Artículo

García-Tornadú, I.; Díaz-Torga, G.; Risso, G.S.; Silveyra, P.; Cataldi, N.; Ramirez, M.C.; Low, M.J.; Libertun, C.; Becu-Villalobos, D. "Hypothalamic orexin, OX1, αMSH, NPY and MCRs expression in dopaminergic D2R knockout mice" (2009) Neuropeptides. 43(4):267-274
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

In 5-month-old male and female dopamine receptor 2 (D2R) knockout mice food intake per animal was unaltered while food per g BW was increased. We wished to evaluate the effect of D2R disruption on different components of energy balance and food intake regulation. We determined hypothalamic orexin precursor (PPO) expression, its receptor OX1, serum leptin levels, hypothalamic leptin receptor (OBR), circulating and pituitary α MSH levels, as well as central MC3 and MC4 receptors and NPY mRNA in wildtype and D2R knockout mice (KO). Loss of D2R caused a marked increase in serum prolactin levels, to higher levels in females compared to male KO mice. On the other hand, it produced a female-specific increase in circulating αMSH, and hypothalamic αMSH content, while neurointermediate αMSH content was decreased in both sexes. No differences were found in hypothalamic NPY, MC3R or MC4R concentration. Hypothalamic PPO mRNA expression was significantly decreased only in female KOs, while OX1 mRNA was not different between genotypes. Serum leptin levels were also similar in both genotypes. Our results show that in female and not in male mice disruption of the D2R produces two potentially anorexigenic events: an increase in serum and hypothalamic αMSH, and a decrease in hypothalamic orexin expression. Very high prolactin levels, which are orexigenic, probably counterbalance these effects, so that food intake is slightly altered. In males, on the other hand, hypothalamic PPO, and serum or hypothalamic αMSH are not modified, and increased prolactin levels may account for increased food intake per g BW. These results suggest a sexually dimorphic participation of the D2R in food intake regulation. © 2009 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Hypothalamic orexin, OX1, αMSH, NPY and MCRs expression in dopaminergic D2R knockout mice
Autor:García-Tornadú, I.; Díaz-Torga, G.; Risso, G.S.; Silveyra, P.; Cataldi, N.; Ramirez, M.C.; Low, M.J.; Libertun, C.; Becu-Villalobos, D.
Filiación:Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, V. Obligado 2490, 1428 Buenos Aires, Argentina
Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, United States
Palabras clave:Dopamine; Leptin; MC3; MC4; MSH; Orexin; Prolactin; alpha intermedin; dopamine 2 receptor; leptin; leptin receptor; melanocortin 3 receptor; melanocortin 4 receptor; melanocortin receptor; messenger RNA; neuropeptide Y; orexin; orexin 1 receptor; prolactin; animal cell; animal experiment; animal tissue; anorexia; article; body weight; controlled study; energy balance; feeding behavior; female; food intake; gene disruption; genotype; hypothalamus; knockout mouse; male; mouse; newborn; nonhuman; priority journal; protein expression; sex difference; wild type; alpha-MSH; Animals; Eating; Energy Metabolism; Female; Hypothalamus; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Knockout; Neuropeptide Y; Neuropeptides; Protein Precursors; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Receptors, Dopamine D2; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Animalia; Mus
Año:2009
Volumen:43
Número:4
Página de inicio:267
Página de fin:274
DOI: http://dx.doi.org/10.1016/j.npep.2009.06.002
Título revista:Neuropeptides
Título revista abreviado:Neuropeptides
ISSN:01434179
CODEN:NRPPD
CAS:melanocortin 3 receptor, 189235-81-2; melanocortin 4 receptor, 201099-18-5; neuropeptide Y, 82785-45-3, 83589-17-7; prolactin, 12585-34-1, 50647-00-2, 9002-62-4; Intracellular Signaling Peptides and Proteins; Neuropeptide Y; Neuropeptides; Protein Precursors; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Receptors, Dopamine D2; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; alpha-MSH, 581-05-5; orexin receptors; orexins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01434179_v43_n4_p267_GarciaTornadu

Referencias:

  • Ahima, R.S., Flier, J.S., Leptin (2000) Ann. Rev. Physiol., 62, pp. 413-437
  • Asa, S.L., Kelly, M.A., Grandy, D.K., Low, M.J., Pituitary lactotroph adenomas develop after prolonged lactotroph hyperplasia in dopamine D2 receptor-deficient mice (1999) Endocrinology, 140, pp. 5348-5355
  • Ben-Jonathan, N., Hugo, E.R., Brandebourg, T.D., LaPensee, C.R., Focus on prolactin as a metabolic hormone (2006) Trends Endocrinol. Metab., 17, pp. 110-116
  • Beuckmann, C.T., Yanagisawa, M., Orexins: from neuropeptides to energy homeostasis and sleep/wake regulation (2002) J. Mol. Med., 80, pp. 329-342
  • Bina, K.G., Cincotta, A.H., Dopaminergic agonists normalize elevated hypothalamic neuropeptide Y and corticotropin-releasing hormone, body weight gain, and hyperglycemia in ob/ob mice (2000) Neuroendocrinology, 71, pp. 68-78
  • Bubser, M., Fadel, J.R., Jackson, L.L., Meador-Woodruff, J.H., Jing, D., Deutch, A.Y., Dopaminergic regulation of orexin neurons (2005) Eur. J. Neurosci., 21, pp. 2993-3001
  • Catania, A., Airaghi, L., Colombo, G., Lipton, J.M., Alpha-melanocyte-stimulating hormone in normal human physiology and disease states (2000) Trends Endocrinol. Metab., 11, pp. 304-308
  • Chen, P., Smith, M.S., Regulation of hypothalamic neuropeptide Y messenger ribonucleic acid expression during lactation: role of prolactin (2004) Endocrinology, 145, pp. 823-829
  • Chen, C.L., Dionne, F.T., Roberts, J.L., Regulation of the pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds (1983) Proc. Natl. Acad. Sci. USA, 80, pp. 2211-2215
  • Cheung, C.C., Clifton, D.K., Steiner, R.A., Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus (1997) Endocrinology, 138, pp. 4489-4492
  • Cone, R.D., The central melanocortin system and energy homeostasis (1999) Trends Endocrinol. Metab., 10, pp. 211-216
  • Cone, R.D., Cowley, M.A., Butler, A.A., Fan, W., Marks, D.L., Low, M.J., The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis (2001) Int. J. Obes. Relat. Metab. Disord., 25 (SUPPL. 5), pp. S63-S67
  • Cote, T.E., Felder, R., Kebabian, J.W., Sekura, R.D., Reisine, T., Affolter, H.U., D-2 dopamine receptor-mediated inhibition of pro-opiomelanocortin synthesis in rat intermediate lobe. Abolition by pertussis toxin or activators of adenylate cyclase (1986) J. Biol. Chem., 261, pp. 4555-4561
  • Cowley, M.A., Smart, J.L., Rubinstein, M., Cerdan, M.G., Diano, S., Horvath, T.L., Cone, R.D., Low, M.J., Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus (2001) Nature, 411, pp. 480-484
  • Cristina, C., Diaz-Torga, G., Baldi, A., Gongora, A., Rubinstein, M., Low, M.J., Becu-Villalobos, D., Increased pituitary vascular endothelial growth factor-A in dopaminergic D2 receptor knockout female mice (2005) Endocrinology, 146, pp. 2952-2962
  • Cristina, C., Diaz-Torga, G., Gongora, A., Guida, M.C., Perez-Millan, M.I., Baldi, A., Becu-Villalobos, D., Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice (2007) Am. J. Physiol. Endocrinol. Metab., 293, pp. E1341-E1351
  • da Silva, A.A., Kuo, J.J., Hall, J.E., Role of hypothalamic melanocortin 3/4-receptors in mediating chronic cardiovascular, renal, and metabolic actions of leptin (2004) Hypertension, 43, pp. 1312-1317
  • Dalal, M.A., Schuld, A., Pollmacher, T., Lower CSF orexin A (hypocretin-1) levels in patients with schizophrenia treated with haloperidol compared to unmedicated subjects (2003) Mol. Psychiatry, 8, pp. 836-837
  • de Lecea, L., Kilduff, T.S., Peyron, C., Gao, X., Foye, P.E., Danielson, P.E., Fukuhara, C., Sutcliffe, J.G., The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity (1998) Proc. Natl. Acad. Sci. USA, 95, pp. 322-327
  • Diaz-Torga, G., Feierstein, C., Libertun, C., Gelman, D., Kelly, M.A., Low, M.J., Rubinstein, M., Becu-Villalobos, D., Disruption of the D2 dopamine receptor alters GH and IGF-I secretion and causes dwarfism in male mice (2002) Endocrinology, 143, pp. 1270-1279
  • Elias, C.F., Saper, C.B., Maratos-Flier, E., Tritos, N.A., Lee, C., Kelly, J., Tatro, J.B., Elmquist, J.K., Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area (1998) J. Comp. Neurol., 402, pp. 442-459
  • Fadel, J., Deutch, A.Y., Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area (2002) Neuroscience, 111, pp. 379-387
  • Fan, W., Dinulescu, D.M., Butler, A.A., Zhou, J., Marks, D.L., Cone, R.D., The central melanocortin system can directly regulate serum insulin levels (2000) Endocrinology, 141, pp. 3072-3079
  • Fetissov, S.O., Meguid, M.M., On dopamine, D2 receptor, and Taq1A polymorphism in obesity and anorexia (2009) Nutrition, 25, pp. 132-133
  • Fetissov, S.O., Meguid, M.M., Sato, T., Zhang, L.H., Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake (2002) Am. J. Physiol. Regul. Integr. Comp. Physiol., 283, pp. R905-R910
  • Freemark, M., Fleenor, D., Driscoll, P., Binart, N., Kelly, P.A., Body weight and fat deposition in prolactin receptor-deficient mice (2001) Endocrinology, 142, pp. 532-537
  • Garcia, M.C., Lopez, M., Gualillo, O., Seoane, L.M., Dieguez, C., Senaris, R.M., Hypothalamic levels of NPY, MCH, and prepro-orexin mRNA during pregnancy and lactation in the rat: role of prolactin (2003) FASEB J., 17, pp. 1392-1400
  • Garcia-Tornadu, I., Rubinstein, M., Gaylinn, B.D., Hill, D., Arany, E., Low, M.J., Diaz-Torga, G., Becu-Villalobos, D., GH in the dwarf dopaminergic D2 receptor knockout mouse: somatotrope population, GH release, and responsiveness to GH-releasing factors and somatostatin (2006) J. Endocrinol., 190, pp. 611-619
  • Haynes, W.G., Morgan, D.A., Djalali, A., Sivitz, W.I., Mark, A.L., Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic (1999) Hypertension, 33, pp. 542-547
  • Hillebrand, J.J., de Wied, D., Adan, R.A., Neuropeptides, food intake and body weight regulation: a hypothalamic focus (2002) Peptides, 23, pp. 2283-2306
  • Hurley, D.L., Birch, D.V., Almond, M.C., Estrada, I.J., Phelps, C.J., Reduced hypothalamic neuropeptide Y expression in growth hormone- and prolactin-deficient Ames and Snell dwarf mice (2003) Endocrinology, 144, pp. 4783-4789
  • Kamiji, M.M., Inui, A., Neuropeptide y receptor selective ligands in the treatment of obesity (2007) Endocr. Rev., 28, pp. 664-684
  • Kastin, A.J., Redding, T.W., Hall, R., Besser, G.M., Schally, A.V., Lipid mobilizing hormones of the hypothalamus and pituitary (1975) Pharmacol. Biochem. Behav., 3, pp. 121-126
  • Kelly, M.A., Rubinstein, M., Asa, S.L., Zhang, G., Saez, C., Bunzow, J.R., Allen, R.G., Low, M.J., Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice (1997) Neuron, 19, pp. 103-113
  • Kelly, M.A., Rubinstein, M., Zhang, G., Saez, C., Bunkenburg, B., Zhang, G., Saez, C., Low, M.J., Locomotor activity in D2 dopamine receptor-deficient mice is determined by gene dosage, genetic background, and developmental adaptations (1998) J. Neurosci., 18, pp. 3470-3479
  • Kishi, T., Aschkenasi, C.J., Lee, C.E., Mountjoy, K.G., Saper, C.B., Elmquist, J.K., Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat (2003) J. Comp. Neurol., 457, pp. 213-235
  • Leibowitz, S.F., Brain monoamines and peptides: role in the control of eating behavior (1986) Fed. Proc., 45, pp. 1396-1403
  • Lopez, M., Lage, R., Tung, Y.C., Challis, B.G., Varela, L., Virtue, S., O'Rahilly, S., Coll, A.P., Orexin expression is regulated by alpha-melanocyte-stimulating hormone (2007) J. Neuroendocrinol., 19, pp. 703-707
  • Lubkin, M., Stricker-Krongrad, A., Independent feeding and metabolic actions of orexins in mice (1998) Biochem. Biophys. Res. Commun., 253, pp. 241-245
  • Luukkaa, V., Savontaus, E., Rour, J., Virtanen, K.A., Boss, O., Huhtaniemi, I., Koulu, M., Huupponon, R., Effects of estrous cycle and steroid replacement on the expression of leptin and uncoupling proteins in adipose tissue in the rat (2001) Gynecol. Endocrinol., 15, pp. 103-112
  • Manzanares, J., Toney, T.W., Tian, Y., Eaton, M.J., Moore, K.E., Lookingland, K.J., Sexual differences in the activity of periventricular-hypophysial dopaminergic neurons in rats (1992) Life Sci., 51, pp. 995-1001
  • Monda, M., Viggiano, A.N., Viggiano, A., Viggiano, E., Lanza, A., De, L.V., Hyperthermic reactions induced by orexin A: role of the ventromedial hypothalamus (2005) Eur. J. Neurosci., 22, pp. 1169-1175
  • Naef, L., Woodside, B., Prolactin/leptin interactions in the control of food intake in rats (2007) Endocrinology, 148, pp. 5977-5983
  • Peruzzo, B., Pastor, F.E., Blazquez, J.L., Schobitz, K., Pelaez, B., Amat, P., Rodriguez, E.M., A second look at the barriers of the medial basal hypothalamus (2000) Exp. Brain Res., 132, pp. 10-26
  • Pijl, H., Reduced dopaminergic tone in hypothalamic neural circuits: expression of a "thrifty" genotype underlying the metabolic syndrome? (2003) Eur. J. Pharmacol., 480, pp. 125-131
  • Ramos, E.J., Meguid, M.M., Campos, A.C., Coelho, J.C., Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation (2005) Nutrition, 21, pp. 269-279
  • Sahu, A., Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance (2003) Front. Neuroendocrinol., 24, pp. 225-253
  • Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R.M., Tanaka, H., Williams, S.C., Yanagisawa, M., Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior (1998) Cell, 92, pp. 573-585
  • Samson, W.K., Gosnell, B., Chang, J.K., Resch, Z.T., Murphy, T.C., Cardiovascular regulatory actions of the hypocretins in brain (1999) Brain Res., 831, pp. 248-253
  • Sato, T., Meguid, M.M., Fetissov, S.O., Chen, C., Zhang, L., Hypothalamic dopaminergic receptor expressions in anorexia of tumor-bearing rats (2001) Am. J. Physiol. Regul. Integr. Comp. Physiol., 281, pp. R1907-R1916
  • Sauve, D., Woodside, B., The effect of central administration of prolactin on food intake in virgin female rats is dose-dependent, occurs in the absence of ovarian hormones and the latency to onset varies with feeding-regimen (1996) Brain Res., 729, pp. 75-81
  • Sauve, D., Woodside, B., Neuroanatomical specificity of prolactin-induced hyperphagia in virgin female rats (2000) Brain Res., 868, pp. 306-314
  • Seeley, R.J., Yagaloff, K.A., Fisher, S.L., Burn, P., Thiele, T.E., van Dijk, G., Baskin, D.G., Schwartz, M.W., Melanocortin receptors in leptin effects (1997) Nature, 390, p. 349
  • Silveyra, P., Catalano, P.N., Lux-Lantos, V., Libertun, C., Impact of proestrous milieu on expression of orexin receptors and prepro-orexin in rat hypothalamus and hypophysis: actions of Cetrorelix and Nembutal (2007) Am. J. Physiol. Endocrinol. Metab., 292, pp. E820-E828
  • Taheri, S., Zeitzer, J.M., Mignot, E., The role of hypocretins (orexins) in sleep regulation and narcolepsy (2002) Annu. Rev. Neurosci., 25, pp. 283-313
  • Terry, P., Gilbert, D.B., Cooper, S.J., Dopamine receptor subtype agonists and feeding behavior (1995) Obes. Res., 3 (SUPPL. 4), pp. 515S-523S
  • Trivedi, P., Yu, H., MacNeil, D.J., Van der Ploeg, L.H., Guan, X.M., Distribution of orexin receptor mRNA in the rat brain (1998) FEBS Lett., 438, pp. 71-75

Citas:

---------- APA ----------
García-Tornadú, I., Díaz-Torga, G., Risso, G.S., Silveyra, P., Cataldi, N., Ramirez, M.C., Low, M.J.,..., Becu-Villalobos, D. (2009) . Hypothalamic orexin, OX1, αMSH, NPY and MCRs expression in dopaminergic D2R knockout mice. Neuropeptides, 43(4), 267-274.
http://dx.doi.org/10.1016/j.npep.2009.06.002
---------- CHICAGO ----------
García-Tornadú, I., Díaz-Torga, G., Risso, G.S., Silveyra, P., Cataldi, N., Ramirez, M.C., et al. "Hypothalamic orexin, OX1, αMSH, NPY and MCRs expression in dopaminergic D2R knockout mice" . Neuropeptides 43, no. 4 (2009) : 267-274.
http://dx.doi.org/10.1016/j.npep.2009.06.002
---------- MLA ----------
García-Tornadú, I., Díaz-Torga, G., Risso, G.S., Silveyra, P., Cataldi, N., Ramirez, M.C., et al. "Hypothalamic orexin, OX1, αMSH, NPY and MCRs expression in dopaminergic D2R knockout mice" . Neuropeptides, vol. 43, no. 4, 2009, pp. 267-274.
http://dx.doi.org/10.1016/j.npep.2009.06.002
---------- VANCOUVER ----------
García-Tornadú, I., Díaz-Torga, G., Risso, G.S., Silveyra, P., Cataldi, N., Ramirez, M.C., et al. Hypothalamic orexin, OX1, αMSH, NPY and MCRs expression in dopaminergic D2R knockout mice. Neuropeptides. 2009;43(4):267-274.
http://dx.doi.org/10.1016/j.npep.2009.06.002