Genetic disruption of dopamine production results in pituitary adenomas and severe prolactinemia.
BACKGROUND
Dopamine release from tuberoinfundibular dopamine neurons into the median eminence activates dopamine-D2 receptors in the pituitary gland where it inhibits lactotroph function.


METHODS
We have previously described genetic dopamine-deficient mouse models which lack the ability to synthesize dopamine. Because these animals require daily treatment with 3,4-L-dihydroxyphenylalanine (L-dopa) to survive, it has not been possible to examine the consequences of chronic loss of dopamine on pituitary physiology. We use viral-mediated gene transfer to selectively restore dopamine to the dorsal striatum of dopamine-deficient mice which allows the mice to survive without L-dopa.


RESULTS
We find that mice chronically lacking tuberoinfundibular dopamine secrete large amounts of prolactin due to the development of severely enlarged pituitaries composed principally of hyperplastic hypertrophic lactotrophs and multifocal prolactinomas. In addition, these mice have elevated serum growth hormone levels and aged males develop hypertrophy of the seminal vesicles.


CONCLUSIONS
Our observations are consistent with the hypothesis that hypothalamic dopamine is a critical inhibitor of lactotroph proliferation and suggest additional roles for dopamine in the regulation of pituitary function.
Hnasko
Thomas S
TS
Graduate Program in Neurobiology and Behavior, Children's Hospital and Regional Medical Center, University of Washington, Seattle, WA 98195, USA.
Hnasko
Robert M
RM
Sotak
Bethany N
BN
Kapur
Raj P
RP
Palmiter
Richard D
RD
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism; D011388:Prolactin / Q000097:blood* / Q000378:metabolism
D011388:Prolactin; D004298:Dopamine