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dc.contributor.author
Pérez Millán, María Inés
dc.contributor.author
Luque, Guillermina Maria
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Ramirez, Maria Cecilia
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Noain, Daniela Maria Clara
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Ornstein, Ana Maria
dc.contributor.author
Rubinstein, Marcelo
dc.contributor.author
Becu, Damasia
dc.date.available
2017-08-24T20:35:41Z
dc.date.issued
2014-03-01
dc.identifier.citation
Pérez Millán, María Inés; Luque, Guillermina Maria; Ramirez, Maria Cecilia; Noain, Daniela Maria Clara; Ornstein, Ana Maria; et al.; Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice; Endocrine Society; Endocrinology; 155; 3; 1-3-2014; 829-839
dc.identifier.issn
0013-7227
dc.identifier.uri
http://hdl.handle.net/11336/22978
dc.description.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 evidenced increased food intake by three months of age and, from five months onwards their body weights were heavier. A marked increment in fat depots, adipocyte size, serum triglyceride and non-esterified fatty acid levels, and a decrease in lipolytic enzymes in adipose tissue were evidenced. 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 mouse). 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 patho-physiological mechanisms otherwise masked in null allele mutants or in animals treated with pervasive pharmacological agents.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Endocrine Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Lacdrd2ko
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Lactotrope
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Food Intake
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Hyperprolactinemia
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Glucose Intolerance
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Bioquímica y Biología Molecular
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-08-08T14:28:56Z
dc.identifier.eissn
1945-7170
dc.journal.volume
155
dc.journal.number
3
dc.journal.pagination
829-839
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Los Angeles
dc.description.fil
Fil: Pérez Millán, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Luque, Guillermina Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Ramirez, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
dc.description.fil
Fil: Ornstein, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina
dc.description.fil
Fil: Becu, Damasia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.journal.title
Endocrinology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2013-1707
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1210/en.2013-1707
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/pmid/24424036
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