problendoПроблемы ЭндокринологииProblems of Endocrinology0375-96602308-1430Endocrinology Research Centre10.14341/probl201359130-34problendo-4535Research ArticleСтатьиArticlesВзаимосвязь соматотропной функции гипофиза и иммунной системы и их роль в развитии неоплазийThe relationship between the pituitary somatotrophic function and the immune system, its role in the development of neoplasiaDogadinS A-DudinaM Amargo85_@bk.ruSavchenkoA A-201315022013591ТОМ 59, №1 (2013)3034Copyright © Dogadin S.A., Dudina M.A., Savchenko A.A., 20132013Dogadin S.A., Dudina M.A., Savchenko A.A.Dogadin S.A., Dudina M.A., Savchenko A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.probl-endojournals.ru/jour/article/view/4535

Представлены данные о связи гормона роста (ГР) с иммунной системой. Обсуждается влияние ростовых факторов на популяционный и субпопуляционный состав CD-экспрессирующих лимфоцитов, функциональную активность клеток иммунной системы, модуляцию апоптоза. Подробно описана роль нарушений соматотропной функции гипофиза и иммунной системы в генезе развития неопластических процессов. Изменения в иммунной системе при хронической гиперсекреции ростовых факторов, а также тесные иммуноэндокринные взаимодействия представляются важными факторами патогенеза нео­плазий, непосредственно влияющими на выживаемость больных при акромегалии.

The present review is focused on the relationship between growth hormone (GH) production and the state of the immune system. The influence of growth factors on the population and subpopulation composition of CD-expressing lymphocytes, functional activity of immune cells, and apoptosis is discussed. The detailed description of the role of disturbances in the pituitary somatotrophic function and the concomitant immune disorders is presented with special reference to the development of neoplastic processes. Changes in the immune system of the patients with chronic hypersecretion of growth factors are described. Tight interactions between the immune and endocrine systems appear to greatly contribute to tumour pathogenesis and have direct effect on the survivorship rate among the patients with acromegaly.

гормон ростаинсулиноподобный фактор роста I типаиммунная системанеоплазииgrowth hormoneinsulin-like growth factor Iimmune systemneoplasiaReferencesFerone D., van Hagen P.M., van Koetsveld P.M., Zuijderwijk J., Mooy D.M., Lichtenauer-Kaligis E.G., Colao A., Bogers A.J., Lombardi G., Lamberts S.W., Hofland L.J. In vitro characterization of somatostatin receptors in the human thymus and effects of somatostatin and octreotide on cultured thymic epithelial cells. Endocrinol 1999; 140: 1: 373-380.Ferone D., van Hagen P.M., van Koetsveld P.M., Zuijderwijk J., Mooy D.M., Lichtenauer-Kaligis E.G., Colao A., Bogers A.J., Lombardi G., Lamberts S.W., Hofland L.J. In vitro characterization of somatostatin receptors in the human thymus and effects of somatostatin and octreotide on cultured thymic epithelial cells. Endocrinol 1999; 140: 1: 373-380.Giovannucci E. Insulin-like growth factor-I and binding protein-3 and risk of cancer. Horm Res 1999; 51: 3: 34-41.Giovannucci E. Insulin-like growth factor-I and binding protein-3 and risk of cancer. Horm Res 1999; 51: 3: 34-41.Thellin O., Coumans B., Devos S., Hooghe-Peters E.L., Zorzi W., Igout A., Heinen E., Hooghe R. Limited effects of placental and pituitary growth hormone on cytokine expression in vitro. Eur Cytokine Netw 2000; 11: 3: 452-455.Thellin O., Coumans B., Devos S., Hooghe-Peters E.L., Zorzi W., Igout A., Heinen E., Hooghe R. Limited effects of placental and pituitary growth hormone on cytokine expression in vitro. Eur Cytokine Netw 2000; 11: 3: 452-455.Kooijman R., Hooghe-Peters E., Hooghe R. Prolactin, growth hormone and insulin-like growth factor-I in the immune system. Adv Immunol 1996; 63: 377-454.Kooijman R., Hooghe-Peters E., Hooghe R. Prolactin, growth hormone and insulin-like growth factor-I in the immune system. Adv Immunol 1996; 63: 377-454.Robbins K., McCabe S., Scheiner T. Immunological effects of insulin-like growth factor-I-enhancement of immunoglobulin synthesis. Clin Exp Immunol 1994; 95: 2: 337-342.Robbins K., McCabe S., Scheiner T. Immunological effects of insulin-like growth factor-I-enhancement of immunoglobulin synthesis. Clin Exp Immunol 1994; 95: 2: 337-342.Long E., Huynh H., Zhao X. Involvement of insulin-like growth factor-1 and its binding proteins in proliferation and differentiation of murine bone marrow-derived macrophage precursors. Endocrinol 1998; 9: 185-192.Long E., Huynh H., Zhao X. Involvement of insulin-like growth factor-1 and its binding proteins in proliferation and differentiation of murine bone marrow-derived macrophage precursors. Endocrinol 1998; 9: 185-192.Hansen T., Thiel S., Dall R., Rosenfalck A.M., Trainer P., Flyvbjerg A., Jørgensen J.O., Christiansen J.S. GH strongly acts serum concentrations of mannan-binding lectin: evidence for a new IGF-I independent immunomodulatory effect of GH. J Clin Endocrinol Metab 2001; 86: 11: 5383-5388.Hansen T., Thiel S., Dall R., Rosenfalck A.M., Trainer P., Flyvbjerg A., Jørgensen J.O., Christiansen J.S. GH strongly acts serum concentrations of mannan-binding lectin: evidence for a new IGF-I independent immunomodulatory effect of GH. J Clin Endocrinol Metab 2001; 86: 11: 5383-5388.Colao A., Balzano A., Ferone D., Panza N., Grande G., Marzullo P., Bove A., Iodice G., Merola B., Lombardi G. Increased prevalence of colonic polyps and altered lymphocyte subset pattern in the colonic lamina propria in acromegaly. Clin Endocrinol (Oxford) 1997; 47: 23-28.Colao A., Balzano A., Ferone D., Panza N., Grande G., Marzullo P., Bove A., Iodice G., Merola B., Lombardi G. Increased prevalence of colonic polyps and altered lymphocyte subset pattern in the colonic lamina propria in acromegaly. Clin Endocrinol (Oxford) 1997; 47: 23-28.Mocchegiani E., Paolucci P., Balsamo A., Cacciari E., Fabris N. Influence of growth hormone on thymic endocrine activity in humans. Horm Res 1990; 33: 6: 248-255.Mocchegiani E., Paolucci P., Balsamo A., Cacciari E., Fabris N. Influence of growth hormone on thymic endocrine activity in humans. Horm Res 1990; 33: 6: 248-255.Dorshkind D., Horseman D., Dorshkind K., Horseman N.D. The roles of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormones in lymphocyte development and function: insights from genetic models of hormone and hormone receptor deficiency. Endocr Rev 2000; 21: 3: 292-312.Dorshkind D., Horseman D., Dorshkind K., Horseman N.D. The roles of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormones in lymphocyte development and function: insights from genetic models of hormone and hormone receptor deficiency. Endocr Rev 2000; 21: 3: 292-312.Fajas L., Auboeuf D., Raspe E., Schoonjans K., Lefebvre A.M., Saladin R., Najib J., Laville M., Fruchart J.C., Deeb S., Vidal-Puig A., Flier J., Briggs M.R. The organization, promoter analysis, and expression of the human PPARgamma gene. J Biol Chem 1997; 272: 30: 18779-18789.Fajas L., Auboeuf D., Raspe E., Schoonjans K., Lefebvre A.M., Saladin R., Najib J., Laville M., Fruchart J.C., Deeb S., Vidal-Puig A., Flier J., Briggs M.R. The organization, promoter analysis, and expression of the human PPARgamma gene. J Biol Chem 1997; 272: 30: 18779-18789.Bogazzi F., Ultimieri F., Raggi F., Russo D., Vanacore R., Guida C., Brogioni S., Cosci C., Gasperi M., Bartalena L., Martino E. Growth hormone inhibits apoptosis in human colonic cancer cell lines: antagonistic effects of peroxisome proliferator activated receptor - ligands. Endocrinol 2004; 145: 7: 3353-3362.Bogazzi F., Ultimieri F., Raggi F., Russo D., Vanacore R., Guida C., Brogioni S., Cosci C., Gasperi M., Bartalena L., Martino E. Growth hormone inhibits apoptosis in human colonic cancer cell lines: antagonistic effects of peroxisome proliferator activated receptor - ligands. Endocrinol 2004; 145: 7: 3353-3362.Renehan A., Brennan B. Acromegaly, growth hormone and cancer risk. Best Pract Res Clin Endocrinol Metab 2008; 22: 4: 639-657.Renehan A., Brennan B. Acromegaly, growth hormone and cancer risk. Best Pract Res Clin Endocrinol Metab 2008; 22: 4: 639-657.Moon H.D., Simpson M.E., Li C.H., Evans H.M. Neoplasms in rats treated with pituitary growth hormone I. pulmonary and lymphatic tissues. Cancer Res 1950; 14: 297-308.Moon H.D., Simpson M.E., Li C.H., Evans H.M. Neoplasms in rats treated with pituitary growth hormone I. pulmonary and lymphatic tissues. Cancer Res 1950; 14: 297-308.Pollak N.M., Schernhammer E.S., Hankinson S.E. Insulin-like growth factors and neoplasia. Nat Rev Cancer 2004; 4: 7: 505-518.Pollak N.M., Schernhammer E.S., Hankinson S.E. Insulin-like growth factors and neoplasia. Nat Rev Cancer 2004; 4: 7: 505-518.Adenis A., Peyrat J., Hecquet B., Delobelle A., Depadt G., Quandalle P., Bonneterre J., Demaille A. Type I insulin-like growth factor receptors in human colorectal cancer. Eur J Can 1995; 31a: 1: 50-55.Adenis A., Peyrat J., Hecquet B., Delobelle A., Depadt G., Quandalle P., Bonneterre J., Demaille A. Type I insulin-like growth factor receptors in human colorectal cancer. Eur J Can 1995; 31a: 1: 50-55.Van Buul-Offers S.C., Kooijman R. The role of growth hormone and insulin-like growth factors in the immune system. Cell Mol Life Sci 1998; 54: 10: 1083-1094.Van Buul-Offers S.C., Kooijman R. The role of growth hormone and insulin-like growth factors in the immune system. Cell Mol Life Sci 1998; 54: 10: 1083-1094.Colao A., Marzullo P., Spiezia S., Ferone D., Giaccio A., Cerbone G., Pivonello R., Di Somma C., Lombardi G. Effect of Growth Hormone (GH) and Insulin-Like Growth Factor I on Prostate Diseases: An Ultrasonographic and Endocrine Study in Acromegaly, GH Deficiency, and Healthy Subjects. J Clin Endocrinol Metab 1998; 84: 6: 1986-1991.Colao A., Marzullo P., Spiezia S., Ferone D., Giaccio A., Cerbone G., Pivonello R., Di Somma C., Lombardi G. Effect of Growth Hormone (GH) and Insulin-Like Growth Factor I on Prostate Diseases: An Ultrasonographic and Endocrine Study in Acromegaly, GH Deficiency, and Healthy Subjects. J Clin Endocrinol Metab 1998; 84: 6: 1986-1991.Khorram O., Garthwaite M., Golos T. The influence of aging and sex hormones on expression of growth hormone-releasing hormone (GHRH) in the human immune system. J Clin Endocrinol Metab 2001; 86: 7: 3157-3161.Khorram O., Garthwaite M., Golos T. The influence of aging and sex hormones on expression of growth hormone-releasing hormone (GHRH) in the human immune system. J Clin Endocrinol Metab 2001; 86: 7: 3157-3161.Siegel G., Tomer Y. Is there an association between acromegaly and thyroid carcinoma? A critical review of the literature. Endocrinol Res 2005; 31: 1: 51-58.Siegel G., Tomer Y. Is there an association between acromegaly and thyroid carcinoma? A critical review of the literature. Endocrinol Res 2005; 31: 1: 51-58.Colao A., Barkan A., Scarpa R. Growth hormone/insulin-like growth factor-I system and connective tissues: basic aspects and clinical implications. Rheum Dis Clin N Am 2005; 31: 1: 29-42.Colao A., Barkan A., Scarpa R. Growth hormone/insulin-like growth factor-I system and connective tissues: basic aspects and clinical implications. Rheum Dis Clin N Am 2005; 31: 1: 29-42.Furstenberger G., Sann H. Insulin-like growth factors and cancer. Lancet Oncol 2002; 3: 298-302.Furstenberger G., Sann H. Insulin-like growth factors and cancer. Lancet Oncol 2002; 3: 298-302.Jeay S., Sonenshein G., Postel-Vinay M., Kelly P.A., Baixeras E. Growth hormone can act as a cytokine controlling survival and proliferation of immune cells: new insights into signaling pathways. Mol Cell Endocrinol 2002; 188: 1-7.Jeay S., Sonenshein G., Postel-Vinay M., Kelly P.A., Baixeras E. Growth hormone can act as a cytokine controlling survival and proliferation of immune cells: new insights into signaling pathways. Mol Cell Endocrinol 2002; 188: 1-7.Jeay S., Sonenshein G., Postel-Vinay M., Baixeras E. Growth hormone prevents apoptosis through activation of nuclear factor-kappaB in interleukin-3-dependent Ba/F3 cell line. Mol Endocrinol 2000; 14: 650-661.Jeay S., Sonenshein G., Postel-Vinay M., Baixeras E. Growth hormone prevents apoptosis through activation of nuclear factor-kappaB in interleukin-3-dependent Ba/F3 cell line. Mol Endocrinol 2000; 14: 650-661.Loeper S., Ezzat S. Acromegaly: re-thinking the cancer risk. Insulin-like growth factor I correlates with lean body mass in cystic fibrosis patients. Rev Endocrinol Metab Dis 2008; 9: 1: 41-58.Loeper S., Ezzat S. Acromegaly: re-thinking the cancer risk. Insulin-like growth factor I correlates with lean body mass in cystic fibrosis patients. Rev Endocrinol Metab Dis 2008; 9: 1: 41-58.Moller D.E., Flier J.S. Detection of an alteration in the insulin-reseptor gene in a patient with insulin resistance, acantosis nigricans and polycystic ovarian syndrome. N Engl J Med 1988; 319: 1526-1532.Moller D.E., Flier J.S. Detection of an alteration in the insulin-reseptor gene in a patient with insulin resistance, acantosis nigricans and polycystic ovarian syndrome. N Engl J Med 1988; 319: 1526-1532.Zimmet P., Boyko E.J., Collier G.R., De Courten M. Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. Ann N Y Acad Sci 1999; 892: 25-44.Zimmet P., Boyko E.J., Collier G.R., De Courten M. Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. Ann N Y Acad Sci 1999; 892: 25-44.Colao A., Pivolenello R., Aueriemma R., Galdiero M., Ferone D., Minuto F., Marzullo P., Lombardi G. The association of fasting insulin concentrations and colonic neoplasms in acromegaly: a colonoscopy-based study in 210 patients. J Clin Endocrinol Metab 2007; 92: 10: 3854-3860.Colao A., Pivolenello R., Aueriemma R., Galdiero M., Ferone D., Minuto F., Marzullo P., Lombardi G. The association of fasting insulin concentrations and colonic neoplasms in acromegaly: a colonoscopy-based study in 210 patients. J Clin Endocrinol Metab 2007; 92: 10: 3854-3860.Renehan A.G., Connell J.O., Halloran D.O., Shanahan F., Potten C., O'Dwyer S., Shalet S. Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications. Horm Metab Res 2003; 35: 11-12: 70-81.Renehan A.G., Connell J.O., Halloran D.O., Shanahan F., Potten C., O'Dwyer S., Shalet S. Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications. Horm Metab Res 2003; 35: 11-12: 70-81.Renehan A., Tyson M., Egger M., Heller R.F., Zwahlen M. Body mass index and incidence of cancer: a systematic review and metaanalysis of prospective observational studies. Lancet 2008; 371: 9612: 569-578.Renehan A., Tyson M., Egger M., Heller R.F., Zwahlen M. Body mass index and incidence of cancer: a systematic review and metaanalysis of prospective observational studies. Lancet 2008; 371: 9612: 569-578.Landreth K., Narayanan R., Dorshkind K. Insulin-like growth factor-I regulates pro-B cell differentiation. Blood 1992; 80: 5: 1207-1212.Landreth K., Narayanan R., Dorshkind K. Insulin-like growth factor-I regulates pro-B cell differentiation. Blood 1992; 80: 5: 1207-1212.Kelley K.W. From hormones to immunity: the physiology of immunology. Brain Behav Immun 2004; 18: 2: 95-113.Kelley K.W. From hormones to immunity: the physiology of immunology. Brain Behav Immun 2004; 18: 2: 95-113.Ergun-Longmire B., Mertens A., Mitby P., Qin J., Heller G., Shi W., Yasui Y., Robison L.L., Sklar C.A. Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab 2006; 91: 9: 3494-3498.Ergun-Longmire B., Mertens A., Mitby P., Qin J., Heller G., Shi W., Yasui Y., Robison L.L., Sklar C.A. Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab 2006; 91: 9: 3494-3498.Chan J.N., Stampfer M.J., Giovannucci E., Gann P.H., Ma J., Wilkinson P., Hennekens C.H., Pollak M. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998; 279: 563-566.Chan J.N., Stampfer M.J., Giovannucci E., Gann P.H., Ma J., Wilkinson P., Hennekens C.H., Pollak M. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998; 279: 563-566.De Mello-Coelho V., Gagnerault M., Souberbielle J., Strasburger C.J., Savino W., Dardenne M., Postel-Vinay M.C. Growth hormone and its receptor are expressed in human thymic cells. Endocrinol 1998; 139: 3837-3842.De Mello-Coelho V., Gagnerault M., Souberbielle J., Strasburger C.J., Savino W., Dardenne M., Postel-Vinay M.C. Growth hormone and its receptor are expressed in human thymic cells. Endocrinol 1998; 139: 3837-3842.Desbois-Mouthon C., Cadoret A., Blivet-Van Eggelpoel M.J., Bertrand F., Cherqui G., Perret C., Capeau J. Insulin and IGF-1 stimulate the beta-catenin pathway through two signalling cascades involving GSK-3beta inhibition and Ras activation. Oncogene 2001; 20: 2: 252-259.Desbois-Mouthon C., Cadoret A., Blivet-Van Eggelpoel M.J., Bertrand F., Cherqui G., Perret C., Capeau J. Insulin and IGF-1 stimulate the beta-catenin pathway through two signalling cascades involving GSK-3beta inhibition and Ras activation. Oncogene 2001; 20: 2: 252-259.Tseng Y.H., Kessler M.A., Schuler L.A. Regulation of cytokine expression by growth hormone and prolactin in bovine thymic stromal cells. Mol Cell Endocrinol 1997; 128: 117-127.Tseng Y.H., Kessler M.A., Schuler L.A. Regulation of cytokine expression by growth hormone and prolactin in bovine thymic stromal cells. Mol Cell Endocrinol 1997; 128: 117-127.Kooijman R., Coppens A., Hooghe-Peters E. IGF-I inhibits spontaneous apoptosis in human granulocytes. Endocrinol 2002; 143: 4: 1206-1212.Kooijman R., Coppens A., Hooghe-Peters E. IGF-I inhibits spontaneous apoptosis in human granulocytes. Endocrinol 2002; 143: 4: 1206-1212.Jeay S., Sonenshein G., Kelly P., Postel-Vinay M.C., Baixeras E. Growth hormone exerts antiapoptotic and proliferative effects through two different pathways involving nuclear factor-kappaB and phosphatidylinositol 3-kinase. Endocrinol 2001; 142: 1: 147-156.Jeay S., Sonenshein G., Kelly P., Postel-Vinay M.C., Baixeras E. Growth hormone exerts antiapoptotic and proliferative effects through two different pathways involving nuclear factor-kappaB and phosphatidylinositol 3-kinase. Endocrinol 2001; 142: 1: 147-156.Michaylira C.Z., Ramocki N.M., Simmons J.G., Tanner C.K., McNaughton K.K., Woosley J.T., Greenhalgh C.J., Lund P.K. Haplotype Insufficiency for Suppressor of Cytokine Signaling-2 Enhances Intestinal Growth and Promotes Polyp Formation in Growth Hormone-Transgenic Mice. Endocrinol 2006; 147: 4: 1632-1641.Michaylira C.Z., Ramocki N.M., Simmons J.G., Tanner C.K., McNaughton K.K., Woosley J.T., Greenhalgh C.J., Lund P.K. Haplotype Insufficiency for Suppressor of Cytokine Signaling-2 Enhances Intestinal Growth and Promotes Polyp Formation in Growth Hormone-Transgenic Mice. Endocrinol 2006; 147: 4: 1632-1641.Shimada T., Kojima K., Yoshiura K., Hiraishi H., Terano A. Characteristics of the peroxisome proliferator activated receptor gamma (PPAR) ligand induced apoptosis in colon cancer cells. Gut 2002; 50: 658-664.Shimada T., Kojima K., Yoshiura K., Hiraishi H., Terano A. Characteristics of the peroxisome proliferator activated receptor gamma (PPAR) ligand induced apoptosis in colon cancer cells. Gut 2002; 50: 658-664.

The authors declare that there are no conflicts of interest present.