Dopamine regulates the synthesis and secretion of prolactin and α-MSH/β-endorphin in lactotrophs and melanotrophs, respectively. While a predominant dopamine receptor, D2R, is known to be expressed in both the anterior and intermediate lobes of the pituitary gland, no previous immunohistochemical studies have shown the existence of D2R in the plasma membrane of pituitary endocrine cells. The present study clearly demonstrated a selective localization of the D2R immunoreactivity in primary cilia of lactotrophs and melanotrophs in the mouse adenohypophysis. Another immunoreactivity of D2R was found along the plasma membrane of melanotrophs. The intensity of immunoreactivity for D2R in the primary cilia of lactrotrophs changed during the estrous cycle and with genital conditions in contrast to a consistent immunolabeling in the melanotrophs. Since there is accumulating evidence that the primary cilium functions as a sensory device at a cellular level, the D2R-expressing primary cilia in the pituitary gland may be involved in the sensation of dopamine and dopaminergic compounds-though their involvement differs between the anterior and intermediate lobes.Dopamine is well established as a primary inhibitor of both prolactin secretion (6) and the proliferation of lactotrophs (1, 13). Dopamine is released at the median eminence and conveyed by the hypothalamic portal system to regulate the activities of pituitary lactotrophs mainly via the type 2 dopamine receptor (D2R). Accordingly, D2R knockout mice display a phenotype characterized by chronic hyper-prolactinemia and the hyperplasia of lactotrophs (16,25). Although dopamine must exert its actions by binding to specific membrane receptors on pituitary endocrine cells, previous immunohistochemical studies of normal and tumoral lactotrophs have detected D2R immunoreactivities in the cytoplasm but not in the plasma membrane (18,41,48). This is an inconsistent finding concerning the subcellular localization of D2R-though we sometimes experience such a discrepancy with the immunostaining of membrane-bound receptors. The pituitary intermediate lobe is also under the control of dopamine (10)(11)(12)17) and expresses D2R at a high density, unlike the anterior lobe (3). In situ hybridization analyses for D2R mRNA and radioligand binding assays in rats have demonstrated a condensed expression of D2R or dopamine binding sites in the intermediate lobe (28,32,35). The intermediate lobe morphologically differs from the anterior lobe by having rich innervation and poor vascularization (4, 26, 27) and being composed of essentially one type of endocrine cell, melanotrophs. The melanotrophs receive dopamine input from tuberohypophyseal neurons that actually terminate within the intermediate lobe (4). Dopamine has been experimentally shown to decrease the capacity of the intermediate lobe to synthesize pro-opiomelanocortin