Both androgens and estrogens play a significant role in the prostate and are critical for normal prostate growth and development. The role of androgens in the prostate and in prostate disease is well known, however, the role for estrogens in the prostate and in prostate disease is complex and is still only just beginning to be appreciated. Our understanding of the role and action of estrogens in the prostate has advanced significantly recently due to important discoveries, including the discovery of a second estrogen receptor subtype (ER-beta), the detection of aromatase in the prostate, and the identification of rapid nongenomic estrogen signaling. We now know that estrogens are essential for normal tissue homeostasis within the prostate and that too little or too much leads to perturbation of the glands growth and the emergence of disease. We are also beginning to recognize the importance and differential roles of the estrogen receptors ER-alpha and ER-beta. Specifically, the activation of ER-alpha leads to aberrant proliferation, inflammation, and the development of premalignant lesions, while, in contrast, the activation of ER-beta is critical in prostatic stromal-epithelial cell signaling and mediating antiproliferative effects that balance the proliferative action of androgens on the epithelia. These data have established the importance and complexity of estrogen action. We now know that estrogens have the capacity to exert both beneficial and adverse effects in the prostate via ER-beta and ER-alpha, respectively. Based on this, the selective targeting of estrogen action may form the basis of new therapies for prostate disease.

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Tissue-specific aromatase production is significant in breast cancer and osteoporosis. Prostatic aromatase expression has been equivocal, and any local actions of estrogens are considered secondary to centrally mediated androgen suppression. We examine local aromatase expression and estrogen biosynthesis in the human prostate. Pure samples of stroma and epithelia from biopsy tissues were isolated by laser capture microdissection. Aromatase protein was detected by Western blot analysis, mRNA by RT-PCR, and enzyme activity by tritiated water assay, whereas promoter use was examined by real-time PCR. In nonmalignant prostate tissues, aromatase mRNA expression was absent from epithelium, but did localize to stroma. Presence of protein was confirmed, and expression was driven by promoter PII. Aromatase was expressed and active in LNCaP, PC3, and DU145 cells in addition to microdissected epithelial tumor cells; benign prostate epithelial cells showed no expression or activity. Promoter use in LNCaP and microdissected tumor cells was via PII, whereas PC3 and DU145 cells used promoter I.4. This study demonstrates local estrogen biosynthesis in prostate-induced aromatase gene expression in malignancy and potential alteration of aromatase promoter use with disease progression. These data provide a basis for continued investigation of local estrogen production and its potential role in prostate disease.