title: Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice.
abstract: Dopamine secreted from hypophysial hypothalamic neurons is a principal inhibitory regulator of pituitary hormone secretion. Mice with a disrupted D2 dopamine receptor gene had chronic hyperprolactinemia and developed anterior lobe lactotroph hyperplasia without evidence of adenomatous transformation. Unexpectedly, the mutant mice had no hyperplasia of the intermediate lobe melanotrophs. Aged female D2 receptor -/- mice developed uterine adenomyosis in response to prolonged prolactin exposure. These data reveal a critical role of hypothalamic dopamine in controlling pituitary growth and support a multistep mechanism for the induction and perpetuation of lactotroph hyperplasia, involving the lack of dopamine signaling, a low androgen/estrogen ratio, and a final autocrine or paracrine "feed-forward" stimulation of mitogenesis, probably by prolactin itself.
authors.affiliation: Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Kelly
authors.forename: M
authors.initials: M
authors.lastname: Rubinstein
authors.forename: S L
authors.initials: SL
authors.lastname: Asa
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Saez
authors.forename: J R
authors.initials: JR
authors.lastname: Bunzow
authors.forename: R G
authors.initials: RG
authors.lastname: Allen
authors.forename: R
authors.initials: R
authors.lastname: Hnasko
authors.forename: N
authors.initials: N
authors.lastname: Ben-Jonathan
authors.forename: D K
authors.initials: DK
authors.lastname: Grandy
authors.forename: M J
authors.initials: MJ
authors.lastname: Low
mesh_terms: D000818:Animals; D005260:Female; D006965:Hyperplasia / Q000378:metabolism*; D006966:Hyperprolactinemia / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010902:Pituitary Gland / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012737:Sex Factors
chemical_list: D017448:Receptors, Dopamine D2; D011388:Prolactin