Pituitary adenomas are caused by dysregulation of cell proliferation and are classified according to the hormones they produce. Expression, activation and function of the Notch system in normal and pituitary tumors require deeper studies. Therefore, we aimed at profiling the Notch receptor expression pattern in different pituitary tumor models.Comparing prolactinoma xenograft model and two rat prolactinoma cell lines (GH3 and MMQ) with normal rat gland, Notch-2 showed the highest expression among the four receptors. Interestingly, normal pituitary showed higher levels of all Notch receptors compared to tumor cells. In accordance, we determined a downregulation of Notch-1 and Notch-3 protein levels by immunohistochemistry in the rat prolactinomas generated invivo by chronic estrogen treatment compared to normal pituitary. Notch1 reduction was confirmed by Western Blot. Notch1-4 mRNA levels were analyzed by RT-qPCR in the mouse corticotroph tumor cell line AtT20 and in adult mouse normal pituitary. Notch-4 showed lower levels than the other three receptors in both cases. Interestingly, lower levels of Notch-3 and Notch-4 but no differences in Notch-1 or Notch-2 were determined in AtT20cells compared to the normal gland. Western Blot experiments also showed this pattern. When studying human pituitary adenomas, Notch mRNA levels showed variable patterns among the different adenoma types. There was a trend of higher Notch-3 protein level in ACTH-secreting adenomas relative to other adenoma types. Notch-3 was detected in normal pituitary as well. Jagged-1 and Hes-1 were also detected in adenoma samples.