The thymus-neuroendocrine axis: Physiology, molecular biology, and therapeutic potential of the thymic peptide thymulin

Annals of the New York Academy of Sciences

Volumn 1153, Issue , 2009, Pages 98-106

  Reggiani, Paula C ^a   Morel, Gustavo R ^a   Cónsole, Gloria M ^a   Barbeito, Claudio G ^b   Rodriguez, Silvia S ^a   Brown, Oscar A ^a   Bellini, Maria Jose ^a   Pléau, Jean Marie ^c   Dardenne, Mireille ^c   Goya, Rodolfo G ^a,d  

^a FACULTAD DE CIENCIAS MÉDICAS   (Argentina)

^b UNIVERSIDAD NACIONAL DE LA PLATA   (Argentina)

^c CNRS   (France)

^d INSTITUTO DE INVESTIGACIONES BIOQUÍMICAS DE LA PLATA INIBIOLP   (Argentina)

Author keywords

Anti inflammatory; Artificial gene; Gene therapy; Hypophysiotropic activity; Neuroendocrine control; Ovarian dysgenesis; Thymulin

Indexed keywords

ADENOVIRUS VECTOR; THYMULIN; THYMUS HORMONE; ZINC;

ANALGESIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; BIOLOGICAL ACTIVITY; BRAIN; BRAIN CELL; CONFERENCE PAPER; EPITHELIUM CELL; FEMALE GENITAL SYSTEM; GENE THERAPY; HOMEOSTASIS; HUMAN; IMMUNE SYSTEM; LYMPHOCYTE DIFFERENTIATION; MOLECULAR BIOLOGY; NEUROENDOCRINE SYSTEM; NONHUMAN; PROTEIN EXPRESSION;

ANIMALIA; RATTUS;

EID: 60349099258     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2008.03964.x     Document Type: Conference Paper

References (70)

1. Goya, R.G. 1991. The immune-neuroendocrine homeostatic network and ageing. Gerontology 37 : 208 213.
2. Solomon, J.B. 1971. Ontogeny of defined immunity in mammals. In Foetal and Neonatal Immunology. Frontiers of Biology, Vol. 20. A. Neuberger & E.L. Tatum, Eds. : 234 306. American Elsevier Publishing Co. New York.
3. Jost, A. 1969. The extent of foetal and endocrine autonomy. In Foetal Autonomy. Ciba Foundation Symposium. G.E.W. Wolstenholme & M. O'Connor, Eds. : 79 94. Churchill. London.
4. Rebar, R.W., I.C. Morandini, G.F. Erickson, et al. 1981. The hormonal basis of reproductive defects in athymic mice. Endocrinology 108 : 120 126.
5. Besedovsky, H.O. & E. Sorkin. 1974. Thymus involvement in female sexual maturation. Nature 249 : 356 358.
6. Lintern-Moore, S. & E.M. Pantelouris. 1975. Ovarian development in athymic nude mice. I. The size and composition of the follicle population. Mech. Age. Dev. 4 : 385 390.
7. Michael, S.D., O. Taguchi & Y. Nishizuka. 1980. Effects of neonatal thymectomy on ovarian development and plasma LH, FSH, GH and PRL in the mouse. Biol. Reprod. 22 : 343 350.
8. Nishizuka, Y. & T. Sakakura. 1971. Ovarian dysgenesis induced by neonatal thymectomy in the mouse. Endocrinology 89 : 889 893.
9. Pierpaoli, W. & H.O. Besedovsky. 1975. Role of the thymus in programming of neuroendocrine functions. Clin. Exp. Immunol. 20 : 323 328.
10. Lintern-Moore, S. & E.M. Pantelouris. 1976. Ovarian development in athymic nude mice. III. The effect of PMSG and oestradiol upon the size and composition of the ovarian follicle population. Mech. Ageing. Dev. 5 : 33 38.
11. Goya, R.G., G.M. Cónsole, Y.E. Sosa, et al. 2001. Altered functional responses with preserved morphology of gonadotrophic cells in congenitally athymic mice. Brain Behav. Immun. 15 : 85 92.
12. Goya, R.G., Y.E. Sosa, G.M. Cónsole, et al. 1995. Altered thyrotropic and somatotropic responses to environmental challenges in congenitally athymic mice. Brain Behav. Immun. 9 : 79 86.
13. Goya, R.G., Y.E. Sosa, G.M. Cónsole, et al. 1996. Altered regulation of serum prolactin in nude mice. Med. Sci. Res. 24 : 279 280.
14. Daneva, T., E. Spinedi, R. Hadid, et al. 1995. Impaired hypothalamo-pituitary-adrenal axis function in swiss nude athymic mice. Neuroendocrinology 62 : 79 86.
15. Savino, W. & M. Dardenne. 2000. Neuroendocrine control of thymus physiology. Endocrine Rev. 21 : 412 443.
16. Bach, J.F. 1983. Thymulin (FTS-Zn). Clin. Immunol. Allergy 3 : 133 156.
17. Dardenne, M., M. Papiernik, J.F. Bach, et al. 1974. Studies on thymus products. III. Epithelial origin of the serum thymic factor. Immunology 27 : 299 304.
18. Gastinel, L.N., M. Dardenne, J.M. Pléau, et al. 1984. Studies on the zinc-binding site to the serum thymic factor. Biochim. Biophys. Acta 797 : 147 155.
19. Dardenne, M., B. Nabarra & P. Lefrancier. 1982. Contribution of zinc and other metals to the biological activity of serum thymic factor (FTS). Proc. Natl. Acad. Sci. USA 79 : 5370 5373.
20. Cung, M.T., M. Marraud, P. Lefrancier, et al. 1988. NMR study of a lymphocyte differentiating thymic factor. J. Biol. Chem. 263 : 5574 5580.
21. Savino, W., M. Dardenne & J.F. Bach. 1983. Thymic hormones containing cells. III. Evidence for a feed-back regulation of the secretion of the serum thymic factor (FTS) by thymic epithelial cells. Clin. Exp. Immunol. 52 : 7 12.
22. Cohen, S., S. Berrih, M. Dardenne, et al. 1986. Feed-back regulation of the secretion of a thymic hormone (thymulin) by human thymic epithelial cells in culture. Thymus 8 : 109 119.
23. Timsit, J., W. Savino, B. Safieh, et al. 1992. GH and IGF-I stimulate hormonal function and proliferation of thymic epithelial cells. J. Clin. Endocrinol. Metab. 75 : 183 188.
24. Ban, E., M.C. Gagnerault, H. Jammes, et al. 1991. Specific binding sites for growth hormone in cultured mouse thymic epithelial cells. Life Sci. 48 : 2141 2148.
25. Goff, B.L., J.A. Roth, L.H. Arp, et al. 1987. Growth hormone treatment stimulates thymulin production in aged dogs. Clin. Exp. Immunol. 68 : 580 587.
26. Goya, R.G., M.C. Gagnerault, M.C. Leite de Moraes, et al. 1992. In vivo effects of growth hormone on thymus function in aging mice. Brain Behav. Immun. 6 : 341 354.
27. Goya, R.G., M.C. Gagnerault, Y.E. Sosa, et al. 1993. Effects of growth hormone and thyroxine on thymulin secretion in aging rats. Neuroendocrinology 58 : 338 343.
28. Mocchegiani, E., P. Paolucci, A. Balsamo, et al. 1990. Influence of growth hormone on thymic endocrine activity in humans. Horm. Res. 33 : 7 14.
29. Dardenne, M., P.A. Kelly, J.F. Bach, et al. 1991. Identification and functional activity of Prl receptors in thymic epithelial cells. Proc. Natl. Acad. Sci. USA 88 : 9700 9704.
30. Dardenne, M., W. Savino, M.C. Gagnerault, et al. 1989. Neuroendocrine control of thymic hormonal production. I. Prolactin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells. Endocrinology 125 : 3 12.
31. Fabris, N. & E. Mocchegiani. 1985. Endocrine control of thymic serum factor production in young-adult and old mice. Cell. Immunol. 91 : 325 335.
32. Savino, W., B. Wolf, S. Aratan-Spire, et al. 1984. Thymic hormone containing cells. IV. Fluctuations in the thyroid hormone levels in vivo can modulate the secretion of thymulin by the epithelial cells of young mouse thymus. Clin. Exp. Immunol. 55 : 629 635.
33. Fabris, N., E. Mocchegiani, S. Mariotti, et al. 1986. Thyroid function modulates thymic endocrine activity. J. Clin. Endocrinol. Metab. 62 : 474 478.
34. Villa-Verde, D.M.S., V. Mello-Coelho, D.A. Farias de Oliveira, et al. 1993. Pleiotropic influence of triiodothyronine on thymus physiology. Endocrinology 133 : 867 875.
35. Mocchegiani, E., L. Amadio & N. Fabris. 1990. Neuroendocrine-thymus interactions. I. In vitro modulation of thymic factor secretion by thyroid hormones. J. Endocrinol. Invest. 13 : 139 147.
36. Dardenne, M., W. Savino, D. Duval, et al. 1986. Thymic hormone-containing cells. VII. Adrenals and gonads control the in vivo secretion of thymulin and its plasmatic inhibitor. J. Immunol. 136 : 1303 1308.
37. Savino, W., E. Bartoccioni, F. Homo-Delarche, et al. 1988. Thymic hormone containing cells. IX. Steroids in vitro modulate thymulin secretion by human and murine thymic epithelial cells. J. Steroid Biochem. 30 : 479 484.
38. Folch, H., G. Eller, M. Mena, et al. 1986. Neuroendocrine regulation of thymus hormones: hypothalamic dependence of FTS level. Cell. Immunol. 102 : 211 216.
39. Goya, R.G., M.C. Gagnerault & Y.E. Sosa. 1995. Reduced ability of pituitary extracts from old mice to stimulate thymulin secretion in vitro. Mech. Age. Dev. 83 : 143 154.
40. Zaidi, S.A., M.D. Kendall, B. Gillham, et al. 1988. The release of LH from pituitaries perifused with thymic extracts. Thymus 12 : 253 264.
41. Hadley, A.J., C.M. Rantle & J.C. Buckingham. 1997. Thymulin stimulates corticotrophin release and cyclic nucleotide formation in the rat anterior pituitary gland. Neuroimmunomodulation 4 : 62 69.
42. Hinojosa, L., L. García, R. Domínguez, et al. 2004. Effects of thymulin and GnRH on the release of gonadotropins by in vitro pituitary cells obtained from rats in each day of estrous cycle. Life Sci. 76 : 795 804.
43. Brown, O.A., Y.E. Sosa, F. Bolognani, et al. 1998. Thymulin stimulates prolactin and thyrotropin release in an age-related manner. Mech. Age. Dev. 104 : 249 262.
44. Brown, O.A., Y.E. Sosa, M. Dardenne, et al. 2000. Studies on the gonadotropin-releasing activity of thymulin: changes with age. J. Gerontol. (Biological Sciences) 55 : B170 176.
45. Hinojosa, L., R. Chavira, R. Dominguez, et al. 1999. Effects of thymulin on spontaneous puberty and gonadotrophin-induced ovulation in prepubertal normal and hypothymic mice. J. Endocrinol. 163 : 255 260.
46. García, L., L. Hinojosa, R. Domínguez, et al. 2000. Effects of infantile thymectomy on ovarian functions and gonadotrophin-induced ovulation in prepubertal mice. Role of thymulin. J. Endocrinol. 166 : 381 387.
47. García, L., L. Hinojosa, R. Domínguez, et al. 2005. Effects of injecting thymulin into the anterior or medial hypothalamus or the pituitary on induced ovulation in prepubertal mice. Neuroimmunomodulation 12 : 314 320.
48. Wise, T. 1998. In vitro and in vivo effects of thymulin on rat testicular steroid synthesis. J. Steroid. Biochem. Mol. Biol. 66 : 129 135.
49. Camihort, G., G. Luna, S. Vesenbeckh, et al. 2006. Morphometric assessment of the impact of serum thymulin immunoneutralization on pituitary cell populations in peripubertal mice. Cells Tiss. Organs 184 : 23 30.
50. Goya, R.G., P.C. Reggiani, S.M. Vesenbeckh, et al. 2007. Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice. Am. J. Physiol.-Endocrinol. Metab. 293 : E182 E187.
51. Goya, R.G., G.M. Cónsole, C.B. Hereñú, et al. 2002. Thymus and aging: Potential of gene therapy for restoration of endocrine thymic function in thymus-deficient animal models. Gerontology 48 : 325 328.
52. Calenda, A., A. Cordonnier, F. Lederer, et al. 1988. Production of biologically active thymulin in Escherichia coli through expression of a chemically synthesized gene. Biotechnol. Lett. 10 : 155 160.
53. Reggiani, P.C., C.B. Hereñú, O.J. Rimoldi, et al. 2006. Gene therapy for long-term restoration of circulating thymulin in thymectomized mice and rats. Gene Ther. 13 : 1214 1221.
54. Morel, G.R., O.A. Brown, P.C. Reggiani, et al. 2006. Peripheral and mesencephalic transfer of a synthetic gene for the thymic peptide thymulin. Brain Res. Bull. 69 : 647 651.
55. Safieh-Garabedian, B., M. Dardenne, J.-M. Pleau, et al. 2002. Potent analgesic and anti-inflammatory actions of a novel thymulin-related peptide in the rat. Br. J. Pharmacol. 136 : 947 955.
56. Safieh-Garabedian, B., C.I. Ochoa-Chaar, S. Poole, et al. 2003. Thymulin reverses inflammatory hyperalgesia and modulates the increased concentration of proinflammatory cytokines induced by i.c.v. endotoxin injection. Neuroscience 121 : 865 873.
57. Dardenne, M., N. Saade & B. Safieh-Garabedian. 2006. Role of thymulin or its analogue as a new analgesic molecule. Ann. N. Y. Acad. Sci. 1088 : 153 63.
58. Stone, D., W. Xiong, J.C. Williams, et al. 2003. Adenovirus expression of IL-1 and NF-kappaB inhibitors does not inhibit acute adenoviral induced brain inflammation, but delays immune system-mediated elimination of transgene expression. Mol. Ther. 8 : 400 411.
59. Reggiani, P.C., C.G. Barbeito, M.A. Flamini, et al. 2008. Neonatal thymulin gene therapy prevents the characteristic ovarian atrophy of adult nude mice (Abstract); Presented at the Seventh Meeting of the International Society for Neuroimmunomodulation. Rio de Janeiro, Brazil, 19-23 April.
60. Zeidler, A., C. Tosco, D. Kumar, et al. 1982. Spontaneous hyperglycemia and impaired glucose tolerance in athymic nude BALB/c mice. Diabetes 31 : 821 825.
61. Zeidler, A., D. Kumar, C. Johnson, et al. 1984. Development of a diabetes-like syndrome in an athymic nude Balb/c mouse colony. Exp. Cell. Biol. 52 : 145 149.
62. Zeidler, A., N.S. Shargill & T.M. Chan. 1991. Peripheral insulin insensitivity in the hyperglycemic athymic nude mouse: similarity to noninsulin-dependent diabetes mellitus. Proc. Soc. Exp. Biol. Med. 196 : 457 460.
63. Zeidler, A., S. Arbuckle, E. Mahan, et al. 1989. Assessment of pancreatic islet- cell population in the hyperglycemic athymic nude mouse: immunohistochemical, ultrastructural, and hormonal studies. Pancreas 4 : 153 160.
64. Velkov, Z., M. Zafirova, Z. Kemileva, et al. 1990. Time course changes in blood glucose and insulin levels of thymectomized rats. Acta Physiol. Pharmacol. Bulg. 16 : 64 67.
65. Mondola, P., L. Coscia Porrazzi & C. Falconi. 1979. Cholesterol and triglycerides of a liver after administration of a chromatographic fraction of thymus: variations in tissue and blood. Horm. Metab. Res. 11 : 503 505.
66. Mondola, P., M. Santillo, F. Santangelo, et al. 1992. Effects of a new calf thymus protein on 3-hydroxy-3-methyl-glutarylCoA reductase activity in rat (rattus bubalus) hepatocyte cells (BRL-3A). Comp. Biochem. Physiol. 103B : 431 434.
67. Mondola, P., M. Santillo, I. Tedesco, et al. 1989. Thymus fraction (FIII) effect on cholesterol metabolism: modulation of the low density lipoprotein receptor pathway. Int. J. Biochem. 21 : 627 630.
68. García-Bravo, M.M., M.P. Polo, P.C. Reggiani, et al. 2006. Partial prevention of hepatic lipid alterations in nude mice by neonatal thymulin gene therapy. Lipids 41 : 753 757.
69. Bach, J.F., M. Dardenne & A.L. Goldstein. 1984. Clinical aspects of thymulin (FTS). In Thymic Hormones and Lymphokines. Basic Chemistry and Clinical Applications. A.L. Goldstein, Ed. : 593 600. Plenum Press. New York.
70. Sztein, M.B. & A.L. Goldstein. 1986. Thymic hormones - a clinical update. Springer Sem. Immunopathol. 9 : 1 18.