Relationship of neuroendocrine cells of prostate and serotonin to benign prostatic hyperplasia

Cockett, Abraham T.K.; Sant'Agnese, Paul A. di; Gopinath, Prabhu; Schoen, Susan R.; Abrahamsson, Per‐Anders

doi:10.1016/0090-4295(93)90260-h

Cited by 66 publications

(42 citation statements)

References 23 publications

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“…One of the important facts in this area is that the number of NE cells increases in prostatic tissue with age [14]. Another fact is that a larger number of NE cells are found in smaller nodules of BPH tissue than in adjacent, normal prostatic tissue [7]. For both these reasons, we investigated the possibility that serotonin may be a cause of LUTS in BPH patients.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, part of the peripheral nervous system within the prostate seems to be responsible for some of the irritative symptoms. Also, Cockett et al [7] and Abrahamsson et al [8] demonstrated that when smaller nodules of BPH were studied, the neuroendocrine (NE) cells were equal to or increased in number compared with those in adjacent normal prostatic tissue.…”

Section: Introductionmentioning

confidence: 99%

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Acute Effects of Serotonin on Rat Bladder Contractility

Kim

Lee²,

Kim³

et al. 2002

Urol Int

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Introduction: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, it examines which drugs inhibit the serotonin-induced detrusor contractions. Materials and Methods: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001–0.01 mM) on resting tension were assessed. Electrical field stimulation (EFS); bethanechol (0.0001–0.01 mM); ATP (1–3 mM)- or KCl (63.5–254 mM)-induced contractions using an application in an organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS-, bethanechol-, ATP- or KCl-induced contraction on serotonin treatment (0.001 mM) was assessed and serotonin (0.001–0.1 mM) was cumulatively added to the organ bath following preincubation with propranolol, ketanserin, tropisetron, propiverine, sodium nitroprusside or doxazosin. Results: The serotonin-induced response has two phases: an initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001 mM serotonin (p < 0.05). There was no effect on the responses to ATP, KCl, or EFS on 0.001 mM serotonin. The 5-HT₂ receptor is mainly responsible for serotonin-induced contractions of the detrusor (p < 0.05), while the 5-HT₁ receptor is partially responsible. Doxazosin and propiverine each significantly suppressed the response to serotonin, while sodium nitroprusside and tropisetron each had no effect (p < 0.05). Conclusions: Because the 5-HT₂ antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT₂ antagonist seems to improve lower urinary tract symptoms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Acute Effects of Serotonin on Rat Bladder Contractility

Kim

Lee²,

Kim³

et al. 2002

Urol Int

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“…7 This notion is supported by the observation that the proliferation index of cancer cells surrounding NE cells is higher than that of distal cancer cells. 30,31 Pathogenetic factors responsible for the development of the androgen-resistant phenotype are detectable in PC tissues long before the clinical onset of the disease 32 but usually escape clinical detection and attention. Some authors have found that the acquisition of NE characteristics is fully reversible, 20 thus early detection and prevention of castration resistant PC may provide a new strategy to improve survival of patients diagnosed with PC at risk to fail standard androgen deprivation therapy.…”

Section: Discussionmentioning

confidence: 99%

Regulation of neuroendocrine differentiation by AKT/hnRNPK/AR/β‐catenin signaling in prostate cancer cells

Ciarlo

Benelli

Barbieri

et al. 2011

Intl Journal of Cancer

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Current diagnostic tools cannot predict clinical failure and androgen-independent disease progression for patients with prostate cancer (PC). The survival signaling pathways of prostate cells play a central role in the progression of tumors to a neuroendocrine (NE) phenotype. NE cells demonstrate attributes that suggest that they are an integral part of the signaling cascade leading to castration-resistant PC. In this study, making use of in vitro neuroendocrine differentiation (NED) of human LNCaP and mouse TRAMP-C2 cells after androgen withdrawal, and of the transgenic adenocarcinoma of mouse prostate (TRAMP) model, we characterized a sequence of molecular events leading to NED and identified a number of markers that could be detectable by routine analyses not only in castration resistant PC but also in hormone naïve PC at the time of initial diagnosis. We found that NED associates with AKT activation that in turn regulates heterogeneous nuclear ribonucleoprotein K (hnRNP K), androgen receptor (AR) and b-catenin levels. Addition of molecules targeting membrane-bound receptors and protein kinases blocks NE differentiation in LNCaP and TRAMP-C2 cells. The extent of AKT phosphorylation and hnRNP K, AR and b-catenin levels may have a potential value as prognostic indicators discriminating between androgen-responsive and unresponsive cells and could be used as molecular targets to monitor the anti-tumor action of new therapeutic protocols based on antireceptor agents and/or neuroendocrine hormone antagonists.PC is one of the most common malignancies among males in the western world and a major health problem in many industrialized countries. PC develops and progresses under the influence of androgenic steroids. This influence is consistent with the use of androgen depletion therapies to treat patients with advanced disease.1 However, most patients finally relapse with hormone-refractory prostate cancer and available treatment options are only palliative. Therefore, an understanding of what drives progression to androgen independence is critical. The prostate is known to be dependent not only on androgens but also on growth factors and neuropeptides secreted by NE cells that maintain normal prostate function and play a role in the development of pathological conditions.2 Adult prostate gland possesses basal (proliferating) cells, secretory (luminal) cells and the less abundant (<0.1%) NE cells. Approximately 10% of prostatic carcinoma reveals extensive and multifocal NE features and the presence of NE markers is usually associated with poor prognosis. 3,4 Interestingly, along with the androgen-independent status, an increase in the number of NE cells has been reported in some studies and long-term androgen ablation therapy tends to select prostate tumor populations that are enriched in NE cells.5 These cells lack nuclear androgen receptor 6 ; thus they represent an androgen-insensitive cell phenotype in the prostate and it has been hypothesized that NE cells can lead to the development and growth of androgen-refract...

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“…6 However, the guinea-pig prostate serves as a model for research on neuroendocrine (NE) cells; 7 a population of epithelial cells that are thought to be involved in normal prostate growth, hyperplasia and cancer development. [8][9][10][11] The aim of this experimental study was first to establish a model for testosterone administration, and then to study the effects of long-term maximal testosterone stimulation on the guinea-pig prostate.…”

Section: Introductionmentioning

confidence: 99%

Long-term testosterone stimulation induces hyperplasia in the guinea-pig prostate

Acosta

Dizeyi

Feinstein

et al. 2004

Prostate Cancer Prostatic Dis

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The relation between supraphysiologic circulating testosterone levels and prostatic diseases is unclear and difficult to study in men. Animal models may be advantageous. Based on a pilot study, testosterone enantate 50 mg (n ¼ 12) or 25 mg (n ¼ 12) was administered to guinea-pigs intramuscularly every 3 weeks, for either 7 or 14 months. The histopathology of the prostate was described. Epithelial hyperplasia was found in 14/21 animals receiving testosterone and in 7/12 very old animals, but no such changes were found in the sham or castrated animals. Testosterone stimulation seems to induce epithelial hyperplasia, but not cancer, in the guinea-pig prostate.

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Relationship of neuroendocrine cells of prostate and serotonin to benign prostatic hyperplasia

Cited by 66 publications

References 23 publications

Acute Effects of Serotonin on Rat Bladder Contractility

Acute Effects of Serotonin on Rat Bladder Contractility

Regulation of neuroendocrine differentiation by AKT/hnRNPK/AR/β‐catenin signaling in prostate cancer cells

Long-term testosterone stimulation induces hyperplasia in the guinea-pig prostate

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