Developmental estrogenization: Prostate gland reprogramming leads to increased disease risk with aging

Abstract

While estrogens are involved in normal prostate morphogenesis and function, inappropriate early-life estrogenic exposures, either in type, dose or timing, can reprogram the prostate gland and lead to increased disease risk with aging. This process is referred to as estrogen imprinting or developmental estrogenization of the prostate gland. The present review discusses published and new evidence for prostatic developmental estrogenization that includes extensive research in rodent models combined with epidemiology findings that together have helped to uncover the architectural and molecular underpinnings that promote this phenotype. Complex interactions between steroid receptors, developmental morphoregulatory factors, epigenetic machinery and stem-progenitor cell targets coalesce to hard wire structural, cellular and epigenomic reorganization of the tissue which retains a life-long memory of early-life estrogens, ultimately predisposing the gland to prostatitis, hyperplasia and carcinogenesis with aging.

Keywords: Development; Estrogen; Estrogenization; HOXB13; Prostate; Reprogramming.