Essential role for estrogen receptor beta in stromal-epithelial regulation of prostatic hyperplasia.

Estrogens, acting via estrogen receptors (ER) α and β, exert direct and indirect actions on prostate growth and differentiation. Previous studies using animal models to determine the role of ERβ in the prostate have been problematic because the centrally mediated response to estrogen results in reduced androgen levels and prostatic epithelial regression, potentially masking any direct effects via ERβ. This study overcomes this problem by using the estrogen-deficient aromatase knockout mouse and tissue recombination to provide new insight into estrogen action on prostate growth and pathology. Homo- and heterotypic aromatase knockout tissue recombinants revealed stromal aromatase deficiency induced hyperplasia in normal prostatic epithelium due to disruption of paracrine interaction between stroma and epithelia. Treatment of tissue recombinants with an ERβ-specific agonist demonstrated that stimulation of ERβ elicits antiproliferative responses in epithelium that are not influenced by alterations to systemi...