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Estrogen Receptor-α is a Key Mediator and Therapeutic Target for Bladder Complications of Benign Prostatic Hyperplasia

2014; Lippincott Williams & Wilkins; Volume: 193; Issue: 2 Linguagem: Inglês

10.1016/j.juro.2014.08.093

1527-3792

Tristan M. Nicholson, Michael A. Moses, Kristen S. Uchtmann, Kimberly P. Keil, Dale E. Bjorling, Chad M. Vezina, Ronald W. Wood, William A. Ricke,

Urologic and reproductive health conditions

No AccessJournal of UrologyInvestigative Urology1 Feb 2015Estrogen Receptor-α is a Key Mediator and Therapeutic Target for Bladder Complications of Benign Prostatic Hyperplasia Tristan M. Nicholson, Michael A. Moses, Kristen S. Uchtmann, Kimberly P. Keil, Dale E. Bjorling, Chad M. Vezina, Ronald W. Wood, and William A. Ricke Tristan M. NicholsonTristan M. Nicholson Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin Medical Scientist Training Program, University of Wisconsin-Madison, Madison, Wisconsin Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York , Michael A. MosesMichael A. Moses Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York , Kristen S. UchtmannKristen S. Uchtmann Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin , Kimberly P. KeilKimberly P. Keil Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin , Dale E. BjorlingDale E. Bjorling Department of Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin , Chad M. VezinaChad M. Vezina Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin , Ronald W. WoodRonald W. Wood Department of Obstetrics and Gynecology and Urology, University of Rochester School of Medicine and Dentistry, Rochester, New York , and William A. RickeWilliam A. Ricke Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin View All Author Informationhttps://doi.org/10.1016/j.juro.2014.08.093AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Estrogens are important in prostate growth and have a role in benign prostatic hyperplasia. However, to our knowledge no current therapy directly targets estrogen action. Estrogens act primarily via estrogen receptors α and β. In a mouse model we evaluated the relative contribution of these receptors to bladder complications of benign prostatic hyperplasia. We also evaluated the prevention of these bladder complications using the selective estrogen receptor modulators raloxifene and tamoxifen (estrogen receptor-α selective antagonists), and R,R-THC (estrogen receptor-β selective antagonist). Materials and Methods: Adult male C57bl/6 mice received implants of 25 mg testosterone and 2.5 mg 17β-estradiol slow release pellets. Untreated controls underwent sham surgery. We evaluated the contributions of the estrogen receptor subtypes in ERαKO and ERβKO mice compared to their respective wild-type litter mates. Wild-type mice treated with testosterone plus 17β-estradiol were compared to mice treated with testosterone plus 17β-estradiol and 25 mg selective estrogen receptor modulators to evaluate the prevention of benign prostatic hyperplasia complications by selective estrogen receptor modulators. Results: Large bladders with urinary retention developed in ERαWT and ERβWT litter mates treated with testosterone plus 17β-estradiol but such bladders did not develop in ERαKO mice treated with testosterone plus 17β-estradiol. ERβKO mice treated with testosterone plus 17β-estradiol had large bladders with urinary retention and increased bladder mass. Cotreatment with the estrogen receptor-α antagonist raloxifene resulted in decreased bladder mass compared to that in wild-type mice treated with testosterone plus 17β-estradiol. Bladders in mice treated with the estrogen receptor-β antagonist R,R-THC were similar to those in testosterone plus 17β-estradiol treated mice. 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Volume 193Issue 2February 2015Page: 722-729 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Keywordsurinary bladderprostatic hyperplasialower urinary tract symptomstestosteroneestradiolAcknowledgmentsEmily Ricke, Tyler Bauman, Jonathan Ewald, Jalissa Wynder, Ashleigh Theberge, Pam Weller and Nikesha Haynes, University of Rochester Medical Center, provided animal collection assistance and manuscript feedback. Dr. Edward Messing, Department of Urology, University of Rochester, provided support.MetricsAuthor Information Tristan M. Nicholson Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin Medical Scientist Training Program, University of Wisconsin-Madison, Madison, Wisconsin Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York More articles by this author Michael A. Moses Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York More articles by this author Kristen S. Uchtmann Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin More articles by this author Kimberly P. Keil Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin More articles by this author Dale E. Bjorling Department of Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin More articles by this author Chad M. Vezina Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin More articles by this author Ronald W. Wood Department of Obstetrics and Gynecology and Urology, University of Rochester School of Medicine and Dentistry, Rochester, New York More articles by this author William A. Ricke Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin More articles by this author Expand All Advertisement PDF downloadLoading ...