The role of Notch and Hedgehog signaling pathways in pituitary development and pathogenesis of pituitary adenomas.

Pituitary adenomas are usually benign tumors that cause symptoms by compression of surrounding structures or impaired hormone secretion. Treatment, whether surgical or medical depends, on the tumor subtype and degree of compression; however, a significant proportion of patients do not achieve optimal control of mass effects or hormonal hypersecretion. Unraveling the pathogenesis of pituitary adenomas is a critical step in the quest for new subcellular treatment targets that will decrease morbidity and mortality related to these tumors. A large diversity of pathogenetic mechanisms has been described so far including deregulation of cell cycle, molecular pathways and angiogenesis. Major signaling pathways such as Notch, Wnt and Hedgehog, which are mainly active in the early phase of pituitary organogenesis and are essential for the development of somatotrophs, lactotrophs thyrotrophs and corticotrophs, have been implicated in the pathogenesis of pituitary adenomas. In this review we present novel data regarding the role of Notch and Hedgehog regulatory networks in pituitary development and pathogenesis of pituitary adenomas.