Aromatase and prostate cancer.

The normal growth and development of the prostate requires the presence and action of androgens, which are also known risk factors in the origins of benign and malignant prostate disease. Paradoxically, the incidence of prostate disease increases with age when serum androgen levels are in decline and emerging evidence suggests that estrogens may also be important in the normal prostate, as well as in the etiology of prostate disease. Both estrogen receptor subtypes are present in the prostate, demonstrating that the gland responds directly to estrogens. Recent data suggests that estrogens play a role in prostate disease and has demonstrated that high doses of estrogens induce premalignant dysplasia and in combination with high doses of androgens, malignancy. The production of estrogens from androgens is mediated by the aromatase enzyme, the aberrant expression of which plays a critical role in the disease process in other tissues, most notably the breast. The prostate expresses aromatase within the stroma of benign tissue, while in malignancy there is an induction of epithelial expression with altered promoter utilisation. Although the presence of aromatase in the prostate and its aberrant expression in prostate cancer is significant, its role and contribution to prostate carcinogenesis remains unclear. Transgenic mouse models lacking aromatase (ArKO) and over-expressing aromatase (AROM+) have provided an ideal means to examine aromatase expression in the prostate. Studies using these animals may lead to a better understanding of the role that aromatase--and therefore estrogen--plays in the development and progression of prostate disease.