{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:19:43Z","timestamp":1791397183019,"version":"4.3.3"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>\n                    Estrogen receptor \u03b2 (ER\u03b2) plays an important role in both the mouse and human prostate. The endogenous ligand for ER\u03b2 is the dihydrotestosterone metabolite, 5\u03b2-androstane-3\u03b2, 17\u03b2-diol (3\u03b2-Adiol). Thus, treatment with 5-\u03b1 reductase inhibitor (5-ARI) should produce a phenotype similar to that seen in ER\u03b2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. By comparing RNA-Seq of the ventral prostates (VP) of ER\u03b2 knockout mice (ER\u03b2\n                    <jats:sup>crispr\u2212\/\u2212<\/jats:sup>\n                    ) and wild-type (WT) mice, we confirmed that ER\u03b2 modulates androgen receptor (AR) signaling indirectly by suppressing AR coactivators. Compared to WT mice, basal cell genes from ER\u03b2\n                    <jats:sup>crispr\u2212\/\u2212<\/jats:sup>\n                    mouse VP were significantly upregulated. A population of abnormal basal cells coexpressing P63 and AR was identified in the ER\u03b2\n                    <jats:sup>crispr\u2212\/\u2212<\/jats:sup>\n                    mouse VP by immunohistochemistry. In men treated with 5-ARI for treatment of benign prostatic hyperplasia (BPH), there was induction of a P63-positive intermediate cell population characterized by down regulation of Krt14 without significant change in the expression of Krt15, upregulation of AR and NKX3.1, and increased proliferation. In both VP of aging ER\u03b2\n                    <jats:sup>crispr\u2212\/\u2212<\/jats:sup>\n                    mice and in human prostates after 5-ARI treatment, there was substantial immune infiltration. Testosterone treatment inhibited immune infiltration in the VP of ER\u03b2\n                    <jats:sup>crispr\u2212\/\u2212<\/jats:sup>\n                    mice. We conclude that ER\u03b2 is a gene critical in maintaining normal basal cells and modulating immune environment in the prostate. Its loss leads to histological changes suggesting prostatitis and increases the number of intermediate cells, which are considered to be the cells of origin of prostate cancers. We suggest that an ER\u03b2 agonist could protect against 5-ARI-induced inflammatory cell infiltration and defects in the basal cell layer in BPH.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2505797122","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T15:00:38Z","timestamp":1750690838000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["The role of estrogen receptor \u03b2 in maintaining basal cells and modulating the immune environment in the prostate"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2231-9528","authenticated-orcid":false,"given":"Wan-fu","family":"Wu","sequence":"first","affiliation":[{"name":"Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-977X","authenticated-orcid":false,"given":"Xiao-yu","family":"Song","sequence":"additional","affiliation":[{"name":"Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Warner","sequence":"additional","affiliation":[{"name":"Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otabeck","family":"Imamov","sequence":"additional","affiliation":[{"name":"Tiohundra AB Norrt\u00e4lje Regional Hospital, Department of Surgery and Urology","place":["Norrt\u00e4lje, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Antonson","sequence":"additional","affiliation":[{"name":"Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institutet, Novum","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1472-1373","authenticated-orcid":false,"given":"Jan-Ake","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston","place":["Houston"]},{"name":"Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institutet, Novum","place":["Stockholm, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajur.2017.06.003"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/iju.15446"},{"key":"e_1_3_4_3_2","first-page":"30","article-title":"The etiology and pathophysiology genesis of benign prostatic hyperplasia and prostate cancer: A new perspective","volume":"8","author":"Phua T. 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Horvath , Frequent loss of estrogen receptor-beta expression in prostate cancer. Cancer Res. 61, 5331\u20135335 (2001).","journal-title":"Cancer Res."},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117772108"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0226057"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","unstructured":"J. S. 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Wu ERbeta KO mouse prostate RNA-Seq.xlsx. Figshare. https:\/\/figshare.com\/s\/6bf0542fe3ec23e12963. Deposited 20 May 2025."},{"key":"e_1_3_4_47_2","unstructured":"W. Wan-fu A. Antoson Data from \u201cThe RNA-Seq data for 12-mo-old ER\u03b2crispr-\/- (an ER\u03b2 knockout mouse by using CRISPR\/Cas9 technology) and wild type (WT) mouse ventral prostates.\u201d Figshare. https:\/\/doi.org\/10.6084\/m9.figshare.29109992.v1. 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