Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice

Autores
Pérez Millán, María Inés; Luque, Guillermina Maria; Ramirez, Maria Cecilia; Noain, Daniela Maria Clara; Ornstein, Ana Maria; Rubinstein, Marcelo; Becu, Damasia
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
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
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
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
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
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
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
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
Materia
Lacdrd2ko
Lactotrope
Food Intake
Hyperprolactinemia
Glucose Intolerance
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/22978
Acceder
id CONICETDig_f55bbf2c622fa3e209794f641087c1f7
oai_identifier_str oai:ri.conicet.gov.ar:11336/22978
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female micePérez Millán, María InésLuque, Guillermina MariaRamirez, Maria CeciliaNoain, Daniela Maria ClaraOrnstein, Ana MariaRubinstein, MarceloBecu, DamasiaLacdrd2koLactotropeFood IntakeHyperprolactinemiaGlucose Intolerancehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Prolactin, 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.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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaFil: 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; ArgentinaEndocrine Society2014-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/22978Pérez 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; 829-8390013-72271945-7170CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2013-1707info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2013-1707info:eu-repo/semantics/altIdentifier/pmid/24424036info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:19:54Zoai:ri.conicet.gov.ar:11336/22978instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:19:54.467CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
title Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
spellingShingle Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
Pérez Millán, María Inés
Lacdrd2ko
Lactotrope
Food Intake
Hyperprolactinemia
Glucose Intolerance
title_short Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
title_full Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
title_fullStr Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
title_full_unstemmed Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
title_sort Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
dc.creator.none.fl_str_mv Pérez Millán, María Inés
Luque, Guillermina Maria
Ramirez, Maria Cecilia
Noain, Daniela Maria Clara
Ornstein, Ana Maria
Rubinstein, Marcelo
Becu, Damasia
author Pérez Millán, María Inés
author_facet Pérez Millán, María Inés
Luque, Guillermina Maria
Ramirez, Maria Cecilia
Noain, Daniela Maria Clara
Ornstein, Ana Maria
Rubinstein, Marcelo
Becu, Damasia
author_role author
author2 Luque, Guillermina Maria
Ramirez, Maria Cecilia
Noain, Daniela Maria Clara
Ornstein, Ana Maria
Rubinstein, Marcelo
Becu, Damasia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Lacdrd2ko
Lactotrope
Food Intake
Hyperprolactinemia
Glucose Intolerance
topic Lacdrd2ko
Lactotrope
Food Intake
Hyperprolactinemia
Glucose Intolerance
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
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
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
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
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
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
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
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
description 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.
publishDate 2014
dc.date.none.fl_str_mv 2014-03-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/22978
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
0013-7227
1945-7170
CONICET Digital
CONICET
url http://hdl.handle.net/11336/22978
identifier_str_mv 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
0013-7227
1945-7170
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2013-1707
info:eu-repo/semantics/altIdentifier/doi/10.1210/en.2013-1707
info:eu-repo/semantics/altIdentifier/pmid/24424036
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Endocrine Society
publisher.none.fl_str_mv Endocrine Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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