NEONATAL ESTROGEN EXPOSURE UP-REGULATES ESTROGEN-RECEPTOR EXPRESSION IN THE DEVELOPING AND ADULT-RAT PROSTATE LOBES

Neonatal exposure to estrogens results in permanent imprints of the ra t prostate gland. To delineate the direct target of estrogen action wi thin that tissue, the present study examined estrogen receptor (ER) ex pression by immunocytochemistry and in situ hybridization. ER were con fined to mesenchymal cells in the urogenital sinus and proximal region s of the budding prostate lobes of newborn control rat prostates, and this expression declined after morphogenesis. Exposure to estradiol be nzoate on days 1, 3, and 5 resulted in indiction of ER expression in p eriductal smooth muscle cells from the proximal regions out to the dis tal tips of the developing prostate lobes. This ER expression was asso ciated with the appearance of ER messenger RNA in those cells; thus, i t was concluded that the up-regulation of ER by estrogens is mediated at the message level. Autoregulation of ER expression was next examine d in adult prostates that had been exposed to oil or estrogens neonata lly. Day 70 rats were castrated and given testosterone with or without estradiol for 7 days before death. Estrogen exposure in adulthood ind uced low levels of epithelial cell ER in the lateral lobe. Neonatal es trogenization increased the sensitivity of lateral lobe epithelial cel ls to this autoregulation, as the incidence and intensity of ER immuno staining were markedly increased. No autoinduction of ER was observed in adult ventral or dorsal prostatic lobes. From the present study we conclude that smooth muscle cells are the targets of estrogen action i n the developmentally estrogenized prostate and that estrogen amplifie s its own effects through auto-up-regulation of ER. In addition, later al lobe epithelial cells are sensitive to estrogen up-regulation of ER , which may in part account for the lobe-specific effects observed aft er neonatal estrogenization of the prostate gland.