Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter.
Deletion of the dopamine transporter (DAT) results in increased dopaminergic tone, anterior pituitary hypoplasia, dwarfism, and an inability to lactate. DAT elimination alters the spatial distribution and dramatically reduces the numbers of lactotrophs and somatotrophs in the pituitary. Despite having normal circulating levels of growth hormone and prolactin in blood, hypoplastic glands from DAT-/- mice fail to respond to secretagog stimulation. The effects of DAT deletion on pituitary function result from elevated DA levels that down-regulate the lactotroph D2 DA receptors and depress hypothalamic growth hormone-releasing hormone content. These results reveal an unexpected and important role or DA in the control of developmental events in the pituitary gland and assign a critical role for hypothalamic DA reuptake in regulating these events.
Bossé
R
R
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Fumagalli
F
F
Jaber
M
M
Giros
B
B
Gainetdinov
R R
RR
Wetsel
W C
WC
Missale
C
C
Caron
M G
MG
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D004392:Dwarfism / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins; D010900:Pituitary Diseases / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493215:Slc6a3 protein, mouse; D004298:Dopamine