Recently evidence has been accumulating that important abnormalities in the receptor status and postreceptor signal transduction frequently occurred in human pituitary tumors. Several in vivo and in vitro studies suggest that during tumoral expansion, pituitary cells acquire functionally active receptors and respond to a variety of hypothalamic hormones. Alterations in proteins responsible for signal transduction have been reported. Somatic mutations of the alpha chain of Gs, the stimulatory regulatory protein of adenylate cyclase (AC), causing constitutive activation of AC have been identified in a subset of human GH-secreting adenomas. Alterations in receptor and signal transduction mechanisms in pituitary tumors triggered by hypothalamic hormones may result in amplification of stimulatory inputs and impairment of inhibitory inputs.