Aromatase P450 expression in human pituitary adenomas

Estrogen has been shown to play an important role in pituitary tumor pathogenesis. In humans, this biosynthesis is mediated by aromatase, an enzyme that converts androgens to estrogens. Just a few studies about aromatase expression in human pituitary gland, both in normal and pathological ones, are found in the literature. This study aimed to assess aromatase enzyme expression in human pituitary adenomas and associate it with gender, tumor size and tumor subtype. We conducted a cross-sectional study, reviewed clinical data and surgical specimens of consecutive 65 patients (35 women and 30 men) with anatomopathologic diagnosis of pituitary adenoma who underwent adenomectomy at a neurosurgical referral center in southern Brazil. Immunohistochemistry was performed to assess aromatase expression and define tumor subtype, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to estimate aromatase gene expression. Mean patient age was 45.6 (±13.3) years (range, 18 to 73 years), 86.2% of our samples were macroadenomas while 13.8% were classified as microadenomas. Based on clinical and immunohistochemical data, 23 (35.4%) patients had non-functioning adenomas, 19 (29.2%) had somatotroph adenomas (acromegaly), 12 (18.5%) had lactotroph adenomas (hyperprolactinemic syndrome), and 11 (16.9%) had corticotroph adenomas (Cushing's disease). Immunohistochemical analysis was performed in 59 cases, and 58 (98.3%) showed no aromatase expression. Quantification by qRT-PCR was performed in 43 samples, and 36 (83.7%) revealed no gene expression. Among tumor specimens examined by both techniques (37 cases), 30 showed no gene or protein expression (concordance index, 0.81). It is possible to mention that aromatase expression was lost in most pituitary adenomas, regardless of gender, tumor subtype, or tumor size.