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Serotonin regulates prostate growth through androgen receptor modulation

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Item Type:Article
Title:Serotonin regulates prostate growth through androgen receptor modulation
Creators Name:Carvalho-Dias, E. and Miranda, A. and Martinho, O. and Mota, P. and Costa, A. and Nogueira-Silva, C. and Moura, R.S. and Alenina, N. and Bader, M. and Autorino, R. and Lima, E. and Correia-Pinto, J.
Abstract: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.
Keywords:5-HT1 Serotonin Receptors, Androgen Receptors, Animal Disease Models, Cell Line, Down-Regulation, Knockout Mice, Neuroendocrine Cells, Newborn Animals, Organ Culture Techniques, Organ Size, Prostate, Prostatic Hyperplasia, Serotonin, Serotonin 5-HT1 Receptor Agonists, Testosterone, Tryptophan Hydroxylase, Up-Regulation, Animals, Mice, Rats
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:15428
Date:13 November 2017
Official Publication:https://doi.org/10.1038/s41598-017-15832-5
PubMed:View item in PubMed

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