Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship to tumor behavior

Abstract

The aim of the study was to evaluate the presence of aromatase cytochrome P450 enzyme (P450AROM) expression in normal pituitary tissues and tumor tissues of patients with prolactinoma and to examine the impact of the P450AROM expression on clinical outcome. Twenty-six consecutive human pituitary tissue samples were obtained from autopsies performed at the Institute of Forensic Medicine. Sixty-four patients who had an adenomectomy between 2000 and 2009 after prolactinoma diagnosis with histologically confirmed pituitary tumor tissues were retrospectively included in this study. The slices from the pituitary tissues were subjected to immunohistochemical staining for evaluation of P450AROM and estrogen receptor beta (ER beta) subunit. Immunohistochemistry results were compared according to age, gender, remission rate, resistance and invasion status of the patients. Higher than normal P450AROM expression was found in the pituitary tissues of the patients with prolactinoma (p < 0.001). P450AROM intensity had no relation to resistance or remission in patients with prolactinoma (p = 0.44, p = 0.45, respectively). The subgroup analysis showed that compared to males without invasive adenoma, males with invasive adenoma had higher P450AROM expression (p = 0.048). ER beta was found to have an impact on resistance (p = 0.049). This study shows that P450AROM expression is present in the pituitary tissues of patients with prolactinoma and that this presence could be important in development and tumor behavior of prolactinomas.

Aromatase enzyme expression in acromegaly and its possible relationship with disease prognosis

“…Similarly, in the study of Akıncı et al, ER-beta expression was seen higher in controls and invasive adenomas than noninvasive adenomas, although the difference was not statistically significant [4]. In addition, the relationship between aromatase and ER-beta expression was negatively directed but not statistically significant [4]. We observed a significant negative correlation between aromatase and ERalpha expression.…”

“…In contrast to aromatase expression, ERalpha expression was lower in the acromegaly group than in normal pituitary tissue. The role of local aromatization in prolactinoma has recently been shown by Akıncı et al In his study, aromatase expression was found to be higher in prolactinomas than in normal pituitary tissue, particularly in males with invasive adenoma, but no significant relationships were detected among p53, Ki-67, remission status, and aromatase expression [4]. Moreover, aromatase expression has also been observed in females with prolactinomas [26].…”

“…Many different cell types have been shown to express aromatase, including neurons, preadipocytes, fibroblasts, and gonadal cells, suggesting local estrogen synthesis by these cells [1][2][3]. The local conversion of testosterone to estrogen is important in normal physiology as well as in estrogen-induced tumor formation [4]. After discovery of the aromatase expression in the brain, the significance of local estrogen production in the regulation of reproductive process, sexual behavior, cognition, and recovery from neuronal injury have been shown in several studies [5][6][7].…”

“…Testosterone replacement has been also shown to elevate prolactin levels and to cause tumor growth in patients with prolactinoma [12]. After this growing evidence, aromatase expression has been observed in human prolactinoma tissues and suggested to affect tumor behavior [4]. In a recent study, treatment of male rat pituitary prolactin-producing cells in vivo with aromatase inhibitor and testosterone has shown the regulatory effect of aromatase on pituitary functions [13].…”

Local Transformations of Androgens into Estradiol by Aromatase P450 Is Involved in the Regulation of Prolactin and the Proliferation of Pituitary Prolactin-Positive Cells

“…Moreover, we reported a very strong correlation between the pituitary expression of aromatase and the incidence of spontaneous prolactinomas in old rats [3] and humans [4]. Similar results were later reported by different authors in non-tumoral pituitaries of humans and different animal species [5]–[11] and in human prolactinomas [12]. However, the physiological relevance of aromatase and the possible aromatization of testosterone to estradiol in the regulation of pituitary hormones are not well known.…”