Background: It has been suggested that the dopaminergic system is involved in the inhibitory control of secretion of pituitary hormones and in the regulation of motor function in the striatum. To elucidate the specific role of the dopamine D2 receptor (D2R) in the pituitary and brain, we generated D2R deficient (D2R mutant) mice using the gene targeting method.
Results: Electrophysiological studies as well as ligand binding assays show no functional D2R in mutant mice. The D2R mutant mice display a hypoactivity and a slow, creeping movement. The expression of enkephalin mRNA in the striatum is increased in the mutant mice, but not that of dynorphin and substance P. D2R mutant mice have significantly darker coat colour than their wild-type littermates and show an elevation of plasma alpha-melanocyte stimulating hormone (alpha-MSH) levels. We found corresponding hyperplastic changes of intermediate lobe of the pituitary and the increased expression of pro opiomelanocortin (POMC) in the pituitary in D2R mutant mice.
Conclusions: D2R plays a critical role in the inhibitory regulation of endocrine cell proliferation and the transcription of POMC mRNA, and consequently in the regulation of alpha-MSH in plasma. D2R might be involved in the regulation of enkephalin expression in the striatum, and hence might affect the movement and the behaviour.