Estrogens have previously been extensively used in
prostate cancer treatment. Serious side effects, primarily in cardiovascular system have, however, limited their use. The
therapeutic effect of
estrogen in preventing
prostate cancer growth was mainly obtained indirectly by feedback inhibition of the hypothalamic release of LRH leading to lowered serum
androgen levels and
castration like effects. Prostate tissue is also most probably a target for direct regulation by
estrogens. Prostate contains
estrogen receptor alpha (
ERalpha) and beta (
ERbeta), which are localized characteristically in stroma and epithelium, respectively. The physiological function of these receptors is not known but there is evidence of the role of
estrogens in prostatic
carcinogenesis. Developing prostate seems particularly sensitive to increased level of endogenous and/or exogenous
estrogens. Perinatal or neonatal exposure of rats and mice to
estrogens leads to "imprinting" of prostate associated with increased proliferation,
inflammation and dysplastic epithelial changes later in life. Prolonged treatment of adult rodents with
estrogens along with
androgens also leads to epithelial
metaplasia, PIN-like lesions and even
adenocarcinoma of prostate speaking for the role of
estrogen in
prostate cancer development. Recent results concerning
antiestrogen inhibition of
prostate cancer development beyond PIN-type lesions in transgenic mouse models further suggests a role for
estrogens in
prostate cancer progression. These results also suggest that direct inhibition of
estrogen action at the level of prostate tissue may provide an important novel principle of development of
prostate cancer therapies.