Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice

Michele A. Kelly, Marcelo Rubinstein, Sylvia L. Asa, Ge Zhang, Carmen Saez, James R. Bunzow, Richard G. Allen, Robert Hnasko, Nira Ben-Jonathan, David K. Grandy, Malcolm J. Low

Research output: Contribution to journalArticlepeer-review

346 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)103-113
Number of pages11
JournalNeuron
Volume19
Issue number1
DOIs
StatePublished - Jul 1997
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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