PITUITARY LACTOTROPH HYPERPLASIA AND CHRONIC HYPERPROLACTINEMIA IN DOPAMINE D2 RECEPTOR-DEFICIENT MICE

Dopamine secreted from hypophysial hypothalamic neurons is a principal inhibitory regulator of pituitary hormone secretion. Mice with a disr upted D2 dopamine receptor gene had chronic hyperprolactinemia and dev eloped anterior robe lactotroph hyperplasia without evidence of adenom atous transformation. Unexpectedly, the mutant mice had no hyperplasia of the intermediate robe melanotrophs. Aged female D2 receptor -/- mi ce developed uterine adenomyosis in response to prolonged prolactin ex posure. 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 l ack of dopamine signaling, a low androgen/estrogen ratio, and a final autocrine or paracrine ''feed-forward'' stimulation of mitogenesis, pr obably by prolactin itself.