Estrogens and prostate cancer: from biosynthesis to physiological effects

Although the most impressive characteristic of prostate cancer is its androgen dependence, several studies support that 17β-estradiol (E₂) also play an important role in onset and progression of prostate cancer. Regarding the effects of E₂ in prostate carcinogenesis, we can highlight the carcinogenic properties of several products derived from E₂ metabolism, which play an important role on cell malignant transformation. Several polymorphisms in estrogen-related genes such as estrogen receptors (ERs) and enzymes involved in E₂ biosynthesis and metabolism have been described to favour carcinogenesis. Also, both isoforms of ERs (ERα and ERβ), which act on cells in order to maintain the normal physiology of prostate gland, are differentially expressed between neoplastic and non-neoplastic prostate cells. Therefore, this deregulation may conduct to alterations on normal gene expression in prostate cells, which may favour the progression and migration of cancer cells. On the other hand, other studies have been pointing the anti-carcinogenic activity of E₂ in prostate. These contradictory effects are based on the role of ERβ, which has been shown to exhibit anti-proliferative and anti-oxidant functions. Taking into account the scientific evidences that relate E₂ with prostate cancer, several therapeutic approaches based on ERs are being explored. This chapter summarizes the main knowledge on how E₂ may contribute to the pathophysiology of prostate gland.