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Abstract:

Prolactin, a pleiotropic hormone secreted by lactotropes, has reproductive and metabolic functions. Chronically elevated prolactin levels increase food intake, but in some hyperprolactinemic states such as in the global dopamine D2 receptor (D2R) knockout mouse, food intake is not increased. Here, we conduct a cell-specific genetic dissection study using conditional mutant mice that selectively lack D2Rs from pituitary lactotropes (lacDrd2KO) to evaluate the role of elevated prolactin levels without any confounding effect of central D2Rs on motor and reward mechanisms related to food intake. LacDrd2KO female mice exhibited chronic hyperprolactinemia, pituitary hyperplasia, and a preserved GH axis. In addition, lacDrd2KO female but not male mice showed increased food intake by 3 months of age, and from 5 months onward their body weights were heavier. Marked increments in fat depots, adipocyte size, serum triglycerides, and nonesterified fatty acid levels and a decrease in lipolytic enzymes in adipose tissue were seen. Furthermore, lacDrd2KO female mice had glucose intolerance but a preserved response to insulin. In the hypothalamus, Npy mRNA expression was increased, and Pomc and Ppo mRNA levels were unaltered (in contrast to results in global D2R knockout mice). Thus, the orexigenic effect of prolactin and its action on hypothalamic Npy expression were fully evidenced, leading to increased food intake and adiposity. Our results highlight the metabolic role of prolactin and illustrate the value of studying cell-specific mutant mice to disentangle the pathophysiological mechanisms otherwise masked in null allele mutants or in animals treated with pervasive pharmacological agents. Copyright © 2014 by the Endocrine Society.

Registro:

Documento: Artículo
Título:Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
Autor:Millan, M.I.P.; Luque, G.M.; Ramirez, M.C.; Noain, D.; Ornstein, A.M.; Rubinstein, M.; Becu-Villalobos, D.
Filiación:Laboratory of Pituitary Regulation, Institute of Biology and Experimental Medicine, Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Buenos Aires 1428, Argentina
Instituto de Investigaciones en Ingeniería Genética Y Biología Molecular, CONICET, Buenos Aires, Argentina
Departamento de Fisiología, Y Biología Molecular Y Celular, Facultad de Ciencias Exactas Y Naturales, University of Buenos Aires, Buenos Aires 1428, Argentina
Palabras clave:dopamine 2 receptor; fatty acid; insulin; prolactin; adipocyte; adipose tissue; animal experiment; animal model; article; body weight; cell disruption; controlled study; fatty acid blood level; female; food intake; gene disruption; gene expression; glucose intolerance; hyperplasia; hyperprolactinemia; hypothalamus; lipid storage; male; mouse; nonhuman; null allele; obesity; pathophysiology; priority journal; prolactin blood level; prolactin secreting cell; triacylglycerol blood level; weight gain; Adipose Tissue; Adiposity; Animals; Body Weight; Eating; Estrous Cycle; Female; Genotype; Glucose Intolerance; Glucose Tolerance Test; Insulin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pituitary Gland; Prolactin; Receptors, Dopamine D2
Año:2014
Volumen:155
Número:3
Página de inicio:829
Página de fin:839
DOI: http://dx.doi.org/10.1210/en.2013-1707
Título revista:Endocrinology
Título revista abreviado:Endocrinology
ISSN:00137227
CODEN:ENDOA
CAS:insulin, 9004-10-8; prolactin, 12585-34-1, 50647-00-2, 9002-62-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v155_n3_p829_Millan

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Citas:

---------- APA ----------
Millan, M.I.P., Luque, G.M., Ramirez, M.C., Noain, D., Ornstein, A.M., Rubinstein, M. & Becu-Villalobos, D. (2014) . Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice. Endocrinology, 155(3), 829-839.
http://dx.doi.org/10.1210/en.2013-1707
---------- CHICAGO ----------
Millan, M.I.P., Luque, G.M., Ramirez, M.C., Noain, D., Ornstein, A.M., Rubinstein, M., et al. "Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice" . Endocrinology 155, no. 3 (2014) : 829-839.
http://dx.doi.org/10.1210/en.2013-1707
---------- MLA ----------
Millan, M.I.P., Luque, G.M., Ramirez, M.C., Noain, D., Ornstein, A.M., Rubinstein, M., et al. "Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice" . Endocrinology, vol. 155, no. 3, 2014, pp. 829-839.
http://dx.doi.org/10.1210/en.2013-1707
---------- VANCOUVER ----------
Millan, M.I.P., Luque, G.M., Ramirez, M.C., Noain, D., Ornstein, A.M., Rubinstein, M., et al. Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice. Endocrinology. 2014;155(3):829-839.
http://dx.doi.org/10.1210/en.2013-1707