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https://hdl.handle.net/1822/49011
Título: | Serotonin regulates prostate growth through androgen receptor modulation |
Autor(es): | 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 |
Data: | 3-Nov-2017 |
Editora: | Nature Publishing Group |
Revista: | Scientific Reports |
Citação: | Carvalho-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 |
Resumo(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. |
Tipo: | Artigo |
Descrição: | Serotonin regulates prostate growth through androgen receptor modulation |
URI: | https://hdl.handle.net/1822/49011 |
DOI: | 10.1038/s41598-017-15832-5 |
ISSN: | 2045-2322 |
Versão da editora: | https://www.nature.com/articles/s41598-017-15832-5 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |