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International Journal of Endocrinology
Volume 2014, Article ID 608497, 11 pages
Review Article

Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models

1Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
2CITNOBA (CONICET-UNNOBA), Universidad Nacional del Noroeste de la Provincia de Buenos Aires, Monteagudo 2772, Pergamino, 2700 Buenos Aires, Argentina
3Servicio de Neurocirugía, Clínica Santa Isabel, Avenida Directorio 2037, C1406GZJ Buenos Aires, Argentina
4Servicio de Neurocirugía, Hospital Santa Lucía, Avenida San Juan 2021, C1232AAC Buenos Aires, Argentina

Received 16 June 2014; Accepted 30 October 2014; Published 18 November 2014

Academic Editor: Daizo Yoshida

Copyright © 2014 Carolina Cristina et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 or macropituitary prolactinomas when compared to noninvasive and 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 human and experimental pituitary adenomas of different histotypes. 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, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, 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.