PD16-08 ALTERNATE ANDROGEN-INDEPENDENT ESTROGEN SIGNALING FOR PROSTATIC GROWTH

Abstract

You have accessJournal of UrologyCME1 May 2022PD16-08 ALTERNATE ANDROGEN-INDEPENDENT ESTROGEN SIGNALING FOR PROSTATIC GROWTH Christina Sharkey, Xingbo Long, Ra'ad Al-Faouri, Zongwei Wang, and Aria F. Olumi Christina SharkeyChristina Sharkey More articles by this author , Xingbo LongXingbo Long More articles by this author , Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Zongwei WangZongwei Wang More articles by this author , and Aria F. OlumiAria F. Olumi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002548.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Steroid 5α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. SRD5A2 inhibitors (5ARI) are the only class of benign prostate hyperplasia-related medications that reduce prostate size. However, the progression of lower urinary tract symptoms (LUTS) associated with BPH was only slowed by 34% in those treated with 5ARI. Through epigenetic regulation, we have shown that one-third of adult patients lack expression of prostatic SRD5A2. Here we wished to identify the subpopulation of prostate cells resistant to 5ARI therapy and determine alternative non-androgenic pathways that contribute to prostate growth in the absence of SRD5A2. METHODS: Single prostatic cells of homozygous SRD5A2-/- mice and littermate heterozygous SRD5A2+/- control mice were isolated and processed using the 10x genomics platform for single cell RNA-sequencing (scRNA-seq). A complete transcriptomic profile was obtained to identify cellular subsets and functional differentiation. Specific cell clusters were validated in situ using immunohistochemistry and RNA in situ hybridization. Levels of transcription factors were tested by qPCR. RESULTS: Analysis of transcriptome data for 23,000 single cells revealed 16 subpopulations. Luminal epithelial cells (LE) were further identified as five clusters. In SRD5A2-/- mice, while the total number of LE cells decreased, the percentage of LE2 subcluster increased. LE2, a predominant high expressor of estrogen receptor alpha (ESR1), was predominately located in the anterior prostate with enriched gene ontology (GO) terms of Wnt and MAPK signaling pathways. Zfp143, the transcription factor of ESR1, was dramatically upregulated in the absence of SRD5A2. CONCLUSIONS: Our data demonstrate the heterogeneity of cell populations within the mouse prostate. LE2, with an enhanced estrogen response gene signature, may play an important role in alternative pathways for prostate growth in the absence of SRD5A2. Understanding the underlying androgen-independent pathways contributing to prostate growth can help identify novel therapeutic targets for the management of prostatic diseases. Source of Funding: National Institutes of Health (NIH)/ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH/R01 DK124502) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e271 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina Sharkey More articles by this author Xingbo Long More articles by this author Ra'ad Al-Faouri More articles by this author Zongwei Wang More articles by this author Aria F. Olumi More articles by this author Expand All Advertisement PDF DownloadLoading ...