New Insights into the Endocrine and Metabolic Roles of Dopamine D2 Receptors Gained from the Drd2 –/– Mouse

ISABEL GARCIA-TORNADÚ MARIA INES PEREZ-MILLAN VICTORIA RECOUVREUX MARIA CECILIA RAMIREZ GUILLERMINA LUQUE GABRIELA SOFIA RISSO ANA MARIA ORNSTEIN CAROLINA CRISTINA GRACIELA DIAZ-TORGA DAMASIA BECU-VILLALOBOS

NEUROENDOCRINOLOGY

KARGER

Año: 2010 vol. 92 p. 207 - 214

0028-3835

Dopamine D2 receptor (D2R) participation in prolactin regulationis well documented, but the role of D2Rs in the controlof other hormones involved in growth, food intake and glucosemetabolism has not been extensively studied. Thestudy of D2R knockout mice ( Drd2 –/– ) puts forward new insightsinto the role of the D2R in growth hormone (GH)-releasinghormone-GH regulation, peptides involved in foodintake, glucose homeostasis, as well as in prolactinoma development.The expected phenotype of chronic hyperprolactinemiaand prolactinoma development was found in theDrd2– /– mouse, and this model constitutes a valuable tool inthe study of dopamine-resistant prolactinomas. Unexpectedly,these mice were growth retarded, and the importanceof functional hypothalamic D2Rs in the neonatal period wasrevealed. In the Drd2 –/– mouse there was a failure of highneonatal GH levels and therefore the expansion of pituitarysomatotropes was permanently altered. These mice also hadincreased food intake, and a sexually dimorphic participationof the D2R in food intake regulation is suggested. Theeffect described is probably secondary to D2R regulation ofprolactin secretion. Furthermore, the negative modulationof D2Rs on -melanocyte-stimulating hormone release andpositive action on the hypothalamic expression of orexinsreveals the complex D2R regulation of food intake. Finally,pancreatic D2Rs inhibit glucose-stimulated insulin release.Lack of dopaminergic inhibition throughout developmentin the Drd2 –/– mouse may exert a gradual deteriorating effecton insulin homeostasis, so that eventually glucose intolerancedevelops. These results highlight the complex endocrineactions of the D2Rs at different levels, hypothalamus,pituitary or pancreas, which function to improve fitness, reproductivesuccess and survival.Copyright © 2010 S. Karger AG, Basel