{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:47:55Z","timestamp":1791805675213,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01 DK134580"],"award-info":[{"award-number":["5R01 DK134580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Benign prostatic hyperplasia (BPH) is the most common disease in aging males. BPH growth is androgen\u2010dependent, and it appears that androgens preferentially stimulate the growth of BPH as compared to normal prostate. The mechanism of preferential androgen stimulation of BPH growth is not clear. Our previous studies suggest that primary BPH stromal cells, but not the paired normal adjacent prostate (NAP) stromal cells from the same patients, could stimulate prostatic epithelial cell proliferation in 3D co\u2010culture. However, whether androgen regulation of prostatic stromal cells is altered in BPH nodules is not clear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Paired BPH and NAP primary stromal cells were prepared from the same patients. Early passage paired BPH and NAP primary cells were treated with androgens and\/or antiandrogens for RNA\u2010seq analysis. RNA\u2010seq data were analyzed using principal component analysis (PCA) and functional enrichment analysis. Conditioned medium of the paired BPH and NAP primary cells in the presence or absence of androgens were used in three\u2010dimensional (3D) culture of benign prostatic epithelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RNA\u2010seq data analysis suggests that androgen\u2010induced gene expression in BPH primary stromal cells is heightened compared to paired NAP stromal cells. AR activation in BPH stromal cells appears to enhance cellular motility, vascular and extracellular matrix remodeling, and paracrine signaling, while simultaneously modulating cell cycle and metabolic processes. Compared to regular BPH stromal conditioned medium, conditioned medium of androgen\u2010stimulated BPH stromal cells further enhanced prostatic epithelial cell proliferation in 3D culture. In contrast, medium of NAP stromal cell culture conditioned in the presence of androgen had no significant effect on prostatic epithelial cell proliferation in 3D culture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that androgen stimulation of prostatic epithelial cell growth via paracrine prostatic stromal signaling is enhanced in BPH and is associated with heightened androgen\u2010responsiveness of BPH stromal cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70239","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:41:16Z","timestamp":1788115276000},"page":"1508-1517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Primary BPH Stromal Cell Cultures Exhibit Heightened Androgen\u2010Responsiveness"],"prefix":"10.1002","volume":"86","author":[{"given":"Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4714-7531","authenticated-orcid":false,"given":"Fulu","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5702-4036","authenticated-orcid":false,"given":"Mohammad Reza","family":"Askarpour","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-1662","authenticated-orcid":false,"given":"Laura E.","family":"Pascal","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"UPMC Hillman Cancer Center University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-6112","authenticated-orcid":false,"given":"Rajiv","family":"Dhir","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Chandran","sequence":"additional","affiliation":[{"name":"UPMC Hillman Cancer Center University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Department of Biomedical Informatics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce L.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7662-4886","authenticated-orcid":false,"given":"Donald B.","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8070-1664","authenticated-orcid":false,"given":"Naoki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-4767","authenticated-orcid":false,"given":"Zhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"},{"name":"UPMC Hillman Cancer Center University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990150506"},{"issue":"5","key":"e_1_2_9_3_1","first-page":"122","article-title":"BPH: Epidemiology and Comorbidities","volume":"12","author":"McVary K. 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