Transforming growth factor-beta regulation of estradiol-induced prolactinomas

Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans, and increased tumor growth under estrogenic influence in female patients is often of clinical concern. Extensive experimental work has uncovered the roles of estrogen receptors and various growth-regulatory peptides in estradiol action on lactotropes. However, it is only recently that we are beginning to gain insight into how these growth factors interact to regulate estradiol action on lactotrope cell proliferation. Recent studies have identified the regulatory role of TGF-beta-related peptides in estradiol action on lactotropes. Additionally, these studies determined that TGF-beta and FGF interact to facilitate the communication between lactotropes and folliculostellate cells that is necessary for the mitogenic action of estradiol. This review addresses the role of estradiol in prolactinoma formation and summarizes data that support a novel concept: Alterations in the expression and action of TGF-beta isoforms are crucial steps in estradiol-induced tumorigenesis.