{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T06:38:20Z","timestamp":1789799900308,"version":"4.0.1"},"reference-count":86,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>While dihydrotestosterone (DHT) has traditionally been considered the principal steroid in benign prostatic hyperplasia (BPH) pathogenesis, the role of estradiol (E2) and its relationship with local androgen accumulation remain unclear. This study investigated whether transition zone (TZ) tissue concentrations of E2, testosterone, and DHT are associated with prostate enlargement. TZ tissue cores were collected from 80 men undergoing prostate biopsy. Patients were stratified by total prostate volume (TPV): small (&lt;30 mL) and enlarged (\u226530 mL) prostate groups. Steroids were quantified using liquid chromatography-high resolution mass spectrometry. Tissue concentrations of E2, testosterone, and DHT were significantly higher in enlarged prostates (E2: 0.031 vs. 0.012 ng\/g; testosterone: 0.804 vs. 0.517 ng\/g; DHT: 7.903 vs. 3.526 ng\/g; all p &lt; 0.05). Across the cohort, TPV strongly correlated with DHT (R = 0.870, p &lt; 0.001), E2 (R = 0.845, p &lt; 0.001), and testosterone (R = 0.817, p &lt; 0.001). These findings demonstrate a strong association between local steroid accumulation and prostate enlargement, supporting the hypothesis that coordinated androgenic and estrogenic activity shapes the hormonal microenvironment driving BPH progression. This pattern aligns with a model of local steroidal hyperfunction that may amplify stromal\u2013epithelial signaling in the enlarged prostate.<\/jats:p>","DOI":"10.3390\/ijms27156785","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"6785","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated Estradiol and DHT Levels in the Prostatic Stroma as Key Drivers of Benign Prostatic Hyperplasia Pathogenesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Tomislav","family":"Pej\u010di\u0107","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, dr Suboti\u0107a 8, 11000 Belgrade, Serbia"},{"name":"Clinic of Urology, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4235-3504","authenticated-orcid":false,"given":"Milka","family":"Jadranin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Belgrade\u2014Institute of Chemistry, Technology and Metallurgy, Njego\u0161eva 12, 11158 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4406-8376","authenticated-orcid":false,"given":"Sini\u0161a","family":"\u0110ura\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, Studentski trg 12\u201316, 11158 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0989-7398","authenticated-orcid":false,"given":"Milica","family":"Kalaba","sequence":"additional","affiliation":[{"name":"Institute of General and Physical Chemistry, Studentski trg 12\u201316, 11158 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Doj\u010dinovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Belgrade\u2014Institute of Chemistry, Technology and Metallurgy, Njego\u0161eva 12, 11158 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2597-3426","authenticated-orcid":false,"given":"Milica","family":"Zekovi\u0107","sequence":"additional","affiliation":[{"name":"Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Tadeu\u0161a Ko\u0161\u0107u\u0161ka 1, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-2745","authenticated-orcid":false,"given":"Uro\u0161","family":"Bumba\u0161irevi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, dr Suboti\u0107a 8, 11000 Belgrade, Serbia"},{"name":"Clinic of Urology, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8935-7629","authenticated-orcid":false,"given":"Darko","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Urology, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-8041","authenticated-orcid":false,"given":"Darko","family":"Laketi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, dr Suboti\u0107a 8, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5162-3123","authenticated-orcid":false,"given":"\u017divoslav","family":"Te\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Belgrade, Studentski trg 12\u201316, 11158 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1403-4688","authenticated-orcid":false,"given":"Tomislav","family":"Tosti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Belgrade\u2014Institute of Chemistry, Technology and Metallurgy, Njego\u0161eva 12, 11158 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","first-page":"2533","article-title":"Development, Molecular Biology, and Physiology of the 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