The aim of this study was to investigate the functional role of estrogen receptor alpha (ER alpha) in MMQ pituitary prolactinoma cells in the absence of estrogen with respect to proliferation, prolactin (PRL) secretion, and expression of growth factors. MMQ cells were treated with the ERa antagonist fulvestrant, then proliferation and PRL secretion were measured using MTS and enzyme-linked immunosorbent assays. Levels of ER alpha, vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and B cell leukemia/lymphoma-2 (BCL-2) were measured using quantitative polymerase chain reaction and western blot analysis. Fulvestrant acted as a potent inhibitor of ER alpha expression, and significantly inhibited cell proliferation (by up to 57.6 +/- 2.2%) and PRL secretion (by up to 81.0%). Fulvestrant also significantly altered the expression levels of VEGF, MMP-9 and BCL-2. We conclude that ER alpha plays an important functional role in pituitary prolactinomas and is also involved in the expression of particular growth factors, even in the absence of estrogen. Fulvestrant treatment may be an effective therapy for such tumors. (C) 2011 Elsevier Ltd. All rights reserved.