{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T17:30:37Z","timestamp":1768411837603,"version":"3.49.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T00:00:00Z","timestamp":1510531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T00:00:00Z","timestamp":1510531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aging and testosterone almost inexorably cause benign prostatic hyperplasia (BPH) in Human males. However, etiology of BPH is largely unknown. Serotonin (5-HT) is produced by neuroendocrine prostatic cells and presents in high concentration in normal prostatic transition zone, but its function in prostate physiology is unknown. Previous evidence demonstrated that neuroendocrine cells and 5-HT are decreased in BPH compared to normal prostate. Here, we show that 5-HT is a strong negative regulator of prostate growth. <jats:italic>In vitro<\/jats:italic>, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). This 5-HT\u2019s inhibitory mechanism is also present in human cells of normal prostate and BPH, namely in cell lines expressing AR when treated with testosterone. In both models, 5-HT\u2019s inhibitory mechanism was replicated by specific agonists of <jats:italic>5-Htr1a<\/jats:italic> and <jats:italic>5-Htr1b<\/jats:italic>. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1(Tph1), we showed that <jats:italic>Tph1<\/jats:italic> knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type, whereas 5-HT treatment restored the prostate weight and AR levels. As 5-HT is decreased in BPH, we present here evidence that links 5-HT depletion to BPH etiology through modulation of AR. Serotoninergic prostate pathway should be explored as a new therapeutic target for BPH.<\/jats:p>","DOI":"10.1038\/s41598-017-15832-5","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T12:12:16Z","timestamp":1510056736000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Serotonin regulates prostate growth through androgen receptor modulation"],"prefix":"10.1038","volume":"7","author":[{"given":"Emanuel","family":"Carvalho-Dias","sequence":"first","affiliation":[]},{"given":"Alice","family":"Miranda","sequence":"additional","affiliation":[]},{"given":"Olga","family":"Martinho","sequence":"additional","affiliation":[]},{"given":"Paulo","family":"Mota","sequence":"additional","affiliation":[]},{"given":"\u00c2ngela","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Nogueira-Silva","sequence":"additional","affiliation":[]},{"given":"Rute S.","family":"Moura","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-5433","authenticated-orcid":false,"given":"Natalia","family":"Alenina","sequence":"additional","affiliation":[]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7045-7725","authenticated-orcid":false,"given":"Riccardo","family":"Autorino","sequence":"additional","affiliation":[]},{"given":"Est\u00eav\u00e3o","family":"Lima","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Correia-Pinto","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2017,11,13]]},"reference":[{"key":"15832_CR1","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ucl.2016.04.001","volume":"43","author":"KB Egan","year":"2016","unstructured":"Egan, K. 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