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

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    337 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

    ASJC Scopus subject areas

    • Neuroscience(all)

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