Signaling pathways regulating pituitary lactotrope homeostasis and tumorigenesis

Dysregulation of the signaling pathways that govern lactotrope biology contributes to tumorigenesis of prolactin (PRL)-secreting adenomas, or prolactinomas, leading to a state of pathological hyperprolactinemia. Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor. In this review, we highlight signaling pathways involved in lactotrope development, homeostasis, and physiology of pregnancy, as well as implications for signaling pathways in pathophysiology of prolactinoma. We also review mutations found in human prolactinoma and briefly discuss animal models that are useful in studying pituitary adenoma, many of which emphasize the fact that alterations in signaling pathways are common in prolactinomas. Although individual mutations have been proposed as possible driving forces for prolactinoma tumorigenesis in humans, no single mutation has been clinically identified as a causative factor for the majority of prolactinomas. A better understanding of lactotrope-specific responses to intracellular signaling pathways is needed to explain the mechanism of tumorigenesis in prolactinoma.