Evidence that epithelial and mesenchymal estrogen receptor-alpha mediates effects of estrogen on prostatic epithelium

In combination with androgens, estrogens can induce aberrant growth and mal ignancy of the prostate gland. Estrogen action is mediated through two rece ptor subtypes: estrogen receptors alpha (ER alpha) and beta (ER beta). Wild -type (wt) and transgenic mice lacking a functional ER alpha (alpha ERKO) o r ER beta (beta ERKO) were treated with the synthetic estrogen diethylstilb estrol (DES). DES induced prostatic squamous metaplasia (SQM) in wt and bet a ERKO but not in alpha ERKO mice, indicating an essential role for ER alph a, but not ERP, in the induction of SQM of prostatic epithelium. In order t o determine the respective roles of epithelial and stromal ER alpha in this response, the following tissue recombinants were constructed with prostati c epithelia (E) and stroma (S) from wt and ERKO mice: wt-S+wt-E, alpha ERKO -S+alpha ERKO-E, wt-S+alpha ERKO-E, and (alpha ERKO-S+wt-E. A metaplastic r esponse to DES was observed in wt-St-wt-E tissue recombinants. This respons e to DES involved multilayering of basal epithelial cells, expression of cy tokeratin 10, and up-regulation of the progesterone receptor. Tissue recomb inants containing (alpha ERKO-E and/or -S (alpha ERKO-S+alpha ERKO-E, wt-Salpha ERKO-E, and alpha ERKO-S+wt-E) failed to respond to DES. Therefore, f ull and uniform epithelial SQM requires ER alpha in the epithelium and stro ma. These results provide a novel insight into the cell-cell interactions m ediating estrogen action in the prostate via ER alpha. (C) 2001 Academic Pr ess.