title: Central dopamine D2 receptors regulate growth-hormone-dependent body growth and pheromone signaling to conspecific males.
abstract: Competition between adult males for limited resources such as food and receptive females is shaped by the male pattern of pituitary growth hormone (GH) secretion that determines body size and the production of urinary pheromones involved in male-to-male aggression. In the brain, dopamine (DA) provides incentive salience to stimuli that predict the availability of food and sexual partners. Although the importance of the GH axis and central DA neurotransmission in social dominance and fitness is clearly appreciated, the two systems have always been studied unconnectedly. Here we conducted a cell-specific genetic dissection study in conditional mutant mice that selectively lack DA D2 receptors (D2R) from pituitary lactotropes (lacDrd2KO) or neurons (neuroDrd2KO). Whereas lacDrd2KO mice developed a normal GH axis, neuroDrd2KO mice displayed fewer somatotropes; reduced hypothalamic Ghrh expression, pituitary GH content, and serum IGF-I levels; and exhibited reduced body size and weight. As a consequence of a GH axis deficit, neuroDrd2KO adult males excreted low levels of major urinary proteins and their urine failed to promote aggression and territorial behavior in control male challengers, in contrast to the urine taken from control adult males. These findings reveal that central D2Rs mediate a neuroendocrine-exocrine cascade that controls the maturation of the GH axis and downstream signals that are critical for fitness, social dominance, and competition between adult males.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, C1428ADN Buenos Aires, Argentina.
authors.forename: Daniela
authors.initials: D
authors.lastname: Noaín
authors.forename: M Inés
authors.initials: MI
authors.lastname: Pérez-Millán
authors.forename: Estefanía P
authors.initials: EP
authors.lastname: Bello
authors.forename: Guillermina M
authors.initials: GM
authors.lastname: Luque
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Casas Cordero
authors.forename: Diego M
authors.initials: DM
authors.lastname: Gelman
authors.forename: Marcela
authors.initials: M
authors.lastname: Peper
authors.forename: Isabel García
authors.initials: IG
authors.lastname: Tornadu
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
authors.forename: Damasia
authors.initials: D
authors.lastname: Becú-Villalobos
authors.forename: Marcelo
authors.initials: M
authors.lastname: Rubinstein
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics; D049628:Body Size / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D016022:Case-Control Studies; D002389:Catatonia / Q000139:chemically induced / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010675:Pheromones / Q000652:urine; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D011863:Radioimmunoassay; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012930:Social Dominance; D013731:Territoriality; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D001549:Benzamides; D018492:Dopamine Antagonists; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D020319:Oligodeoxyribonucleotides, Antisense; D010675:Pheromones; D011506:Proteins; D017448:Receptors, Dopamine D2; C035737:major urinary proteins; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone; D006220:Haloperidol; C030265:nemonapride
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