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Estrogen exposure and estrogen regulation have been implicated in a variety of disease processes, with estrogen receptor (ER)\u2010\u03b1 pathways associated with disease progression and ER\u03b2 pathways considered to be disease\u2010protective through enhanced apoptosis and reduced cellular proliferation. Preclinical models of LUTS\/BPH have shown that ER\u03b1 activation contributes to disease initiation and progression. Self\u2010identified African American (AA) men have a high incidence of LUTS\/BPH, with increased incidence of non\u2010surgical treatment failure, larger prostates at time of surgery, and surgery occurring at a younger age compared with self\u2010identified European American (EA) men. While circulating estrogen levels are higher in AA individuals, regulation of ERs, particularly ER\u03b2, in normal and LUTS\/BPH human prostate has not been well characterized. In this study, we examined differences in ER expression between peripheral zone (PZ) and transition zone (TZ) prostate tissues using multiplex, multispectral imaging. Additionally, we assessed changes in ERs and steroid metabolism genes involved in ER\u03b2 signaling between normal and LUTS\/BPH prostate samples. Our study revealed underlying differences in steroid metabolism gene expression between normal AA and EA prostates, which were further altered with LUTS\/BPH. Importantly, the contribution of ER\u03b1 to LUTS\/BPH was more pronounced in EA prostate samples, whereas AA prostate samples exhibited an overall increase in the expression of both ER and estrogen metabolism\u2010related genes. Although estrogens have also been implicated in collagen deposition in the prostate of LUTS\/BPH patients, we did not observe significant differences in collagen deposition between AA and EA samples. These results suggest that racial differences in steroid hormone signaling pathways within the benign prostate represent a promising area for the development of precision\u2010based therapies to reduce LUTS in aging men. \u00a9 2025 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70000","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T05:29:26Z","timestamp":1764480566000},"page":"176-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estrogen regulation in the prostate underlies racial disparity in men with benign prostatic hyperplasia"],"prefix":"10.1002","volume":"268","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0879-2394","authenticated-orcid":false,"given":"Teresa T","family":"Liu","sequence":"first","affiliation":[{"name":"Wegmans School of Pharmacy, St. John Fisher University  Rochester NY USA"},{"name":"Department of Urology, George M. 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O'Brien Center of Research Excellence University of Wisconsin\u2013Madison  Madison WI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajiv","family":"Dhir","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-927X","authenticated-orcid":false,"given":"Douglas W","family":"Strand","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Southwestern  Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald B","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-2090","authenticated-orcid":false,"given":"William A","family":"Ricke","sequence":"additional","affiliation":[{"name":"Department of Urology, George M. 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