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

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, w...

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Autores principales:	Millan, M.I.P., Luque, G.M., Ramirez, M.C., Noain, D., Ornstein, A.M., Rubinstein, M., Becu-Villalobos, D.
Formato:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00137227_v155_n3_p829_Millan
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00137227_v155_n3_p829_Millan2023-10-03T14:11:24Z Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice Millan, M.I.P. Luque, G.M. Ramirez, M.C. Noain, D. Ornstein, A.M. Rubinstein, M. Becu-Villalobos, D. 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 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. Fil:Noain, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00137227_v155_n3_p829_Millan
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Millan, M.I.P. Luque, G.M. Ramirez, M.C. Noain, D. Ornstein, A.M. Rubinstein, M. Becu-Villalobos, D. Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
topic_facet	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
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 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.
format	JOUR
author	Millan, M.I.P. Luque, G.M. Ramirez, M.C. Noain, D. Ornstein, A.M. Rubinstein, M. Becu-Villalobos, D.
author_facet	Millan, M.I.P. Luque, G.M. Ramirez, M.C. Noain, D. Ornstein, A.M. Rubinstein, M. Becu-Villalobos, D.
author_sort	Millan, M.I.P.
title	Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
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
url	http://hdl.handle.net/20.500.12110/paper_00137227_v155_n3_p829_Millan
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Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice

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