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TitleSerotonin regulates prostate growth through androgen receptor modulation
Author(s)Dias, Emanuel Carvalho
Miranda, Alice
Martinho, Olga
Mota, Paulo
Costa, Ângela Margarida Amorim
Nogueira-Silva, Cristina
Moura, Rute S.
Alenina, Natalia
Bader, Michael
Autorino, Riccardo
Lima, Estêvão Augusto Rodrigues de
Correia-Pinto, Jorge
Issue date3-Nov-2017
PublisherNature Publishing Group
JournalScientific Reports
CitationCarvalho-Dias, E., Miranda, A., Martinho, O., Mota, P., Costa, Â., Nogueira-Silva, C., ... & Lima, E. (2017). Serotonin regulates prostate growth through androgen receptor modulation. Scientific reports, 7(1), 15428
Abstract(s)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. In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). This 5-HT's 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's inhibitory mechanism was replicated by specific agonists of 5-Htr1a and 5-Htr1b. Since peripheral 5-HT production is specifically regulated by tryptophan hydroxylase 1(Tph1), we showed that Tph1 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.
DescriptionSerotonin regulates prostate growth through androgen receptor modulation
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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