MP36-15 EFFECTS OF DUTASTERIDE ON PROSTATIC INFLAMMATION MEDIATED BY ESTROGEN RECEPTOR β IN A RAT MODEL OF NONBACTERIAL PROSTATITIS

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II1 Apr 2016MP36-15 EFFECTS OF DUTASTERIDE ON PROSTATIC INFLAMMATION MEDIATED BY ESTROGEN RECEPTOR β IN A RAT MODEL OF NONBACTERIAL PROSTATITIS Shinsuke Mizoguchi, Kenichi Mori, Fuminori Sato, Naoki yoshimura, and Hiromitsu Mimata Shinsuke MizoguchiShinsuke Mizoguchi More articles by this author , Kenichi MoriKenichi Mori More articles by this author , Fuminori SatoFuminori Sato More articles by this author , Naoki yoshimuraNaoki yoshimura More articles by this author , and Hiromitsu MimataHiromitsu Mimata More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1649AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Estrogen receptor β (ERβ) stimulation can improve local inflammation whereas ERα stimulation could induce local inflammation. It has been reported that dutasteride, which not only inhibits 5α-reductase, but also stimulates ERβ, might have anti-inflammatory effects in the prostate of patients with lower urinary tract symptoms (Am J Mens Health September 7, 2015 doi:10.1177/1557988315604019). Therefore we investigated the effect of dutasteride on prostatic inflammation using a rat model of nonbacterial prostatitis. METHODS Male SD rats at 10 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (CG, n=5). Rats with prostatitis were divided into dutasteride therapy (TG, n=5) and placebo groups (PG, n=5). TG rats were treated with dutasteride at a dose of 0.5mg/kg daily from 2 days before induction of prostatitis whereas PG rats received vehicle only. Twenty-eight days later, conscious cystometry was performed to measure non-voiding contractions (NVCs), voiding interval (VI) and postvoid residual volume (RV). After cystometry, the prostate was excised for analysis of mRNA expression levels of ERα, ERβ, IL1B, IL18 by real-time PCR. RESULTS The mean number of NVCs was significantly greater in PG rats than that of CG rats (P<0.05), and VI were significantly decreased in PG rats compared to CG rats (P<0.05), but not significantly different between CG and TG rats. There was no significant difference in RV among groups. mRNA expression of ERα, IL1B and IL18 were significantly increased in PG rats compared to CG rats (P<0.05), but not significantly different between CG and TG rats. On the other hand, mRNA expression level of ERβ was significantly decreased in PG rats compared to CG rats (P<0.05), but not significantly different between CG and TG rats. The relative mRNA expression ratio of ERβ against ERα (ERβ/ERα) in PG rats was significantly decreased compared to CG rats (P<0.05), whereas ERβ/ERα ratio in TG rats was significantly increased compared to PG rats (P<0.05). CONCLUSIONS Dutasteride improved not only prostatic inflammation evidenced by the decrease of mRNA IL1B and IL18 levels, which are reported as nonbacterial prostatitis markers, but also bladder overactivity as shown by cystmetric investigation. These therapeutic effects were associated with the increased ERβ/ERα ratio. Therefore, dutasteride might be effective via ERβ for the treatment of nonbacterial prostatic inflammation in addition to benign prostatic hyperplasia. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e495 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Shinsuke Mizoguchi More articles by this author Kenichi Mori More articles by this author Fuminori Sato More articles by this author Naoki yoshimura More articles by this author Hiromitsu Mimata More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...