Castro, C.P.; Peñalva, R.; Pereda, M.P.; Renner, U.; Reul, J.M.H.M.; Stalla, G.K.; Holsboer, F.; Arzt, E. "Early activation of thyrotropin-releasing-hormone and prolactin plays a critical role during a T cell-dependent immune response" (1999) Endocrinology. 140(2):690-697
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Functional interaction between the immune and neuroendocrine systems is mediated by humoral mediators, neurotransmitters, and cytokines, including TRH and PRL. We examined the role of neuroendocrine changes, particularly TRH and PRL, during the T cell-dependent immune response. After immunization of rats with sheep red blood cells (SRBC, a T cell-dependent antigen), an increase of hypothalamic TRH messenger RNA (mRNA) was observed at 4-24 h post immunization, in contrast to the decrease observed after treatment with lipopolysaccharide (LPS). During the above period, with SRBC, there was an increase in pituitary TRH receptor mRNA and plasma PRL levels but no changes in TSH and GH. Also, in contrast to the early corticosterone peak induced by LPS, the activation of the hypothalamic-pituitary-adrenocortical suppressive response appears in a late phase, 5-7 days after SRBC. Intracerebroventricular injection of antisense oligonucleotide complementary to rat TRH mRNA in conscious freely-moving rats immunized with SRBC resulted in a significant inhibition of specific antibody production and a concomitant inability to produce the peak in plasma PRL levels. These studies demonstrate, for the first time, that the T cell-dependent immune response is critically dependent on the early activation of TRH and PRL and that the neuroendocrine changes occurring during it are profoundly different from those occurring during the T cell-independent and inflammatory responses (LPS model).


Documento: Artículo
Título:Early activation of thyrotropin-releasing-hormone and prolactin plays a critical role during a T cell-dependent immune response
Autor:Castro, C.P.; Peñalva, R.; Pereda, M.P.; Renner, U.; Reul, J.M.H.M.; Stalla, G.K.; Holsboer, F.; Arzt, E.
Filiación:Max-Planck Institute of Psychiatry, Clinical Institute, Kraepelinstr, 2-10, 80804 Munich, Germany
Lab. de Fisiologia y Biologia Molec., Department de Bioloǵa, Fac. Ciencias Exactas y Naturales, Ciudad Universitaria-Pabellon II, 1428 Buenos Aires, Argentina
Palabras clave:prolactin; protirelin; animal tissue; article; cellular immunity; immune response; male; nonhuman; priority journal; prolactin release; rat; sheep; T lymphocyte; thyrotropin release
Página de inicio:690
Página de fin:697
Título revista:Endocrinology
Título revista abreviado:Endocrinology
CAS:prolactin, 12585-34-1, 50647-00-2, 9002-62-4; protirelin, 24305-27-9


  • Besedovsky, H., Del Rey, A., Immune-neuro-endocrine interactions: Facts and hypotheses (1996) Endocr Rev, 17, pp. 64-102
  • Ader, R., Felten, D., Cohen, N., Interactions between the brain and the the immune system (1990) Annu Rev Pharmacol Toxicol, 30, pp. 561-602
  • Besedovsky, H., Sorkin, E., Kelier, M., Muller, J., Changes in blood hormone levels during the immune response (1975) Proc Soc Exp Med, 150, pp. 466-502
  • Besedovsky, H., Del Rey, A., Sorkin, E., Da Prada, M., Burri, R., Honegger, C., The immune response evokes changes in brain noradrenergic neurons (1983) Science, 221, pp. 564-565
  • Toni, R., Jackson, I.M., Lechan, R.M., Thyrotropin-releasing-hormone-immunoreactive inervation of thyrotropin-releasing-hormone-tuberoinfundibular neurons in rat hypothalamus: Anatomical basis to suggest ultrashort feedback regulation (1990) Neuroendocrinology, 52, pp. 422-428
  • Masuda, M., Kanai, S., Miyasaka, K., Central somatostatin prevents vagal efferent nerve excitation produced by TRH but not by 2-deoxy-D-glucose (1997) Am J Physiol, 272, pp. G351-G356
  • Macleod, R.M., Lehmeyer, J.E., Studies on the mechanism of the dopaminemediated inhibition of prolactin secretion (1974) Endocrinology, 94, pp. 1077-1085
  • Comsa, J., Leonhardt, H., Schwarz, J.A., Influence of the thymus-cortico-tropin-growth hormone interaction on the rejection of skin allografts in the rat (1975) Ann NY Acad Sci, 249, pp. 387-401
  • Prentice, E.D., Lipscomb, H., Metcalf, W.K., Sharp, J.G., Effects of hypophysectomy on DNCB-induced contact sensitivity in rats (1976) Scand J Immunol, 5, pp. 955-961
  • Cross, R.J., Markesbery, W.R., Brooks, W.H., Roszman, T.L., Hypothalamicimmune interactions: Neuromodulation of natural killer activity by lesioning of the anterior hypothalamus (1984) Immunology, 51, pp. 399-405
  • Berczi, I., Nagy, E., Kovacs, K., Horvath, E., Regulation of humoral immunity in rats by pituitary hormones (1981) Acta Endocrinol (Copenh), 98, pp. 506-513
  • Nagy, E., Berczi, I., Wren, G.E., Asa, S.L., Kovacs, K., Immunomodulation by bromocriptine (1983) Immunopharmacology, 6, pp. 231-243
  • Hartmann, D.P., Holaway, J.W., Bernton, E.W., Inhibition of lymphocyte proliferation by antibodies to prolactine (1989) FASEB J, 3, pp. 2194-2202
  • Clevenger, C.V., Russell, D.H., Appasamy, P.M., Prystowsky, M.B., Regulation of interleukin-2 driven T-lymphocyte proliferation by prolactin (1990) Proc Natl Acad Sci USA, 87, pp. 6460-6464
  • Clevenger, C., Altmann, S.W., Prystowsky, M.B., Requirement of nuclear prolactin for interleukin-2-stimulated proliferation of T-lymphocytes (1991) Science, 253, pp. 77-79
  • Pelligrini, I., Lebrun, J.J., Ali, S., Kelly, P.A., Expression of prolactin and its receptor in human lymphoid cells (1992) Mol Endocrinol, 6, pp. 1023-1031
  • Murkherjee, P., Mastro, A.M., Hymer, W.C., Prolactine induction of interleukin-2 receptors on rat splenic lymphocytes (1990) Endocrinology, 126, pp. 88-93
  • Raiden, S., Polack, E., Nahmod, V., Labeur, M., Holsboer, F., Arzt, E., TRH receptor on immune cells: In vitro and in vivo stimulation of human lymphocyte and rat splenocyte DNA synthesis by TRH (1995) J Clin Immunol, 15, pp. 242-249
  • Kruger, T.E., Smith, L.R., Harbour, D.V., Blalock, J.E., Thyrotropin: An endogenous regulator of the in vitro immune response (1989) J Immunol, 142, pp. 744-747
  • Komorowski, J., Stepien, H., Pawlikowski, M., Increased interleukin-2 levels during standard TRH test in man (1994) Neuropeptides, 27, pp. 151-156
  • Pawlikowski, M., Zerek-Melén, G., Winczyk, K., Thyroliberin (TRH) increases thymus cell proliferation in rats (1992) Neuropeptides, 23, pp. 199-202
  • Reul, J.M.H.M., Stec, I., Wiegers, G.J., Labeur, M.S., Linthorst, A.C.E., Arzt, E., Holsboer, F., Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in the adult rats (1994) J Clin Invest, 93, pp. 2600-2607
  • Skutella, T., Criswell, H., Moy, S., Probst, J.C., Breese, G.R., Jirikowski, G.F., Holsboer, F., Corticotropin-releasing-hormone (CRH) antisense oligodeoxinucleotide induces anxiolitic effects in rat (1994) Neuroreport, 5, pp. 2181-2185
  • Paxinos, G., Watson, C., (1986) The Rat Brain in Stereotaxic Coordinates, , Academic Press, Sydney, Australia, figure 16
  • Lechan, R.M., Wu, P., Jackson, I.M.D., Wolf, H., Cooperman, S., Mandel, G., Goodman, R.H., Thyrotropin-releasing hormone precursor: Characterization in rat brain (1986) Science, 231, pp. 159-161
  • Garcia, S.I., Porto, P.I., Alvarez, A.L., Shaurli, D., Fienkelman, S., Pirola, C.J., Central overexpression of the TRH precursor gene induced hypertension in rats: Antisense reversal (1997) Hypertension, 30, pp. 759-766
  • Labeur, M., Arzt, E., Wiegers, G.J., Holsboer, F., Reul, J.M.H.M., Long-term intracerebroventricular corticotropin-releasing hormone administration induces distinct changes in rat splenocyte activation and cytokine expression (1995) Endocrinology, 136, pp. 2678-2688
  • Arzt, E., Stelzer, G., Renner, U., Lange, M., Müller, O.A., Stalla, G.K., Interleukin-2 and interleukin-2 receptor expression in human corticotrophin adenoma and murine pituitary cell cultures (1992) J Clin Invest, 90, pp. 1944-1951
  • Tsagarakis, S., Holly, J.M.P., Rees, L.H., Besser, G.M., Grossman, A., Acetylcholine and norepinephrine stimulate the release of corticotropin-releasing factor-41 from the rat hypothalamus in vitro (1988) Endocrinology, 123, pp. 1962-1969
  • Arzt, E., Sauer, J., Pollmacher, T., Labeur, M., Holsboer, F., Reul, J.M.H.M., Stalla, G.K., Glucocorticoids suppress interleukin-1 receptor antagonist synthesis following induction by endotoxin (1994) Endocrinology, 134, pp. 672-677
  • Straub, R.E., Frech, G.C., Joho, R.H., Gershengorn, M.C., Expression cloning of a cDNA encoding the mouse pituitary thyrotropin-releasing hormone receptor (1990) Proc Natl Acad Sci USA, 87, pp. 9514-9518
  • Kakusca, I., Romero, L., Clark, B., Rondeel, J., Qi, Y., Alex, S., Emerson, C., Lechan, R., Suppression of thyrotropin-releasing hormone gene expression by interleukin-1β in the rat: Implications for nonthyroidal illness (1994) Neuroendocrinology, 59, pp. 129-137
  • Wagner, R.W., Gene inhibition using antisense oligodeoxynucleotides (1994) Nature, 372, pp. 333-335
  • Besedovsky, H.O., Del Rey, A., Schardt, M., Sorkin, E., Normann, S., Baumann, J., Girard, J., Changes in plasma hormone profiles after tumor transplantation into syngeneic and allogeneic rats (1985) Int J Cancer, 36, pp. 209-216
  • Bernton, E., Beach, J.E., Holaday, J.W., Smallridge, R.C., Fein, H.G., Release of multiple hormones by a direct action of interleukin-1 on pituitary cells (1987) Science, 238, pp. 519-521
  • Arzt, E., Buric, R., Stelzer, G., Stalla, J., Sauer, J., Renner, U., Stalla, G.K., Interleukin involvement in anterior pituitary cell growth regulation: Effects of IL-2 and IL-6 (1993) Endocrinology, 132, pp. 459-467
  • Karanth, S., McCann, M.S., Anterior pituitary hormone control by interleukin-2 (1991) Proc Natl Acad Sci USA, 88, pp. 2961-2965
  • Karanth, S., McCann, M.S., Influence of dopamine on the altered release of prolactine, luteinizing hormone and follicle stimulating hormone induced by interleukin-2 in vitro (1992) Neuroendocrinology, 56, pp. 871-880
  • Felten, D.L., Felten, S.Y., Carlson, S.L., Olschowka, J.A., Livnat, S., Noradrenergic and peptidergic innervation of lymphoid tissue (1985) J Immunol, 135, pp. 755s-765s
  • MacNeil, B.J., Jansen, A.H., Greenberg, A.H., Nance, D.M., Activation and selectivity of splenic sympathetic nerve electrical activity response to bacterial endotoxin (1996) Am J Physiol, 270, pp. R264-R270
  • Gardier, A.M., Kachaner, S., Shaghaghi, E.K., Blot, C., Bohuon, C., Jacquot, C., Pallardy, M.J., Effects of primary immune response to T-cell-dependent antigen on serotonin metabolism in frontal cortex: In vivo microdialysis study in freely moving Fischer 344 rat (1994) Brain Res, 645, pp. 150-156
  • Merrill, J., Macroglia: Neural cells responsive to lymphokines and growth factors (1987) Immunol Today, 8, pp. 146-150
  • Hickey, W.F., Hsu, B.L., Kimura, H., T-lymphocyte entry into the central nervous system (1991) J Neurosci Res, 28, pp. 254-260
  • Snyder, P.J., Jacobs, L.S., Rabello, M.M., Sterling, F.H., Shore, R.N., Utiger, R.D., Daughaday, M.D., Diagnostic value of thyrotrophin-releasing hormone in pituitary and hypothalamic diseases (1974) Ann Intern Med, 81, pp. 751-757
  • Klindt, J., Davis, S.L., Ohlson, D.L., Plasma concentration of thyrotropin-releasing hormone, thyrotropin, prolactin, and growth hormone during five-day osmotic pump infusion of thyrotropin of thyrotropin-releasing hormone (1979) Endocrinology, 104, pp. 45-49
  • Hoang-Vu, C., Leitolf, H., Brabant, G., Continuous vs. pulsatile adminis-tration of thyrotropin-releasing hormone (TRH) in the model of the chronically cannulated rat: Long-term effects on thyroid function (1996) Exp Clin Endocrinol Diabetes, 104, pp. 51-54
  • Fabris, N., Mocchegiani, E., Provincial, M., Pituitary-thyroid axis and im-mune system: A reciprocal neuroendocrine-immune interaction (1995) Horm Res, 43, pp. 29-38
  • Silva, J.D., Nunes, M.T., Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats (1996) Braz J Med Biol Res, 29, pp. 677-683
  • Stenzel-Poore, M., Vale, W.W., Rivier, C., Relationship between antigen-induced immune stimulation and activation of the hypothalamic-pituitary-adrenal axis in the rat (1993) Endocrinology, 132, pp. 1313-1318
  • Redeï, E., Hilderbrand, H., Aird, F., Corticotropin release inhibiting factor is encoded within prepro-TRH (1995) Endocrinology, 136, pp. 1813-1816
  • Redei, E., Hilderbrand, H., Aird, F., Corticotropin release-inhibiting factor is preprothyrotropin-releasing hormone-(178-199) (1995) Endocrinology, 136, pp. 3557-3563
  • Rittenhouse, P.A., Redei, E., Thyroxine administration prevents streptococcal cell wall-induced inflammatory responses (1997) Endocrinology, 138, pp. 1434-1439


---------- APA ----------
Castro, C.P., Peñalva, R., Pereda, M.P., Renner, U., Reul, J.M.H.M., Stalla, G.K., Holsboer, F.,..., Arzt, E. (1999) . Early activation of thyrotropin-releasing-hormone and prolactin plays a critical role during a T cell-dependent immune response. Endocrinology, 140(2), 690-697.
---------- CHICAGO ----------
Castro, C.P., Peñalva, R., Pereda, M.P., Renner, U., Reul, J.M.H.M., Stalla, G.K., et al. "Early activation of thyrotropin-releasing-hormone and prolactin plays a critical role during a T cell-dependent immune response" . Endocrinology 140, no. 2 (1999) : 690-697.
---------- MLA ----------
Castro, C.P., Peñalva, R., Pereda, M.P., Renner, U., Reul, J.M.H.M., Stalla, G.K., et al. "Early activation of thyrotropin-releasing-hormone and prolactin plays a critical role during a T cell-dependent immune response" . Endocrinology, vol. 140, no. 2, 1999, pp. 690-697.
---------- VANCOUVER ----------
Castro, C.P., Peñalva, R., Pereda, M.P., Renner, U., Reul, J.M.H.M., Stalla, G.K., et al. Early activation of thyrotropin-releasing-hormone and prolactin plays a critical role during a T cell-dependent immune response. Endocrinology. 1999;140(2):690-697.