Pd11-11 the expression of estrogen receptors is associated with steroid 5-alpha reductase 2 in prostatic tissue

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD11)1 Sep 2021PD11-11 THE EXPRESSION OF ESTROGEN RECEPTORS IS ASSOCIATED WITH STEROID 5-ALPHA REDUCTASE 2 IN PROSTATIC TISSUE Christina Sharkey, Xingbo Long, Aria F. Olumi, and Zongwei Wang Christina SharkeyChristina Sharkey More articles by this author , Xingbo LongXingbo Long More articles by this author , Aria F. OlumiAria F. Olumi More articles by this author , and Zongwei WangZongwei Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001986.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is a highly prevalent health problem among elderly men. Steroid 5α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. However, patients respond very differently to 5α-reductase inhibitors (5ARIs). Our previous study demonstrated that there is an “androgenic to estrogenic switch” when SRD5A2 is absent in the prostate gland. Here we wished to identify if estrogen receptors (ER) expression is associated with SRD5A2 in the prostate. METHODS: 18 prostatic specimens collected from patients who underwent transurethral resection of the prostate were used to determine the transcript and protein expressions of ERα and ERβ. Mouse and human single-cell RNA sequencing (scRNA seq) data were analyzed to identify the subpopulation for ERα and ERβ expression. The expression of ERs was correlated to SRD5A2 expression with RNA sequencing (RNA seq) data from GTEx (Genotype-Tissue Expression, n=100) in normal prostate and TCGA (The Cancer Genome Atlas, n=496) databases for prostate cancer. Human prostatic stromal cell line (BHPrS1) and epithelial cell line (BPH1) were transfected with SRD5A2 plasmid or vector to identify the change of transcript and protein levels of SRD5A2, ERα, and ERβ. RESULTS: ERα and ERβ variably expressed in both the stroma and epithelium compartments of BPH surgical samples and had nucleus expression in human prostatic cell lines. ScRNA seq analysis of human and mouse prostate tissues showed that SRD5A2 dominantly expressed in fibroblasts. Meanwhile, ERα expressed mainly in myofibroblasts of human prostate and in luminal cells of mouse anterior prostate. ERβ had minimal expression both in mouse and human prostate. RNA seq analysis demonstrated that there was a significant association between SRD5A2 and ERα both in human benign and malignant prostate tissue. The transcript level of SRD5A2 was significantly positively correlated with ERα (R=0.6797, p=0.0019) and ERβ (R=0.7030, p=0.0011) in surgical specimens. In addition, in BHPrS1 cells, transcript and protein expressions of total ERα and phosphorylated ERα were upregulated in SRD5A2 overexpressed cells compared with vector control. CONCLUSIONS: Our study demonstrates that the expression of ERα is associated with SRD5A2 expression. Targeting the estrogenic signaling pathway may serve as an effective treatment strategy in 5ARI-insensitive BPH patients. Source of Funding: This study was supported by National Institutes of Health (NIH)/ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e202-e202 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina Sharkey More articles by this author Xingbo Long More articles by this author Aria F. Olumi More articles by this author Zongwei Wang More articles by this author Expand All Advertisement PDF downloadLoading ...