Context: Mimecan, a secretory protein, belongs to a family of small leucine-rich proteoglycans (SLRPs). The physiological functions of mimecan have not been fully understood. Objective: We hypothesize that the mimecan gene expressed in the human pituitary and regulated by pituitary transcription factor-1 (Pit-1) might act as a marker for diagnosing pituitary tumors. Design: The clinical aspect of our work was a cross-sectional study. Setting and Patients: In total, 20 pituitary tumor samples were collected from January 1, 2002, to December 30, 2002, in Ruijin Hospital, Shanghai, China. Intervention: The number of pituitary tumors was limited. Collection of more pituitary tumor samples for additional observation will be necessary. Main Outcome Measures: The main outcomes were measured by Northern blot, in situ hybridization, immunohistochemical analysis, and so on. Results: The mimecan gene was expressed at a moderate level in the mouse pituitary gland by Northern blot analysis. Expression of mimecan mRNA and protein is also observed in the human anterior pituitary gland. Luciferase reporter analysis and electrophoretic mobility shift assays show that Pit-1 activates the human mimecan promoter through Pit-1 response element sites. In addition, our data also show that almost all the ACTH- or GH-positive pituitary tumors likely express mimecan protein, and only a portion of prolactin-, TSH-, FSH-, and LH-positive pituitary tumors express mimecan protein. Conclusions: This work provides insight into the regulating mechanism of mimecan in pituitary and suggests that mimecan may be an unidentified pituitary secretory protein, and certain pituitary cells secreting ACTH or GH also secrete mimecan. (J Clin Endocrinol Metab 90: 6657-6664, 2005)