Serotonin regulates prostate growth through androgen receptor modulation
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/49011 |
Resumo: | Serotonin regulates prostate growth through androgen receptor modulation |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Serotonin regulates prostate growth through androgen receptor modulationCiências Médicas::Medicina BásicaScience & TechnologySerotonin regulates prostate growth through androgen receptor modulationAging 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.Projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) and Bolsa de Investigação GSK Inovação em Urologia 2012info:eu-repo/semantics/publishedVersionNature Publishing GroupUniversidade do MinhoDias, Emanuel CarvalhoMiranda, AliceMartinho, OlgaMota, PauloCosta, Ângela Margarida AmorimNogueira-Silva, CristinaMoura, Rute S.Alenina, NataliaBader, MichaelAutorino, RiccardoLima, Estêvão Augusto Rodrigues deCorreia-Pinto, Jorge2017-11-032017-11-03T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/49011engCarvalho-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), 154282045-232210.1038/s41598-017-15832-529133842https://www.nature.com/articles/s41598-017-15832-5info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:32:07Zoai:repositorium.sdum.uminho.pt:1822/49011Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:27:28.454019Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Serotonin regulates prostate growth through androgen receptor modulation |
title |
Serotonin regulates prostate growth through androgen receptor modulation |
spellingShingle |
Serotonin regulates prostate growth through androgen receptor modulation Dias, Emanuel Carvalho Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Serotonin regulates prostate growth through androgen receptor modulation |
title_full |
Serotonin regulates prostate growth through androgen receptor modulation |
title_fullStr |
Serotonin regulates prostate growth through androgen receptor modulation |
title_full_unstemmed |
Serotonin regulates prostate growth through androgen receptor modulation |
title_sort |
Serotonin regulates prostate growth through androgen receptor modulation |
author |
Dias, Emanuel Carvalho |
author_facet |
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 |
author_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
Ciências Médicas::Medicina Básica Science & Technology |
topic |
Ciências Médicas::Medicina Básica Science & Technology |
description |
Serotonin regulates prostate growth through androgen receptor modulation |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-11-03 2017-11-03T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/49011 |
url |
http://hdl.handle.net/1822/49011 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
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 2045-2322 10.1038/s41598-017-15832-5 29133842 https://www.nature.com/articles/s41598-017-15832-5 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132765965254656 |