Parte de libro

Renner, U.; Sapochnik, M.; Lucia, K.; Stalla, G.K.; Arzt, E."Intrahypophyseal immune-endocrine interactions: Endocrine integration of the inflammatory inputs" (2017) Endocrine Immunology. 48:37-47
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor


Endotoxin (lipopolysaccharide, LPS) of gram-negative bacteria has been recognized for more than 40 years as a modulator of anterior pituitary hormone production. The action of LPS was thought to be predominantly mediated through LPS-stimulated immune cell-derived cytokines, and is part of the concept of immune-endocrine crosstalk, which regulates bidirectional adaptive processes between the endocrine and immune systems during inflammatory or infectious processes. With the detection of innate immune system components in the normal and tumoral pituitary, including the Toll-like receptor 4, the target of LPS, it has become evident that LPS can directly modify the physiology and pathophysiology of the anterior pituitary. LPS-induced intrapituitary mechanisms involve the stimulation of intrapituitary cytokines, and also directly act on hormone synthesis, growth, and apoptosis of endocrine cells. This review focuses on the effects of LPS on pituitary physiology, its interaction with pro- and anti-inflammatory factors, and the molecular mechanisms involved in these processes. © 2017 S. Karger AG, Basel. All rights reserved.


Documento: Parte de libro
Título:Intrahypophyseal immune-endocrine interactions: Endocrine integration of the inflammatory inputs
Autor:Renner, U.; Sapochnik, M.; Lucia, K.; Stalla, G.K.; Arzt, E.
Filiación:Max Planck Institute of Psychiatry, Neuroendocrinology Group, Munich, Germany
Instituto de Investigacion en Biomedicina de Buenos Aires (IBioBA), CONICET, Partner Institute of the Max Planck Society, Germany
Departamento de Fisiologia y Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:lipopolysaccharide; animal; human; hypophysis; immunology; innate immunity; physiology; Animals; Humans; Immunity, Innate; Lipopolysaccharides; Pituitary Gland
Página de inicio:37
Página de fin:47
Título revista:Endocrine Immunology
Título revista abreviado:Endocr. Immunol.


  • Besedovsky, H.O., del Rey, A., Immune-neuro-endocrine interactions: facts and hypotheses (1996) Endocr Rev, 17, pp. 64-102
  • Chrousos, G.P., The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation (1995) N Engl J Med, 332, pp. 1351-1362
  • Akira, S., Takeda, K., Kaisho, T., Toll-like receptors: critical proteins linking innate and acquired immunity (2001) Nat Immunol, 2, pp. 675-680
  • Chen, K., Huang, J., Gong, W., Iribarren, P., Dunlop, N.M., Wang, J.M., Toll-like receptors in inflammation, infection and cancer (2007) Int Immunopharmacol, 7, pp. 1271-1285
  • Lohrer, P., Gloddek, J., Nagashima, A.C., Korali, Z., Hopfner, U., Pereda, M.P., Lipopolysaccharide directly stimulates the intrapituitary interleukin-6 production by folliculostellate cells via specific receptors and the p38alpha mitogen-activated protein kinase/ nuclear factor-kappaB pathway (2000) Endocrinology, 141, pp. 4457-4465
  • Tichomirowa, M., Theodoropoulou, M., Lohrer, P., Schaaf, L., Losa, M., Uhl, E., Bacterial endotoxin (lipopolysaccharide) stimulates interleukin-6 production and inhibits growth of pituitary tumour cells expressing the toll-like receptor 4 (2005) J Neuroendocrinol, 17, pp. 152-160
  • Iwasaki, Y., Taguchi, T., Nishiyama, M., Asai, M., Yoshida, M., Kambayashi, M., Lipopolysaccharide stimulates proopiomelanocortin gene expression in AtT20 corticotroph cells (2008) Endocr J, 55, pp. 285-290
  • Sabatino, M.E., Sosa Ldel, V., Petiti, J.P., Mukdsi, J.H., Mascanfroni, I.D., Pellizas, C.G., Functional toll-like receptor 4 expressed in lactotrophs mediates LPSinduced proliferation in experimental pituitary hyperplasia (2013) Exp Cell Res, 319, pp. 3020-3034
  • Correa-de-Santana, E., Fröhlich, B., Labeur, M., Paez-Pereda, M., Theodoropoulou, M., Monteserin, J.L., NOD2 receptors in adenopituitary folliculostellate cells: expression and function (2009) J Endocrinol, 203, pp. 111-122
  • Breuel, K.F., Kougias, P., Rice, P.J., Wei, D., de Ponti, K., Wang, J., Anterior pituitary cells express pattern recognition receptors for fungal glucans: implications for neuroendocrine immune involvement in response to fungal infections (2004) Neuroimmunomodulation, 11, pp. 1-9
  • Fauquier, T., Guerineau, N.C., McKinney, R.A., Bauer, K., Mollard, P., Folliculostellate cell network: a route for long-distance communication in the anterior pituitary (2001) Proc Natl Acad Sci U S A, 98, pp. 8891-8896
  • Renner, U., De Santana, E.C., Gerez, J., Intrapituitary expression and regulation of the gp130 cytokine interleukin-6 and its implication in pituitary physiology and pathophysiology (2009) Ann N Y Acad Sci, 1153, pp. 89-97
  • Horiguchi, K., Fujiwara, K., Yoshida, S., Higuchi, M., Tsukada, T., Kanno, N., Isolation of dendriticcell-like S100ß-positive cells in rat anterior pituitary gland (2014) Cell Tissue Res, 357, pp. 301-308
  • Glennon, E., Kaunzner, U.W., Gagnidze, K., McEwen, B.S., Bulloch, K., Pituitary dendritic cells communicate immune pathogenic signals (2015) Brain Behav Immun, 50, pp. 232-240
  • Renner, U., Gloddek, J., Pereda, M.P., Arzt, E., Stalla, G.K., Regulation and role of intrapituitary IL-6 production by folliculostellate cells (1998) Domest Anim Endocrinol, 15, pp. 353-362
  • Jovanovic, I., Ugrenovic, S., Ljubomirovic, M., Vasovic, L., Cukuranovic, R., Stefanovic, V., Folliculo-stellate cells-potential mediators of the inflammation-induced hyperactivity of the hypothalamic-pituitaryadrenal axis in healthy elderly individuals (2014) Med Hypotheses, 83, pp. 501-505
  • Gautron, L., Lafon, P., Tramu, G., Laye, S., In vivo activation of the interleukin-6 receptor/gp130 signaling pathway in pituitary corticotropes of lipopolysaccharide-treated rats (2003) Neuroendocrinology, 77, pp. 32-43
  • Gloddek, J., Lohrer, P., Stalla, J., Arzt, E., Stalla, G.K., Renner, U., The intrapituitary stimulatory effect of lipopolysaccharide on ACTH secretion is mediated by paracrine-acting IL-6 (2001) Exp Clin Endocrinol Diabetes, 109, pp. 410-415
  • Zaldivar, V., Magri, M.L., Zarate, S., Jaita, G., Eijo, G., Radl, D., Estradiol increases the expression of TNF-a and TNF receptor 1 in lactotropes (2011) Neuroendocrinology, 93, pp. 106-113
  • Pereira Suarez, A.L., Lopez-Rincon, G., Martinez Neri, P.A., Estrada-Chavez, C., Prolactin in inflammatory response (2015) Adv Exp Med Biol, 846, pp. 243-264
  • Tomaszewska-Zaremba, D., Herman, A., The role of immunological system in the regulation of gonadoliberin and gonadotropin secretion (2009) Reprod Biol, 9, pp. 11-23
  • Watanobe, H., Haykawa, Y., Hypothalamic interleukin-1ß and tumor necrosis factor-a, but not interleukin-6, mediate the endotoxin-induced suppression of the reproductive axis in rats (2003) Endocrinology, 144, pp. 4868-4875
  • Herman, A.P., Misztal, T., Romanowicz, K., Tomaszewska-Zaremba, D., Central injection of exogenous IL-1ß in the control activities of hypothalamic-pituitarygonadal axis in anestrous ewes (2012) Reprod Domest Anim, 47, pp. 44-52
  • MacEwan, D.J., Interactions between TNF and GnRH (2008) Neurochem Res, 33, pp. 678-682
  • Reynoso, R., Ponzo, O., Cardoso, N., Szwarcfarb, B., Carbone, S., Moguilevsky, J., Effect of bacterial lipopolysaccharide on the reproductive axis of prepubertal and peripubertal female rats. Ontogenic changes in the immune-neuroendocrine interactions (2008) Neuroimmunomodulation, 15, pp. 125-130
  • Friebe, A., Douglas, A.J., Solano, E., Blois, S.M., Hagen, E., Klapp, B.F., Neutralization of LPS or blockage of TLR4 signaling prevents stress-triggered fetal loss in murine pregnancy (2011) J Mol Med (Berl), 89, pp. 689-699
  • Mainardi, G.L., Saleri, R., Tamanini, C., Baratta, M., Effects of interleukin-1-beta, interleukin-6 and tumor necrosis factor-alpha, alone or in association with hexarelin or galanin, on growth hormone gene expression and growth hormone release from pig pituitary cells (2002) Horm Res, 58, pp. 180-186
  • Gong, F.Y., Deng, J.Y., Shi, Y.F., Stimulatory effect of interleukin-1beta on growth hormone gene expression and growth hormone release from rat GH3 cells (2005) Neuroendocrinology, 81, pp. 217-228
  • Daniel, J.A., Elsasser, T.H., Martinez, A., Steele, B., Whitlock, B.K., Sartin, J.L., Interleukin-1beta and tumor necrosis factor-alpha mediation of endotoxin action on growth hormone (2005) Am J Physiol Endocrinol Metab, 289, pp. E650-E657
  • Peeters, B., Boonen, E., Langouche, L., Van den Berghe, G., The HPA axis response to critical illness: new study results with diagnostic and therapeutic implications (2015) Mol Cell Endocrinol, 408, pp. 235-240
  • Kanczkowski, W., Sue, M., Zacharowski, K., Reincke, M., Bornstein, S.R., The role of adrenal gland microenvironment in the HPA axis function and dysfunction during sepsis (2015) Mol Cell Endocrinol, 408, pp. 241-248
  • Boonen, E., Vervenne, H., Meersseman, P., Andrew, R., Mortier, L., Declercq, P.E., Reduced cortisol metabolism during critical illness (2013) N Engl J Med, 368, pp. 1477-1488
  • Arzt, E., Buric, R., Stelzer, G., Stalla, J., Sauer, J., Renner, U., Interleukin involvement in anterior pituitary cell growth regulation: effects of IL-2 and IL-6 (1993) Endocrinology, 132, pp. 459-467
  • Eijo, G., Zarate, S., Jaita, G., Ferraris, J., Magri, M.L., Zaldivar, V., Radl, D., Seilicovich, A., Inhibition of nuclear factor-kappa B sensitises anterior pituitary cells to tumour necrosis factor-a-and lipopolysaccharide-induced apoptosis (2011) J Neuroendocrinol, 23, pp. 651-659
  • Gottardo, M.F., Jaita, G., Magri, M.L., Zarate, S., Moreno Ayala, M., Ferraris, J., Antiapoptotic factor humanin is expressed in normal and tumoral pituitary cells and protects them from TNF-a-induced apoptosis (2014) PLoS One, 9
  • Paoletta, A., Arnaldi, G., Papa, R., Boscaro, M., Tirabassi, G., Intrapituitary cytokines in Cushing's disease: do they play a role? (2011) Pituitary, 14, pp. 236-241
  • Newell-Price, J., Bertagna, X., Grossman, A.B., Nieman, L.K., Cushing's syndrome (2006) Lancet, 367, pp. 1605-1617
  • Sarlis, N.J., Chanock, S.J., Nieman, L.K., Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin (2000) J Clin Endocrinol Metab, 85, pp. 42-47
  • Honegger, J., Schlaffer, S., Menzel, C., Droste, M., Werner, S., Elbelt, U., Diagnosis of primary hypophysitis in Germany (2015) J Clin Endocrinol Metab, 100, pp. 3841-3849
  • Cuthbertson, D.J., Ritchie, D., Crooks, D., Main, G., Smith, C., Vora, J., Eljamel, M.S., Leese, G.P., Lymphocytic hypophysitis occurring simultaneously with a functioning pituitary adenoma (2008) Endocr J, 55, pp. 729-735
  • Powrie, J.K., Powell, M., Ayers, A.B., Lowy, C., Sönksen, P.H., Lymphocytic adenohypophysitis: magnetic resonance imaging features of two new cases and a review of the literature (1995) Clin Endocrinol (Oxf), 42, pp. 315-322
  • Honegger, J., Buchfelder, M., Schlaffer, S., Droste, M., Werner, S., Strasburger, C., Treatment of primary hypophysitis in Germany (2015) J Clin Endocrinol Metab, 100, pp. 3460-3469
  • Mehet, D.K., Philip, J., Solito, E., Buckingham, J.C., John, C.D., Evidence from in vitro and in vivo studies showing that nuclear factor-κB within the pituitary folliculostellate cells and corticotrophs regulates adrenocorticotrophic hormone secretion in experimental endotoxaemia (2012) J Neuroendocrinol, 24, pp. 862-873
  • Parnet, P., Pousset, F., Laye, S., NF kappa B activation in mouse pituitary: comparison of response to interleukin-1 beta and lipopolysaccharide (2003) J Neuroendocrinol, 15, pp. 304-314
  • Takayasu, S., Iwasaki, Y., Nigawara, T., Asai, M., Yoshida, M., Kageyama, K., Suda, T., Involvement of nuclear factor-kB and Nurr-1 in cytokine-induced transcription of proopiomelanocortin gene in AtT20 corticotroph cells (2010) Neuroimmunomodulation, 17, pp. 88-96
  • Kovalovsky, D., Paez Pereda, M., Labeur, M., Renner, U., Holsboer, F., Stalla, G.K., Arzt, E., Nur77 induction and activation are necessary for interleukin-1 stimulation of proopiomelanocortin in AtT-20 corticotrophs (2004) FEBS Lett, 563, pp. 229-233
  • Kovalovsky, D., Refojo, D., Liberman, A.C., Hochbaum, D., Pereda, M.P., Coso, O.A., Activation and induction of NUR77/NURR1 in corticotrophs by CRH/ cAMP: involvement of calcium, protein kinase A, and MAPK pathways (2002) Mol Endocrinol, 16, pp. 1638-1651
  • Pereda, M.P., Lohrer, P., Kovalovsky, D., Perez Castro, C., Goldberg, V., Losa, M., Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and POMC expression in human corticotroph pituitary adenomas (2000) Exp Clin Endocrinol Diabetes, 108, pp. 202-207
  • Kurotani, R., Yasuda, M., Oyama, K., Egashira, N., Sugaya, M., Teramoto, A., Expression of interleukin-6, interleukin-6 receptor (gp80), and the receptor's signal-transducing subunit (gp130) in human normal pituitary glands and pituitary adenomas (2001) Mod Pathol, 14, pp. 791-797
  • Fuchs, F., Damm, J., Gerstberger, R., Roth, J., Rummel, C., Activation of the inflammatory transcription factor nuclear factor interleukin-6 during inflammatory and psychological stress in the brain (2013) J Neuroinflammation, 10, p. 140
  • Silverman, M.N., Sternberg, E.M., Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction (2012) Ann N Y Acad Sci, 1261, pp. 55-63
  • Busillo, J.M., Cidlowski, J.A., The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore (2013) Trends Endocrinol Metab, 24, pp. 109-119
  • Uchoa, E.T., Aguilera, G., Herman, J.P., Fiedler, J.L., Deak, T., de Sousa, M.B., Novel aspects of glucocorticoid actions (2014) J Neuroendocrinol, 26, pp. 557-572
  • De Bosscher, K., Vanden Berghe, W., Haegeman, G., The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression (2003) Endocr Rev, 24, pp. 488-522
  • Refojo, D., Liberman, A.C., Giacomini, D., Carbia Nagashima, A., Graciarena, M., Echenique, C., Integrating systemic information at the molecular level: cross-talk between steroid receptors and cytokine signaling on different target cells (2003) Ann N Y Acad Sci, 992, pp. 196-204
  • Buckingham, J.C., John, C.D., Solito, E., Tierney, T., Flower, R.J., Christian, H., Annexin 1, glucocorticoids, and the neuroendocrine-immune interface (2006) Ann N Y Acad Sci, 1088, pp. 396-409
  • Brown, R., Imran, S.A., Wilkinson, M., Lipopolysaccharide (LPS) stimulates adipokine and socs3 gene expression in mouse brain and pituitary gland in vivo, and in N-1 hypothalamic neurons in vitro (2009) J Neuroimmunol, 209, pp. 96-103
  • Le Drean, Y., Mincheneau, N., Le Goff, P., Michel, D., Potentiation of glucocorticoid receptor transcriptional activity by sumoylation (2002) Endocrinology, 143, pp. 3482-3489
  • Holmstrom, S.R., Chupreta, S., So, A.Y., Iniguez-Lluhi, J.A., SUMO-mediated inhibition of glucocorticoid receptor synergistic activity depends on stable assembly at the promoter but not on DAXX (2008) Mol Endocrinol, 22, pp. 2061-2075
  • Druker, J., Liberman, A.C., Antunica-Noguerol, M., Gerez, J., Paez-Pereda, M., Rein, T., RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity (2013) Mol Cell Biol, 33, pp. 2116-2127
  • Wittebole, X., Castanares-Zapatero, D., Laterre, P.F., Toll-like receptor 4 modulation as a strategy to treat sepsis (2010) Mediators Inflamm, 2010, p. 568396


---------- APA ----------
Renner, U., Sapochnik, M., Lucia, K., Stalla, G.K. & Arzt, E. (2017) . Intrahypophyseal immune-endocrine interactions: Endocrine integration of the inflammatory inputs. Endocrine Immunology, 48, 37-47.
---------- CHICAGO ----------
Renner, U., Sapochnik, M., Lucia, K., Stalla, G.K., Arzt, E. "Intrahypophyseal immune-endocrine interactions: Endocrine integration of the inflammatory inputs" . Endocrine Immunology 48 (2017) : 37-47.
---------- MLA ----------
Renner, U., Sapochnik, M., Lucia, K., Stalla, G.K., Arzt, E. "Intrahypophyseal immune-endocrine interactions: Endocrine integration of the inflammatory inputs" . Endocrine Immunology, vol. 48, 2017, pp. 37-47.
---------- VANCOUVER ----------
Renner, U., Sapochnik, M., Lucia, K., Stalla, G.K., Arzt, E. Intrahypophyseal immune-endocrine interactions: Endocrine integration of the inflammatory inputs. Endocr. Immunol. 2017;48:37-47.