Background: Many studies demonstrate that growth factors play an important role in the pathogenesis of prolactinoma induced by estrogen. The effects of estrogen are mainly mediated through its nuclear receptor (ER alpha); however, expression of ER alpha and growth factors in prolactinoma and healthy pituitary and their relationship remain obscure. Aim: To obtain new insights regarding the expression differences of these factors and their relationship and to investigate the correlation between gender and clinical features in patients with prolactinoma. Subjects and methods: A total of 21 human prolactinomas and 6 healthy human pituitaries were examined for mRNA expression of ER alpha, basic fibroblast growth factor (bFGF), transforming growth factor alpha (TGF alpha), TGF beta 1, TGF beta 3, and TGF beta receptor type II (TGF beta RII) by means of real-time PCR. Patient clinical data was also analyzed. Results: Both PRL level and tumor volume of the male patient group were higher than that of the female patient group. There was a significant correlation between PRL level and tumor volume in the total patient group. Expression of ER alpha, bFGF, TGF alpha, and TGF beta 3 mRNA levels of the patient group were significantly different from that of the control group. A significant correlation between ER alpha mRNA levels and PRL levels, tumor volume, TGF beta 1 mRNA levels in the total patient group were found. Conclusions: PRL level and tumor volume have a significant difference between genders in prolactinoma patients. ER alpha and some growth factors may be involved in the tumorigenesis of prolactinoma. ER alpha could potentially be an effective therapy target for treating prolactinoma. (J. Endocrinol. Invest. 35: 174-180, 2012) (C) 2012, Editrice Kurtis