Prolactinomas: Role of VEGF, FGF-2 and CD31

Abstract

Pituitary tumors rarely produce metastasis, but cause considerable morbidity and mortality. Each pituitary tumor of clonal origin represents the multifactorial result of failure of different regulatory events where growth and angiogenic factors may play critical roles in hormone secretion and cell proliferation. Prolactinomas, pituitary tumors which secrete prolactin, are generally treated successfully with dopamine agonists, even though a 10–15 % are resistant to this pharmacological therapy.The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive pituitary prolactinomas when compared to noninvasive prolactinomas. Furthermore, it has also been described that macroprolactinomas are more vascular than microprolactinomas.Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1 and PTTG, which give a particular vascular phenotype, are modified in pituitary adenomas. Inhibitors of angiogenesis, Thrombospondin-1 and FGF-2 endogenous antisense have also been detected. In particular, vascular endothelial growth factor (VEGF) the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression, and in particular, in dopamine resistant prolactinomas. Even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives.KeywordsVascular Endothelial Growth FactorPituitary AdenomaDopamine AgonistVascular Endothelial Growth Factor ReceptorPituitary TumorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.