New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse
Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of other hormones involved in growth, food intake and glucose metabolism has not been extensively studied. The study of D2R knockout mice (Drd2-/-) puts forward new insights into...
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todo:paper_00283835_v92_n4_p207_GarciaTornadu2023-10-03T14:38:59Z New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse Garcia-Tornadú, I. Perez-Millan, M.I. Recouvreux, V. Ramirez, M.C. Luque, G. Risso, G.S. Ornstein, A.M. Cristina, C. Diaz-Torga, G. Becu-Villalobos, D. Dopamine receptor Food intake Glucose metabolism Growth hormone Growth hormone-releasing hormone Insulin Pancreas Prolactin Transgenic mice dopamine 2 receptor adenohypophysis endocrine function food intake glucose homeostasis glucose intolerance glucose metabolism hyperprolactinemia insulin release metabolic regulation newborn period nonhuman priority journal prolactin release prolactinoma review Animals Eating Endocrine System Growth Hormone Growth Hormone-Releasing Hormone Metabolism Mice Mice, Knockout Prolactin Receptors, Dopamine D2 Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of other hormones involved in growth, food intake and glucose metabolism has not been extensively studied. The study of D2R knockout mice (Drd2-/-) puts forward new insights into the role of the D2R in growth hormone (GH)-releasing hormone-GH regulation, peptides involved in food intake, glucose homeostasis, as well as in prolactinoma development. The expected phenotype of chronic hyperprolactinemia and prolactinoma development was found in the Drd2-/- mouse, and this model constitutes a valuable tool in the study of dopamine-resistant prolactinomas. Unexpectedly, these mice were growth retarded, and the importance of functional hypothalamic D2Rs in the neonatal period was revealed. In the Drd2-/- mouse there was a failure of high neonatal GH levels and therefore the expansion of pituitary somatotropes was permanently altered. These mice also had increased food intake, and a sexually dimorphic participation of the D2R in food intake regulation is suggested. The effect described is probably secondary to D2R regulation of prolactin secretion. Furthermore, the negative modulation of D2Rs on α-melanocyte-stimulating hormone release and positive action on the hypothalamic expression of orexins reveals the complex D2R regulation of food intake. Finally, pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development in the Drd2-/- mouse may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. These results highlight the complex endocrine actions of the D2Rs at different levels, hypothalamus, pituitary or pancreas, which function to improve fitness, reproductive success and survival. Copyright © 2010 S. Karger AG, Basel. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00283835_v92_n4_p207_GarciaTornadu |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Dopamine receptor Food intake Glucose metabolism Growth hormone Growth hormone-releasing hormone Insulin Pancreas Prolactin Transgenic mice dopamine 2 receptor adenohypophysis endocrine function food intake glucose homeostasis glucose intolerance glucose metabolism hyperprolactinemia insulin release metabolic regulation newborn period nonhuman priority journal prolactin release prolactinoma review Animals Eating Endocrine System Growth Hormone Growth Hormone-Releasing Hormone Metabolism Mice Mice, Knockout Prolactin Receptors, Dopamine D2 |
| spellingShingle |
Dopamine receptor Food intake Glucose metabolism Growth hormone Growth hormone-releasing hormone Insulin Pancreas Prolactin Transgenic mice dopamine 2 receptor adenohypophysis endocrine function food intake glucose homeostasis glucose intolerance glucose metabolism hyperprolactinemia insulin release metabolic regulation newborn period nonhuman priority journal prolactin release prolactinoma review Animals Eating Endocrine System Growth Hormone Growth Hormone-Releasing Hormone Metabolism Mice Mice, Knockout Prolactin Receptors, Dopamine D2 Garcia-Tornadú, I. Perez-Millan, M.I. Recouvreux, V. Ramirez, M.C. Luque, G. Risso, G.S. Ornstein, A.M. Cristina, C. Diaz-Torga, G. Becu-Villalobos, D. New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse |
| topic_facet |
Dopamine receptor Food intake Glucose metabolism Growth hormone Growth hormone-releasing hormone Insulin Pancreas Prolactin Transgenic mice dopamine 2 receptor adenohypophysis endocrine function food intake glucose homeostasis glucose intolerance glucose metabolism hyperprolactinemia insulin release metabolic regulation newborn period nonhuman priority journal prolactin release prolactinoma review Animals Eating Endocrine System Growth Hormone Growth Hormone-Releasing Hormone Metabolism Mice Mice, Knockout Prolactin Receptors, Dopamine D2 |
| description |
Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of other hormones involved in growth, food intake and glucose metabolism has not been extensively studied. The study of D2R knockout mice (Drd2-/-) puts forward new insights into the role of the D2R in growth hormone (GH)-releasing hormone-GH regulation, peptides involved in food intake, glucose homeostasis, as well as in prolactinoma development. The expected phenotype of chronic hyperprolactinemia and prolactinoma development was found in the Drd2-/- mouse, and this model constitutes a valuable tool in the study of dopamine-resistant prolactinomas. Unexpectedly, these mice were growth retarded, and the importance of functional hypothalamic D2Rs in the neonatal period was revealed. In the Drd2-/- mouse there was a failure of high neonatal GH levels and therefore the expansion of pituitary somatotropes was permanently altered. These mice also had increased food intake, and a sexually dimorphic participation of the D2R in food intake regulation is suggested. The effect described is probably secondary to D2R regulation of prolactin secretion. Furthermore, the negative modulation of D2Rs on α-melanocyte-stimulating hormone release and positive action on the hypothalamic expression of orexins reveals the complex D2R regulation of food intake. Finally, pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development in the Drd2-/- mouse may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. These results highlight the complex endocrine actions of the D2Rs at different levels, hypothalamus, pituitary or pancreas, which function to improve fitness, reproductive success and survival. Copyright © 2010 S. Karger AG, Basel. |
| format |
JOUR |
| author |
Garcia-Tornadú, I. Perez-Millan, M.I. Recouvreux, V. Ramirez, M.C. Luque, G. Risso, G.S. Ornstein, A.M. Cristina, C. Diaz-Torga, G. Becu-Villalobos, D. |
| author_facet |
Garcia-Tornadú, I. Perez-Millan, M.I. Recouvreux, V. Ramirez, M.C. Luque, G. Risso, G.S. Ornstein, A.M. Cristina, C. Diaz-Torga, G. Becu-Villalobos, D. |
| author_sort |
Garcia-Tornadú, I. |
| title |
New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse |
| title_short |
New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse |
| title_full |
New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse |
| title_fullStr |
New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse |
| title_full_unstemmed |
New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2-/- mouse |
| title_sort |
new insights into the endocrine and metabolic roles of dopamine d2 receptors gained from the drd2-/- mouse |
| url |
http://hdl.handle.net/20.500.12110/paper_00283835_v92_n4_p207_GarciaTornadu |
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