Early-life estrogens and prostate cancer in an animal model

While early-life estrogens are thought to play a physiologic role in prostate gland development, inappropriate estrogenic exposures either in dose, type or temporally can reprogram the prostate gland and increase susceptibility to abnormal prostate growth with aging including carcinogenesis. This review discusses the evidence for developmental estrogenic reprogramming that leads to adult prostate disease in a rat model. We propose that estrogen imprinting of the prostate is mediated through both structural reorganization of the gland early in life and epigenomic reprogramming that permits life-long memory of the inappropriate developmental exposures including heightened sensitivity to rising estradiol levels with aging. Complex interactions between early epigenetic programming and later-life experiences results in an emergence of multiple epigenomic outcomes, with some contributing to carcinogenesis with aging.