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| Item Type: | Article |
|---|---|
| Title: | Serotonin regulates prostate growth through androgen receptor modulation |
| Creators Name: | Carvalho-Dias, E., Miranda, A., Martinho, O., Mota, P., Costa, A., Nogueira-Silva, C., Moura, R.S., Alenina, N., Bader, M., Autorino, R., 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 |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Volume: | 7 |
| Number: | 1 |
| 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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