MP45-01 ANDROGENIC TO ESTROGENIC SWITCH IN THE PROSTATE GLAND OF OVERWEIGHT PATIENT

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2018MP45-01 ANDROGENIC TO ESTROGENIC SWITCH IN THE PROSTATE GLAND OF OVERWEIGHT PATIENT Zongwei Wang, Libing Hu, Shulin Wu, Shahin Tabetabaei, Chin-Lee Wu, and Aria Olumi Zongwei WangZongwei Wang More articles by this author , Libing HuLibing Hu More articles by this author , Shulin WuShulin Wu More articles by this author , Shahin TabetabaeiShahin Tabetabaei More articles by this author , Chin-Lee WuChin-Lee Wu More articles by this author , and Aria OlumiAria Olumi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1440AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The steroid 5-α reductase type 2 (SRD5A2) is critical for prostatic development and growth. Strategies to block SRD5A2 using 5-α reductase inhibitors (5ARI) remain a mainstay in the treatment of benign prostatic hyperplasia (BPH). However, one-third of men are resistant to 5ARI therapies. We previously showed that body mass index (BMI) correlates with increased SRD5A2 gene promoter methylation and decreased protein expression in men with symptomatic BPH. We have demonstrated that there is an androgenic to estrogenic switch when SRD5A2 is absent in the prostate gland. Here we wished to identify whether BMI is associated with the androgenic to estrogenic switch in human prostate tissue. METHODS Prostate specimens were collected from 35 patients who underwent transurethral resection of the prostate for symptomatic BPH at Massachusetts General Hospital. Medical records were reviewed to retrospectively collect clinical and pathological data. Patients were categorized by BMI as lean (less than 25 kg/m2), and overweight (25 kg/m2 or greater). Use and duration of α-blockers and/or 5ARIs was assessed. Methylation of SRD5A2 promoter was assessed using Methylated CpG Island Recovery Assay (MIRA). Prostatic levels of testosterone, dihydrotestosterone and estradiol were measured by HPLC-MS. RESULTS We found that BMI was significantly correlated with methylation of SRD5A2 gene promoter (p<0.05) and absence of SRD5A2 protein expression. Higher BMI was associated with higher prostatic estradiol levels (p<0.05). IIEF-5 score, International Index of Erectile Function Questionnaire score, was negatively associated with BMI (p<0.05). Treatment with 5ARIs dramatically increased the level of prostate testosterone levels and testosterone/estradiol ratio in the prostate specimens (p<0.01, p=0.01, respectively), and decreased the level of dihydrotestosterone (p<0.05). CONCLUSIONS Our study demonstrates for the first time that there is an androgenic to estrogenic switch in the prostate glands of overweight patients. Associated with body weight, somatic epigenetic silencing of SRD5A2 changes the prostatic hormonal milieu, and may modulate prostatic homeostasis and growth. Targeting the estrogenic signaling may serve as an effective treatment strategy in subset of overweight BPH patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e597 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Zongwei Wang More articles by this author Libing Hu More articles by this author Shulin Wu More articles by this author Shahin Tabetabaei More articles by this author Chin-Lee Wu More articles by this author Aria Olumi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...