Anoctamin 1 (TMEM16A) is essential for testosterone-induced prostate hyperplasia.
Ontology highlight
ABSTRACT:
SUBMITTER: Cha JY
PROVIDER: S-EPMC4534281 | biostudies-other | 2015 Aug
REPOSITORIES: biostudies-other
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:BackgroundBenign prostatic hyperplasia (BPH) is a common urological disorder reported among ageing men.ObjectiveThe study assessed histoprotective effect of lime essential oil (LEO) in a rat model of testosterone-induced benign prostatic hyperplasia (BPH) and evaluated its ability to reverse testosterone-mediated changes in the testis, kidney, and liver.Materials and methodsAdult Sprague Dawley (aged 12 weeks, 240-390 g) male rats were intramuscularly injected with testosterone enanthate (TE) (10 mg/kg) reconstituted in olive oil for ten days to establish benign prostatic hyperplasia (serum PSA level ≥ 1.24 ng/ml) in. After confirmation of BPH (sustained serum PSA level ≥ 1.24 ng/ml), rats in all groups (LEO: 30, 100, and 300 mg/kg, po, n = 6; finasteride: 15 mg/kg, po, n = 6) except model (BPH without treatment) and sham (no BPH and no treatment) groups were treated for 21 days. At the end of treatment, rats were anesthetised and blood was collected via cardiac puncture to determine serum PSA and total antioxidant capacity (TAC) levels. The prostate gland, testis, kidney, and liver were harvested, weighed, histologically processed and stained with H&E.ResultsLEO- and finasteride-treated groups recorded lesser mean prostatic weights relative to their model group. Baseline mean serum PSA level of LEO- and finasteride-treated groups reduced significantly (p < 0.05) relative to model group. Serum TAC levels were also higher in LEO- and finasteride-treated groups relative to model group. LEO-treated groups had less thickened glandular epithelium, smaller acini, fewer prostatic secretions and more fibromuscular stroma relative to model group. LEO and finasteride treatment produced improved histomorphological characteristics of testis, kidney, and liver compared to model group.ConclusionBy the current results, Citrus aurantifolia LEO may possess active agents that can be explored for translational medicine against BPH.
| S-EPMC6778952 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is a common urological disorder of men, characterized by prostatic enlargement and urethral obstruction. In this study, BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for 3 weeks. Tetracarpidium conophorum was administered daily by oral gavage at a dose of 100, 200 and 400 mg/kg BW of extract for three weeks, along with the TP injections and 5 mg/kg of finasteride for comparison. On day 21, the animals were sacrificed after anesthesia. Prostate were excised, weighed and used to determine relative prostate weight. Quantitative and qualitative phytochemical screening was also done and it showed the presence of flavonoids (0.370 mg/ml), tannins (0.458 mg/ml), phenols (0.508 mg/ml) and steroids (0.257 mg/ml). The prostate specific antigen level was evaluated, the result showed the data for extract group 200 mg/kg, 400 mg/kg, finasteride control group and BPH control group to be 0.186 ± 0.0023 ng/ml, 0.153 ± 0.005 ng/ml, 0.119 ± 0.0125 ng/ml and 0.332 ± 0.004 ng/ml respectively.
| S-EPMC6127981 | biostudies-literature
Project description:Epidemiologic studies revealed a context between lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and metabolic syndrome. However, molecular mechanisms underlying this relationship are largely unknown. Prostate enlargement and increased prostate smooth muscle tone are important factors in the pathophysiology of LUTS suggestive of BPH. In the present study, we studied effects of the metabolic hormone ghrelin on prostate enlargement in rats with experimentally induced BPH, growth of cultured stromal cells from human prostate (WPMY-1), and smooth muscle contraction of human prostate tissues. Ghrelin (20 nmol/kg daily, p.o., 2 weeks) increased prostate size in rats with testosterone-induced BPH. Microarray identified 114 ghrelin-upregulated genes (2-fold or more) in these prostates, with possible roles in growth, smooth muscle contraction, or metabolism. 12 genes were selected for further analyses. In human prostate tissues, mRNA levels of 11 of them correlated positively with ghrelin receptor (GHSR) expression, but only two with the degree of BPH. Accordingly, no correlation was evident between GHSR expression level and BPH in human prostate tissues. In WPMY-1 cells, the GHRS agonist MK0677 upregulated 11 of the selected genes. MK0677 induced proliferation of WPMY-1 cells, shown by EdU assay, colony formation, proliferation markers, flow cytometry, and viability. In myographic measurements, GHSR agonists enhanced contractions of human prostate strips. Together, ghrelin may aggravate prostate enlargement, stromal cell growth, and prostate smooth muscle contraction in BPH. Ghrelin may deteriorate urethral obstruction independently from BPH, qualifying the ghrelin system as an attractive new target to be tested for LUTS treatment in BPH.
| S-EPMC6893282 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is a noncancerous urinary disorder that is common in older adult men; however, its underlying mechanisms remain unclear. Fenugreek has some biological effects, including hyperglycemia regulation, immune response modulation, and anti-cancer properties; In this study, we investigated the ameliorative effects of fenugreek seed extract (Forceterone® [FCT]) in a testosterone propionate (TP)-induced BPH animal model and its mechanisms in BPH-1 human prostate epithelial cells. Sprague Dawley (SD) rats were injected subcutaneously with TP (3 mg/kg) for 8 weeks to induce BPH while FCT was administered orally at 25, 50, and 100 mg/kg. In addition, BPH-1 cells were used to evaluate the inhibitory effects on cell proliferation and examine inflammatory cytokine expression. Treating rats with FCT decreased prostate weight, dihydrotestosterone (DHT) level, and proliferating cell nuclear antigen (PCNA) expression in the prostate. Furthermore, it decreased androgen receptor (AR), 5α-reductase 2, B-cell lymphoma 2 (Bcl-2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and NF-κB expression in vitro and in vivo and increased Bcl-2-associated X protein (Bax) expression. FCT also inhibited cell proliferation dose dependently in BPH-1 cells. These findings showed the potential use of FCT as an alternative treatment for BPH.
| S-EPMC11818512 | biostudies-literature
Project description:ContextLespedeza cuneata G. Don (Fabaceae), has been used as a traditional treatment of various diseases. There is a report L. cuneata effects on hormone replacement therapy for endocrine-related disease. However, studies related to benign prostatic hyperplasia (BPH) have not been investigated.ObjectiveThe effects of L. cuneata aqueous extract (LCW) on testosterone-induced prostatic hyperplasia (TPH) were examined.Materials and methodsMale Wistar rats (10 weeks, 330-350 g) were randomly divided to 6 groups (n = 6): Control group; TPH group (3 mg/kg, s.c, daily); TPH + LCW (25, 50, 100 mg/kg); TPH + Finasteride 10 mg/kg for 6 weeks. At the end of treatment, histological change of prostate, serum dihydrotestosterone (DHT) level, mRNA expression of 5α-reductase, inflammatory factors, proliferating cell nuclear antigen (PCNA) and fibroblast growth factor-2 (FGF-2) in prostate were examined. Then, LCW was treated with BPH-1, a human BPH cell line, at 25, 50, 100 μg/mL for 24 h and examine mRNA level of androgen receptor (AR) and prostate-specific antigen (PSA). In addition, the content of vicenin-2 was analyzed.ResultsLCW treatment of TPH inhibited serum DHT levels by 54.5, 51.2 and 54.1% and mRNA expression of 5α-reductase were inhibited 54.3, 61.3 and 73.6%, respectively. In addition, mRNA expression of inflammatory factors, PCNA and FGF-2 were decreased in the prostate of rats. Also, LCW attenuated mRNA level of AR and PSA in BPH-1 cell. The content of vicenin-2 in the LCW was analyzed to 0.89 mg/g.Discussion and conclusionsBased on the results, LCW is a potential pharmacological candidate for the treatment of prostatic hyperplasia.
| S-EPMC6366415 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight &prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone-induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.
| S-EPMC4616049 | biostudies-other
Project description:Cinnamomi cortex (dried bark of Cinnamomum verum) is an important drug in Traditional Korean Medicine used to improve blood circulation and Yang Qi. Benign prostatic hyperplasia (BPH) is a common chronic disease in aging men. This study was conducted to determine the effect of Cinnamomi cortex water extract (CC) on BPH. BPH was induced by a pre-4-week daily injection of testosterone propionate (TP). Six weeks of further injection with (a) vehicle, (b) TP, (c) TP + CC, (d) TP + finasteride (Fi) was carried on. As a result, the prostate weight and prostatic index of the CC treatment group were reduced. Histological changes including epithelial thickness and lumen area were recovered as normal by CC treatment. The protein expressions of prostate specific antigen, estrogen receptor α (ERα), androgen receptor (AR), 5α-reductase (5AR), and steroid receptor coactivator 1 were suppressed by treatment of CC. Immunohistochemical assays supported the western blot results, as the expressions of AR and ERα were down-regulated by CC treatment as well. Further in vitro experiments showed CC was able to inhibit proliferation of RWPE-1 cells by suppressing 5AR and AR. These results all together suggest CC as a potential treatment for BPH.
| S-EPMC4994048 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is common among elderly men, of which inflammation, oxidative stress, proliferative, and apoptotic changes play important roles. Xialiqi (XLQ) capsule, a traditional Chinese herbal formula, is used as a potential drug in treating BPH. This study aims to evaluate the therapeutic effect of XLQ capsule on testosterone propionate- (TP-) induced BPH in rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: sham control, BPH model, high and low dose of XLQ, and finasteride as a positive control group. All groups were treated with appropriate drugs/normal saline for 28 consecutive days. Prostate weights were recorded; histopathological changes and content of IL-8, TNF-α, DHT, SOD, MDA, caspase-3, and PCNA of the prostate were determined. Animals with BPH demonstrated significantly increased prostate weights and prostate index, higher levels of IL-8, TNF-α, DHT, MDA, and PCNA, but lower activity of SOD and reduced expression of caspase-3. After treatment with XLQ, significant reductions of prostate weights, prostate index, IL-8, TNF-α, DHT, MDA, and PCNA, increased activity of SOD, and higher level of caspase-3 were shown. The present study indicates that XLQ can effectively prevent the development of TP-induced BPH model through mechanisms of anti-inflammation, antioxidation, antiproliferation, and proapoptosis.
| S-EPMC6186362 | biostudies-literature
Project description:Benign prostatic hyperplasia (BPH) is one of the most common diseases in the urinary system of elderly men. Pao extract is an herbal preparation of the bark of the Amazon rainforest tree Pao Pereira (Geissospermum vellosii), which was reported to inhibit prostate cancer cell proliferation. Herein we investigated the therapeutic potential of Pao extract against BPH development in a testosterone-induced BPH rat model. The administration of testosterone induced the prostate enlargement, compared with the sham operated group with vehicle treatment. The BPH/Pao group showed reduced prostate weight comparable with BPH/finasteride group. Notably, Pao treatment did not significantly reduce body weights and sperm number of rats, compared with the control group. Furthermore, Pao extract treatment reduced the proliferative index in prostate glands and testosterone-induced expression levels of AR, as well as androgen-associated proteins such as SRD5A1 and PSA. Moreover, Pao extract and its active component, flavopereirine, induced cytotoxicity on human prostate epithelial RWPE-1 cells in a dose- and time- dependent manner with G2/M arrest. Consistently, Pao extract and flavopereirine suppressed the expression levels of SRD5A1, AR and PSA, respectively. Together, these data demonstrated that Pao extract suppresses testosterone-induced BPH development through inhibiting AR activity and expression, and suggested that Pao extract may be a promising and relative safe agent for BPH.
| S-EPMC6928012 | biostudies-literature
Project description:IntroductionBenign prostatic hyperplasia (BPH) is a common disease among elderly men. Its pharmacological treatment is still unsatisfactory. 6-Paradol (6-PD) is an active metabolite found in many members of the Zingiberaceae family. It was reported to possess anti-proliferative, antioxidant, and anti-inflammatory activities. The present study aimed at exploring the potential of 6-PD to inhibit testosterone-induced BPH in rats as well as the probable underlying mechanism.MethodsMale Wistar rats were divided into 6 groups and treated as follows: Group 1 (control group) received vehicles only, Group 2 testosterone only, Groups 3 and 4 received 6-PD (2.5 and 5.0 mg/kg; respectively) and testosterone, and Group 6 received finasteride and testosterone.ResultsDaily treatment of animals with 6-PD at the two dose levels of 2.5 and 5 mg/kg significantly ameliorated a testosterone-induced rise in prostate index and weight. This was confirmed by histological examinations of prostatic tissues that indicated a reduction in the pathological changes as well as inhibition of the rise in glandular epithelial height in 6-PD treated rats. Immunohistochemical investigations showed that 6-PD prevented the up-regulation of cyclin D1 induced by testosterone injections. Further, 6-PD significantly modulated mRNA expression of both Bcl2 and Bax in prostate tissues of testosterone-treated rats in favor of anti-proliferation. It also showed antioxidant activities as evidenced by inhibition of accumulation of malondialdehyde (MDA) and exhaustion of catalase (CAT) activity. In addition, 6-PD displayed significant anti-inflammatory activities as it prevented up-regulation of interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB). Immunoblotting analysis revealed that 6-PD significantly inhibited testosterone-induced activation of AKT and mTOR in prostate tissues.Conclusions6-PD protects against testosterone-induced BPH in rats. This can be attributed, at least partly, to its antiproliferative, antioxidant, and anti-inflammatory properties as well as its ability to inhibit activation of the AKT/mTOR axis.
| S-EPMC9571361 | biostudies-literature