1581 ESTROGEN RECEPTORS MEDIATE STROMAL-EPITHELIAL INTERACTIONS IN BPH

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20121581 ESTROGEN RECEPTORS MEDIATE STROMAL-EPITHELIAL INTERACTIONS IN BPH William Ricke and Emily Ricke William RickeWilliam Ricke Madison, WI More articles by this author and Emily RickeEmily Ricke Madison, WI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1353AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Benign prostatic hyperplasia (BPH) is highly prevalent among aging men and can result in bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS) that significantly impact health and quality of life. Currently the androgen receptor signaling cascade is a chief pathway targeted in the treatment of BPH. However, androgens can be metabolized to highly potent estrogens that may play an important role in the manifestation and progression of BPH and associated LUTS. The purpose of this project was to determine the stromal versus epithelial localization of estrogen receptors (ER) in normal prostate and BPH specimens of epithelial and mixed epithelial subtypes. Additionally we wanted to determine if proliferation of prostatic cells was affected by estrogens or selective estrogen receptor modulators in vitro. METHODS Detection and quantification of ERs in prostate specimens was performed using the Vectra analysis system, which provides an unbiased detection of chromogen and hence objective ER recognition in tissue specimens. RESULTS ER was detected in approximately 12% and 8.5% of total cells from benign (n=45) and BPH (n=25) specimens, respectively. The percentage of epithelial ER positive cells was significantly (P<0.05) increased in BPH compared to normal and the percentage of stromal ER positive cells was significantly (P<0.05) lower in BPH. Estradiol (E2) did not significantly affect proliferation of prostate stromal or epithelial cells directly when grown in culture, nor did E2 increase stromal cell proliferation when grown in E2 treated epithelial cell conditioned media. However, epithelial cell growth was significantly (P<0.05) increased when grown in E2 treated stromal cell conditioned media (OD= 0.39) vs untreated stromal cell conditioned media controls (OD= 0.25). Similar results were obtained in experiments where the antiestrogen, Raloxifene, was used. When epithelial cells were grown in Raloxifene treated stromal cell conditioned media, it significantly (P<0.05) decreased epithelial cell proliferation vs untreated stromal cell conditioned media (OD=0.21vs 0.33, respectively). CONCLUSIONS These data suggest that in BPH, ER localization changes according to tissue layer and hence ER regulated events are increasingly mediated via the epithelium. Interestingly, functional assays suggest that estrogen regulation of the stroma plays a key role in the overall proliferation during BPH. Generally, these data implicate the estrogen pathway as a potential therapeutic pathway in the treatment of BPH and associated LUTS. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e640 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information William Ricke Madison, WI More articles by this author Emily Ricke Madison, WI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...