Skip to main content
Log in

Plasticity of neuroendocrine and immune systems in early development

  • Developmental Biology
  • Published:
Biology Bulletin Aims and scope Submit manuscript

Abstract

This article provides an analysis of our own and published data on the reciprocal morphogenetic influence of the neuroendocrine and immune systems on their formation and function in mammals. It is substantiated that, in early ontogeny, neurohormones regulate the growth and differentiation of various tissues in the body, including the lymphoid tissue. Thymic peptides, in turn, affect the development of the hypothalamic-pituitary-adrenal and gonadal systems. Various adverse factors and changes in the physiological concentrations of hormones in the critical periods of development of these systems change their functions, and the plasticity of physiological systems in early ontogeny allows the body to adapt to new conditions. Disturbances in the interaction of the neuroendocrine and immune systems in the perinatal period induce a predisposition to various diseases in progeny.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alaniz, R.C., Thomas, S.A., Perez-Melgosa, M., et al., Dopamine beta-hydroxylase deficiency impairs cellular immunity, Proc. Natl. Acad. Sci. U.S.A., 1999, vol. 96, pp. 2274–2278.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Azad, N., LaPaglia, N., Agrawal, L., et al., The role of gonadectomy and testosterone replacement on thymic luteinizing hormone-releasing hormone production, J. Endocrinol., 1998, vol. 158, pp. 229–235.

    Article  PubMed  CAS  Google Scholar 

  • Barnard, A., Layton, D., Hince, M., et al., Impact of the neuroendocrine system on thymus and bone marrow function, Neuroimmunomodulation, 2008, vol. 15, pp. 7–18.

    PubMed  CAS  Google Scholar 

  • Boer, G.J., Quak, J., de Vries, M.C., and Heinsbroek, R.P., Mild sustained effects of neonatal vasopressin and oxytocin treatment on brain growth and behavior of the rat, Peptides, 1994, vol. 15, pp. 229–236.

    Article  PubMed  CAS  Google Scholar 

  • Bouchard, B., Ormandy, C.J., Di Santo, J.P., and Kelly, P.A., Immune system development and function in prolactin receptor-deficient mice, J. Immunol., 1999, vol. 163, pp. 576–582.

    PubMed  CAS  Google Scholar 

  • Van den Broek, H.H., Damoiseaux, J.G., De Baets, M.H., and Hupperts, R.M., The influence of sex hormones on cytokines in multiple sclerosis and experimental autoimmune encephalomyelitis: a review, Mult. Scler., 2005, vol. 11, pp. 349–359.

    Article  PubMed  Google Scholar 

  • Brown, O.A., Sosa, Y.E., Dardenne, M., et al., Growth hormone-releasing activity of thymulin on pituitary somatotropes is age dependent, Neuroendocrinology, 1999, vol. 69, pp. 20–27.

    Article  PubMed  CAS  Google Scholar 

  • De Bruijn, M.F., Ma, X., Robin, C., et al., Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta, Immunity, 2002, vol. 16, pp. 673–683.

    Article  PubMed  Google Scholar 

  • Cameron, N.M., Shahrokh, D., Del Corpo, A., et al., Epigenetic programming of phenotypic variations in reproductive strategies in the rat through maternal care, J. Neuroendocrinol., 2008, vol. 20, pp. 795–801.

    Article  PubMed  CAS  Google Scholar 

  • Carreras, E., Turner, S., Paharkova-Vatchkova, V., et al., Estradiol acts directly on bone marrow myeloid progenitors to differentially regulate GM-CSF or Flt3 ligand-mediated dendritic cell differentiation, J. Immunol., 2008, vol. 180, pp. 727–738.

    Article  PubMed  CAS  Google Scholar 

  • Chapman, J.C., Christian, J.J., Pawlikowski, M.A., et al., Female house mice develop a unique ovarian lesion in colonies that are at maximum population density, Proc. Soc. Exp. Biol. Med., 2000, vol. 225, pp. 80–90.

    Article  PubMed  CAS  Google Scholar 

  • Chapman, J.C., Min, S., Kunaporn, S., et al., The differential effect of injecting estradiol-17beta, testosterone, and hydrocortisone during the immune adaptive period on the fertility of female mice, Am. J. Reprod. Immunol., 2001, vol. 46, pp. 288–297.

    Article  PubMed  CAS  Google Scholar 

  • Chapman, J.C., Min, S.H., and Freeh, S.M., The estrogen-injected female mouse: new insight into the etiology of PCOS, Reprod. Biol. Endocrinol., 2009, vol. 18, pp. 7–47.

    Google Scholar 

  • Charmandari, E., Achermann, J.C., Carel, J.C., et al., Stress response and child health, Sci. Signal., 2012, vol. 5, no. 248, mr. 1.

    Google Scholar 

  • Coe, C.L. and Lubach, G.R., Prenatal influences on neuroimmune set points in infancy, Ann. N.Y. Acad. Sci., 2000, vol. 917, pp. 468–477.

    Article  PubMed  CAS  Google Scholar 

  • Cone, R.D., Anatomy and regulation of the central melanocortin system, Nat. Neurosci., 2005, vol. 8, pp. 571–578.

    Article  PubMed  CAS  Google Scholar 

  • Cross, R.J., Bryson, J.S., and Roszman, T.L., Immunologic disparity in the hypopituitary dwarf mouse, J. Immunol., 1992, vol. 148, pp. 1347–1352.

    PubMed  CAS  Google Scholar 

  • Csaba, G., Tekes, K., and Pállinger, E., Influence of perinatal stress on the hormone content in immune cells of adult rats: dominance of ACTH, Horm. Metab. Res., 2009, vol. 41, pp. 617–620.

    Article  PubMed  CAS  Google Scholar 

  • Dixit, V.D., Sridaran, R., Edmonsond, M.A., et al., Gonadotropin-releasing hormone attenuates pregnancy-associated thymic involution and modulates the expression of antiproliferative gene product prohibitin, Endocrinology, 2003, vol. 144, pp. 1496–1505.

    Article  PubMed  CAS  Google Scholar 

  • Dorshkind, K. and 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, vol. 21, pp. 292–312.

    PubMed  CAS  Google Scholar 

  • Fabris, N., Mocchegiani, E., and Provinciali, M., Pituitary-thyroid axis and immune system: a reciprocal neuroendocrine-immune interaction, Hormone Res., 1995, vol. 43, pp. 29–38.

    Article  PubMed  CAS  Google Scholar 

  • Farookhi, R., Wesolowski, E., Trasler, J.M., et al., Modulation by neonatal thymectomy of the reproductive axis in male and female rats during development, Biol. Reprod., 1988, vol. 38, pp. 91–99.

    Article  PubMed  CAS  Google Scholar 

  • Farooqi, I.S. and O’Rahilly, S., Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity, Nat. Clin. Pract. Endocrinol. Metab., 2008, vol. 4, pp. 569–577.

    Article  PubMed  CAS  Google Scholar 

  • Foster, M.P., Montecino-Rodriguez, E., and Dorshkind, K., Proliferation of bone marrow pro-B cells is dependent on stimulation by the pituitary/thyroid axis, J. Immunol., 1999, vol. 163, pp. 5883–5890.

    PubMed  CAS  Google Scholar 

  • Fowden, A.L. and Forhead, A.J., Endocrine mechanisms of intrauterine programming, Reproduction, 2004, vol. 127, pp. 515–526.

    Article  PubMed  CAS  Google Scholar 

  • Gaillard, R.C., Daneva, T., Hadid, R., et al., The hypothalamo-pituitary-adrenal axis of athymic Swiss nude mice. The implications of t lymphocytes in the ACTH release from immune cells, Ann. N.Y. Acad. Sci., 1998, vol. 840, pp. 480–490.

    Article  PubMed  CAS  Google Scholar 

  • García, L., Hinojosa, L., Domíngue, R., et al., Effects of injecting thymulin into the anterior or medial hypothalamus or the pituitary on induced ovulation in prepubertal mice, Neuroimmunomodulation, 2005, vol. 12, pp. 314–320.

    Article  PubMed  Google Scholar 

  • Gonzalez, B., Ratner, L.D., Di Giorgio, N.P., et al., Endogenously elevated androgens alter the developmental programming of the hypothalamic-pituitary axis in male mice, Mol. Cell. Endocrinol., 2011, vol. 332, pp. 78–87.

    Article  PubMed  CAS  Google Scholar 

  • Gorski, R.A., Sexual differentiation of the brain: a model for drug-induced alterations of the reproductive system, Environ Health Perspect., 1986, vol. 70, pp. 163–175.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Goya, R.G., Cónsole, G.M., Spinelli, O.M., et al., Glucocorticoid-induced apoptosis in lymphoid organs is associated with a delayed increase in circulating deoxyribonucleic acid, Apoptosis, 2003, vol. 8, pp. 171–177.

    Article  PubMed  CAS  Google Scholar 

  • Goya, R.G., Brown, O.A., Pléau, J.M., and Dardenne, M., Thymulin and the neuroendocrine system, Peptides, 2004, vol. 25, pp. 139–142.

    Article  PubMed  CAS  Google Scholar 

  • Goya, R.G., Reggiani, P.C., Vesenbeckh, S.M., et al., Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice, Am. J. Physiol. Endocrinol. Metab., 2007, vol. 293, pp. 182–187.

    Article  Google Scholar 

  • Grayson, B.E., Levasseur, P.R., Williams, S.M., et al., Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet, Endocrinology, 2010, vol. 15, pp. 1622–1632.

    Article  Google Scholar 

  • Hong, L., Colpan, A., and Peptan, I.A., Modulations of 17-beta estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells, Tissue Eng., 2006, vol. 12, pp. 2747–2753.

    Article  PubMed  CAS  Google Scholar 

  • Izvol’skaya, M.S., Sharova, V.S., and Zakharova, L.A., Mechanisms of hypothalamic-pituitary and immune system regulation: the role of gonadotropin-releasing hormone and immune mediators, Biol. Bull. (Moscow), 2010, vol. 37, no. 4, pp. 382–391.

    Article  Google Scholar 

  • Jacobson, J.D., Gonadotropin-releasing hormone and G proteins: potential roles in autoimmunity, Ann. N.Y. Acad. Sci., 2000, vol. 917, pp. 330–336.

    Google Scholar 

  • Jacobson, J.D. and Ansari, M.A., Immunomodulatory actions of gonadal steroids may be mediated by gonadotropin-releasing hormone, Endocrinology, 2004, vol. 145, pp. 330–336.

    Article  PubMed  CAS  Google Scholar 

  • Kelley, K.W., Weigent, D.A., and Kooijman, R., Protein hormones and immunity, Brain Behav. Immun., 2007, vol. 21, pp. 384–392.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Khegai, I.I., Gulyaeva, M.A., Popova, N.A., et al., Immune system in vasopressin-deficient rats during ontogeny, Byull. Eksp. Biol. Med., 2003, vol. 136, no. 5, pp. 448–450.

    Article  CAS  Google Scholar 

  • Koenig, R.J., Thyroid hormone receptor coactivators and corepressors, Thyroid, 1998, vol. 8, pp. 703–713.

    Article  PubMed  CAS  Google Scholar 

  • Kvetnoi, I.M., Yarilin, A.A., Polyakova, V.O., and Knyaz’kin, I.V., Neiroimmuno-endokrinologiya timusa (Thymus Neuroimmunoendocrinology), St. Petersburg: DEAN, 2005.

    Google Scholar 

  • Li, S., Creshaw, E.B., Rawson, E.J., et al., Dwarf locus mutants lacking three pituitary cell types result from mutations in the pou-domain gene pit-1, Nature, 1990, vol. 347, pp. 528–533.

    Article  PubMed  CAS  Google Scholar 

  • Mel’nikova, V.I., Afanas’eva, M.A., Voronova, S.N., and Zakharova, L.A., The effect of catecholamine deficit on the development of the immune system in rats, Dokl. Biol. Sci., 2012a, vol. 443, pp. 68–70.

    Article  Google Scholar 

  • Mel’nikova, V.I., Izvol’skaya, M.S., Voronova, S.N., and Zakharova, L.A., The role of serotonin in the immune system development and functioning during ontogenesis, Biol. Bull. (Moscow), 2012b, vol. 39, no. 3, pp. 237–243.

    Article  Google Scholar 

  • Montecino-Rodriguez, E., Clark, R.G., Powell-Braxton, L., and Dorshkind, K., Primary B cell development is impaired in mice with defects of the pituitary/thyroid axis, J. Immunol., 1997, vol. 159, pp. 2712–2719.

    PubMed  CAS  Google Scholar 

  • Morale, M.C., Batticane, N., and Bartoloni, G., Blocade of central and peripheral luteinizing hormone-releasing hormone (LHRH) receptors in neonatal rats with a potent LHRH-antagonist inhibits the morphofunctional development of the thymus and maturation of the cell-mediated and humoral immune responses, Endocrinology, 1991, vol. 128, pp. 1073–1085.

    Article  PubMed  CAS  Google Scholar 

  • Nagy, E. and Berczi, I., Immunodeficiency in hypophysectomized rats, Acta Endocrinol. (Copenh.), 1978, vol. 89, pp. 530–537.

    CAS  Google Scholar 

  • Nagy, E., Berczi, I., and Friesen, H.G., Regulation of immunity in rats by lactogenic and growth hormones, Acta Endocrinol. (Copenh.), 1983, vol. 102, pp. 351–357.

    CAS  Google Scholar 

  • Nicoll, C.S., Mayer, G.L., and Russell, S.M., Structural features of prolactins and growth hormones that can be related to their biological properties, Endocr. Rev., 1986, vol. 7, pp. 169–203.

    Article  PubMed  CAS  Google Scholar 

  • Olsen, N.J. and Kovacs, W.J., Gonadal steroids and immunity, Endocr. Rev., 1996, vol. 17, pp. 369–384.

    PubMed  CAS  Google Scholar 

  • Olsen, N.J. and Kovacs, W.J., Effects of androgens on T and B lymphocyte development, Immunol. Res., 2001, vol. 23, pp. 281–288.

    Article  PubMed  CAS  Google Scholar 

  • Provinciali, M. and Fabris, N., Models and mechanisms of neuroendocrine-immune interactions during ontogeny, Adv. Neuroimmunol., 1991, vol. 1, pp. 124–138.

    Article  CAS  Google Scholar 

  • Reyes, T.M. and Coe, C.L., Prenatal manipulations reduce the proinflammatory response to a cytokine challenge in juvenile monkeys, Brain Res., 1997, vol. 769, pp. 29–35.

    Article  PubMed  CAS  Google Scholar 

  • Roper, R.J., Ma, R.Z., Biggins, J.E., et al., Interacting quantitative trait loci control loss of peripheral tolerance and susceptibility to autoimmune ovarian dysgenesis after day 3 thymectomy in mice, J. Immunol., 2002, vol. 169, pp. 1640–1646.

    Article  PubMed  CAS  Google Scholar 

  • Sacedón, R., Vicente, A., Varas, A., et al., Role of glucocorticoids in early T-cell differentiation, Ann. N.Y. Acad. Sci., 2000, vol. 917, pp. 732–740.

    Article  PubMed  Google Scholar 

  • Safieh-Garabedian, B., Kanaan, S.A., Jabbur, S.J., et al., Cytokine-mediated or direct effects of thymulin on the nervous system as assessed by pain-related behavior, Neuroimmunomodulation, 1999, vol. 6, pp. 39–44.

    Article  PubMed  CAS  Google Scholar 

  • Sarasa, M. and Climent, S., Cardiac differentiation induced by dopamine in undifferentiated cells of early chick embryo, Dev. Biol., 1991, vol. 148, pp. 243–248.

    Article  PubMed  CAS  Google Scholar 

  • Savino, W., de Mello-Coelho, V., and Dardenne, M., Control of the thymic microenvironment by growth hormone/insulin-like growth factor-i mediated circuits, Neuroimmunomodulation, 1995, vol. 2, pp. 313–318.

    Article  PubMed  CAS  Google Scholar 

  • Sferruzzi-Perri, A.N., Owens, J.A., Pringle, K.G., and Roberts, C.T., The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth, J. Physiol., 2011, vol. 589, pp. 7–20.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Shulz, K.M., Molenda-Figueira, H.A., and Sisk, C.L., Back to the future: the organizational-activational hypothesis adapted to puberty and adolescence, Horm. Behav., 2009, vol. 55, pp. 597–604.

    Article  Google Scholar 

  • Slotkin, T.A., Zhang, J., McCook, E.C., et al., Glucocorticoid administration alters nuclear transcription factors in fetal rat brain: implications for the use of antenatal steroids, Brain Res. Dev. Brain Res., 1998, vol. 111, pp. 11–24.

    Article  PubMed  CAS  Google Scholar 

  • Staples, J.E., Gasiewicz, T.A., Fiore, N.C., et al., Estrogen receptor alpha is necessary in thymic development and estradiol-induced thymic alterations, J. Immunol., 1999, vol. 163, pp. 4168–4174.

    PubMed  CAS  Google Scholar 

  • Tanriverdi, F., Silveira, L.F., MacColl, G.S., and Bouloux, P.M., The hypothalamic-pituitary-gonadal axis: immune function and autoimmunity, J. Endocrinol., 2003, vol. 176, pp. 293–304.

    Article  PubMed  CAS  Google Scholar 

  • Toms, S.A., Hercbergs, A., Liu, J., et al., Thyroid hormone depletion inhibits astrocytoma proliferation via a p53-independent induction of p21 (WAF1/CIP1), Anticancer Res., 1998, vol. 18, pp. 289–293.

    PubMed  CAS  Google Scholar 

  • Zakharova, L.A. and Izvolskaia, M.S., Interactions between the reproductive and immune systems during ontogenesis: the role of GnRH, sex steroids and immunomediators, in Sex Steroids, Scott, M.K., Ed., Zagreb.: InTech, 2012, pp. 341–370.

    Google Scholar 

  • Zakharova, L.A., Malyukova, I.V., Adamskaya, E.I., et al., Luteinizing hormone-releasing hormone in thymus and hypothalamus of rat fetuses: suppressing effect of antagonist and of antibodies on concanavalin A-induced proliferation of thymocytes, Biochemistry (Moscow), 2000, vol. 65, no. 10, pp. 1135–1139.

    CAS  Google Scholar 

  • Zakharova, L.A., Karyagina, A.Yu., Popova, N.A., et al., Humoral immune response in ontogeny of the brattleboro rats with a hereditary defect of vasopressin synthesis, Dokl. Biol. Sci., 2001, vol. 376, pp. 70–71.

    Article  Google Scholar 

  • Zakharova, L., Ermilova, I.Y., Melnikova, V., et al., Hypothalamic control of the cell-mediated immunity and of the luteinizing hormone-releasing hormone level in thymus and peripheral blood of rat fetuses, Neuroimmunomodulation, 2005, vol. 12, pp. 85–91.

    Article  PubMed  CAS  Google Scholar 

  • Zakharova, L.A., Plasticity of neuroendocrine-immune interactions during ontogeny: role of perinatal programming in pathogenesis of inflammation and stress-related diseases in adults, in Recent Patents on Endocrine, Metabolic and Immune Drug Discovery, 2009, vol. 3, pp. 11–27.

    Article  CAS  Google Scholar 

  • Zala, S.M., Chan, B.K., Bilbo, S.D., et al., Genetic resistance to infection influences a male’s sexual attractiveness and modulation of testosterone, Brain Behav. Immun., 2008, vol. 22, pp. 381–387.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. A. Zakharova.

Additional information

Original Russian Text © L.A. Zakharova, 2014, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2014, No. 5, pp. 437–447.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zakharova, L.A. Plasticity of neuroendocrine and immune systems in early development. Biol Bull Russ Acad Sci 41, 395–404 (2014). https://doi.org/10.1134/S1062359014050148

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1062359014050148

Keywords

Navigation