Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement

Haghsheno, Mohammad-Ali; Mellström, Dan; Peeker, Ralph; Hammarsten, Jan; Lorentzon, Mattias; Sundh, Valter; Karlsson, Magnus K.; Ohlsson, Claes; Damber, Jan‐Erik

doi:10.3109/21681805.2014.936495

Cited by 12 publications

(11 citation statements)

References 29 publications

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“…Overall, it may suggest that pharmacological modulation of peripheral 5-HT can be used to efficiently increase prostatic 5-HT and, in this way, inhibit prostatic growth. These findings are also consistent with a preceding study in a large cohort of human males, that established that LUTS were associated with benign prostate increase and plasmatic 5-HT decrease 10 . Furthermore, Sayed et al showed that dapoxetine, a selective serotonin reuptake inhibitor, may inhibit prostatic growth significantly 23 .…”

Section: Discussionsupporting

confidence: 93%

“…Importantly, in the prostate, 5-HT is one of the most abundant neuroendocrine factors present in neuroendocrine cells (NEC) 9 . It has been reported, in a large humans study, that LUTS were associated with BPH and, at the same time, with a decrease in plasmatic 5-HT concentration 10 . Several reports have also demonstrated that NEC and 5-HT are significantly decreased in BPH when compared to normal prostate 11 – 13 .…”

Section: Introductionmentioning

confidence: 84%

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Effects of testosterone replacement on serotonin levels in the prostate and plasma in a murine model of hypogonadism

Mota

Barbosa-Martins

Moura

et al. 2020

Sci Rep

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Benign prostate hyperplasia is a dysfunctional disease with an elevated prevalence. Despite the accepted impact of aging and testosterone (TES) in its pathophysiology, its aetiology remains unknown. Recent studies described that serotonin (5-HT) inhibits benign prostate growth through the modulation of the androgen receptor, in the presence of TES. Accordingly, this work aimed to determine the impact of castration and TES replacement in plasmatic and prostatic 5-HT regulation. C57BL/6 mice were submitted to surgical castration and divided into three groups, continually exposed to either vehicle or different TES doses for 14 days. Plasmatic 5-HT concentration was measured before and after castration, and after TES reintroduction. Finally, total prostatic weight and intra-prostatic 5-HT were determined in the different groups. Our results demonstrate that mice prostate exhibits high 5-HT tissue levels and that intra-prostatic total 5-HT was independent of castration or TES reintroduction, in all studied groups. Also, 5-HT plasmatic concentration significantly increased after castration and then normalized after TES administration. Our findings revealed that mice prostate has a high 5-HT content and that total prostatic 5-HT levels do not depend on androgens’ action. On the other hand, castration induced a significant increase in plasmatic 5-HT concentration, raising the hypothesis that androgens might be regulating the production of extra-prostatic 5-HT.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 84%

Effects of testosterone replacement on serotonin levels in the prostate and plasma in a murine model of hypogonadism

Mota

Barbosa-Martins

Moura

et al. 2020

Sci Rep

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“…Also 5-HT was shown to be significantly depleted in BPH tissue 19 . Furthermore, a recent study in a large cohort of Scandinavian men revealed that LUTS are associated with benign prostate enlargement and to decreased plasmatic 5-HT concentration 21 . These findings suggest a potential link between prostatic 5-HT depletion and BPH etiology; however, the function of 5-HT in regulation of benign prostate growth has never been studied.…”

Section: Introductionmentioning

confidence: 99%

Serotonin regulates prostate growth through androgen receptor modulation

Carvalho-Dias

Miranda

Martinho

et al. 2017

Sci Rep

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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.Benign prostatic hyperplasia (BPH) is one of the main causes of non-neurogenic lower urinary tract symptoms (LUTS) in the aging male 1,2 . The underlying mechanism responsible for BPH is not understood, and only elucidating the etiology of BPH will increase our ability to treat or even prevent its development.Currently the most accepted hypothesis for the etiology of BPH is, that proposed by McNeal, in which BPH results from the reawakening of inductive potential in adult prostatic stroma in a specific prostatic region defined as transition zone [3][4][5] . This hypothesis claimed that the adult prostatic epithelium retains the ability to respond to inductive stromal signaling with new ductal branching morphogenesis 6,7 . However this hypothesis does not respond to the critical question of why this reawakening of human adult prostatic stroma occurs.While there is no BPH without testosterone 8 , testosterone levels decrease with age 9,10 and no direct correlation between testosterone concentration and prostate volume has been established yet 11 . Moreover, it is widely accepted that physiologic concentrations of testosterone provide an excess of testosterone for optimal prostatic growth suggesting that testosterone is not the etiologic factor responsible for BPH 12 . On the other hand, several reports have documented an up-regulation of the androgen receptor (AR) in BPH tissue, unveiling a potential role for AR in BPH etiopathogenesis [13][14][15] . The neuroendocrine prostatic cells secrete various neuroendocrine factors with 5-HT being one of the most abundant. The peculiar morphology of some neuroendocrine cells with dendritic processes extending to lumen and projection...

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“…In RCTs, the effect of MetS components on LUTS is unclear because taking a random sample of men and women in the community does mean disorders of the uropoietic system will be present in the sample. 13,42,46 Furthermore, all RCTs are hypothetically designed for sample following a power calculation with 95% CI ( p = 0.05). Even if results are significant, there is a 5% chance they are due to chance.…”

Section: Discussionmentioning

confidence: 99%

Metabolic syndrome is associated with prostate enlargement: a systematic review, meta-analysis, and meta-regression on patients with lower urinary tract symptom factors

Omran

Leca

Oštarijaš

et al. 2021

Therapeutic Advances in Endocrinology

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Background: Metabolic syndrome (MetS) is defined by at least three of the following five criteria: blood pressure ⩾130/85 mmHg, fasting blood glucose ⩾5.6 mmol/l, triglycerides concentration ⩾1.7 mmol/l, waist circumference ⩾102 cm (for men), and high-density lipoprotein cholesterol concentration <1.03 mmol/l (for men). MetS has been associated with worse lower urinary tract symptoms (LUTS) and higher International Prostate Symptom questionnaire scores. Materials and Methods: MEDLINE, Cochrane, ClinicalTrials.gov, and SCOPUS were critically appraised for all peer-reviewed manuscripts that suitably fulfilled our protocol’s inclusion criteria established a priori. Meta-analytical and meta-regression calculations were performed in R using the Sidik–Jonkman and Hartung–Knapp random effects model and predefined covariates. Results: A total of 70 studies ( n = 90,206) were included in qualitative synthesis. From these, 60 studies focused on MetS and LUTS: 44 reported positive correlations, 5 reported negative correlations, 11 reported no association, and 10 studies focused on MetS and total prostate volume (TPV). MetS positively correlated with moderate LUTS [odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.35–1.80], severe LUTS (OR = 2.35, 95% CI = 1.82–3.03), overactive bladder (OAB; OR = 3.2, 95% CI = 1.6–5.8), and nocturia severity (OR = 2.509, 95% CI = 1.571–4.007) at multivariate analysis. A total of 30 studies ( n = 22,206) were included in meta-analysis; MetS was significantly associated with higher TPV (mean differences = 4.4450 ml, 95% CI = 2.0177–6.8723), but no significant predictive factors for effect sizes were discovered. Conclusion: Our meta-analysis demonstrates a significant association between the aggravating effects of MetS, which commonly coexists with obesity and benign prostate enlargement.

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Lower urinary tract symptoms are associated with low levels of serum serotonin, high levels of adiponectin and fasting glucose, and benign prostatic enlargement

Cited by 12 publications

References 29 publications

Effects of testosterone replacement on serotonin levels in the prostate and plasma in a murine model of hypogonadism

Effects of testosterone replacement on serotonin levels in the prostate and plasma in a murine model of hypogonadism

Serotonin regulates prostate growth through androgen receptor modulation

Metabolic syndrome is associated with prostate enlargement: a systematic review, meta-analysis, and meta-regression on patients with lower urinary tract symptom factors

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