines do not alter hormone release by human pituitary adenomas in vitro, Endocrinology (suppl.):(1993) (Abstract No. 1569).Google Scholar
  77. 77.
    S.L. Asa, J.M. Bilbao, K. Kovacs, R.G. Josse and K. Kreines, Lymphocytic hypophysitis of pregnancy resulting in hypopituitarism: a distinct clinicopathologic entity, Ann. Intern. Med. 95:166 (1981).PubMedCrossRefGoogle Scholar
  78. 78.
    F. Cosman, K.D. Post, D.A. Holub and S.L. Wardlaw, Lymphocytic hypophysitis. Report of 3 new cases and review of the literature, Medicine 68:240 (1989).PubMedCrossRefGoogle Scholar
  79. 79.
    P. Crock, M. Salvi, A. Miller, J. Wall and H. Guyda, Detection of anti-pituitary autoantibodies by immunoblotting, J. Immunol. Methods 162:31 (1993).PubMedCrossRefGoogle Scholar
  80. 80.
    A. Pouplard, Pituitary autoimmunity, Horm. Res. 16:289 (1982).PubMedCrossRefGoogle Scholar
  81. 81.
    G.F. Bottazzo and D. Doniach, Pituitary autoimmunity: A review, J. Royal Soc. Med. 71:433 (1978).Google Scholar
  82. 82.
    W.A. Scherbaum, M. Gluck, U. Schrell, R. Fahlbusch and E.F. Pfeiffer, Autoantibodies to pituitary corticotropin-producing cells: Possible marker for unfavourable outcome after pituitary microsurgery for Cushing’s disease, Lancet 1:1394 (1987).PubMedCrossRefGoogle Scholar
  83. 83.
    M.D. Jensen, B.S. Handwerger, B.W. Scheithauer, P.C. Carpenter, R. Mirakian and P.M. Banks, Lymphocytic hypophysitis with isolated corticotropin deficiency, Ann. Intern. Med. 105:200 (1986).PubMedCrossRefGoogle Scholar
  84. 84.
    A.L. Barkan, R.P. Kelch and J.C. Marshall, Isolated gonadotrope failure in the polyglandular autoimmune syndrome, N. Engl. I. Med. 312:1535 (1985).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Sylvia L. Asa
    • 1
  • Kalman Kovacs
    • 1
  1. 1.Department of Pathology, Mount Sinai Hospital and St. Michael’s HospitalUniversity of TorontoTorontoCanada

Personalised recommendations