ANTIPROLIFERATIVE ROLE OF DOPAMINE - LOSS OF D-2 RECEPTORS CAUSES HORMONAL DYSFUNCTION AND PITUITARY HYPERPLASIA

The function of dopamine (DA) in the nervous system is paralleled by i ts neuroendocrine control of pituitary gland functions. Here, we docum ent the neuroendocrine function of dopamine by studying the pituitary gland of mice lacking DA D-2 receptors (D2R). These mice present a str iking, progressive increase in lactotroph number, which ultimately lea ds to tumors in aged animals. Females develop tumors much earlier than males. An estrogen-mediated lactotroph proliferation cannot account f or this sexual dimorphism, since D2R-null females are hypoestrogenic a nd, thus, have estrogen levels similar to males. In contrast, prolacti n levels are six times higher in females than in males. We show that a ctive prolactin receptors are present in the pituitary and their expre ssion increases in concomitance with tumor expansion. These results po int to prolactin as an autocrine proliferative factor in the pituitary gland. Additionally, they demonstrate an antiproliferative function f or DA regulated through D-2 receptor activation.