5-alpha reductase

5 - α 还原酶
  • 文章类型: Journal Article
    In addition to dermatological complications, acne can affect the quality of life of individuals in numerous ways, such as employment, social habits and body dissatisfaction. According to our expertise, caprylic acid and propanediol would not have a direct action on Cutibacterium acnes. Despite this, we investigated the existence of a synergistic effect among xylitol, caprylic acid and propanediol as a mixture of compounds representing a single topical active ingredient that could benefit the treatment against acne. In vitro and in vivo assays were performed to challenge and to prove the efficacy of propanediol, xylitol and caprylic acid (PXCA) against acne. PXCA had its MIC challenged against C. acnes (formerly Propionibacterium acnes) and Staphylococcus aureus, resulting in concentrations of 0.125% and 0.25%, respectively, and it also developed antimicrobial activity against C. acnes (time-kill test). PXCA was able to reduce the 5-alpha reductase expression in 24% (p < 0.01) in comparison with the testosterone group. By the end of 28 days of treatment, the compound reduced the skin oiliness, porphyrin amount and the quantity of inflammatory lesions in participants. According to the dermatologist evaluation, PXCA improved the skin\'s general appearance, acne presence and size.
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  • 文章类型: Journal Article
    据报道,蔓越莓粉(CR)可有效对抗下尿路症状(LUTS)和复发性尿路感染。50岁以上男性的良性前列腺增生(BPH)是LUTS的常见原因。这里,我们尝试使用BPH诱导的大鼠模型评估CR是否也对治疗BPH有效,口服CR。体重200-250g的雄性Sprague-Dawley大鼠随机分为以下6组(n=9):非去势组;去势组;BPH和蔓越莓8周(CR8W)组;BPH和蔓越莓4周(CR4W)组;BPH和锯棕榈组(锯棕榈)。与BPH组相比,CR8W组显示前列腺重量显著下降(33%),双氢睾酮(DHT)水平(血清中18%,前列腺中28%),5-α还原酶水平(1型减少18%,2型减少35%),和组织学变化。这些结果表明CR可以通过抑制5-α还原酶和通过降低其他生物标志物如前列腺重量和DHT水平来减弱BPH。因此,CR可能是开发用于BPH治疗的功能性食品的有效候选物。IACUC(USW-IACUC-R-2015-004)。
    Cranberry powder (CR) is reported to be effective against lower urinary tract symptoms (LUTS) and recurrent urinary tract infections. Benign prostatic hyperplasia (BPH) in men older than 50 years is a common cause of LUTS. Here, we attempted to evaluate if CR is also effective for treating BPH using a BPH-induced rat model, which was orally administered CR. Male Sprague-Dawley rats weighing 200-250 g were randomly divided into the following six groups (n = 9): noncastration group; castration group; BPH group; BPH and cranberry for 8-week (CR8W) group; BPH and cranberry for 4-week (CR4W) group; and BPH and saw palmetto group (saw palmetto). Compared with the BPH group, the CR8W group showed a significant decrease in prostate weight (by 33%), dihydrotestosterone (DHT) levels (by 18% in serum and 28% in prostate), 5-alpha reductase levels (18% reduction of type 1 and 35% of type 2), and histological changes. These results indicate that CR could attenuate BPH by inhibiting 5-alpha reductase and by reducing other biomarkers such as prostate weight and DHT levels. Thus, CR may be an effective candidate for the development of a functional food for BPH treatment. IACUC (USW-IACUC-R-2015-004).
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  • 文章类型: Journal Article
    人们普遍认为性类固醇,即睾丸激素和性腺来源的17β-雌二醇(E2),控制海马的突触可塑性。当发现这些性类固醇是在海马体中合成的时,出现了一种新的范例。海马中性类固醇的抑制作用会损害大脑该区域的突触可塑性。在性腺切除的动物和海马培养物中,在雌性动物和雌性动物的培养物中抑制雌二醇的合成,在雄性动物和雄性动物的培养物中抑制二氢睾酮的合成,导致突触丢失并损害海马中的LTP,但反之亦然。由于海马培养物起源于围产期动物,由于体内和体外研究结果的相似性,在围产期发生性印记时,海马神经元似乎以性别特异性方式分化。
    It was a widely held belief that sex steroids, namely testosterone and 17β-estradiol (E2) of gonadal origin, control synaptic plasticity in the hippocampus. A new paradigm emerged when it was shown that these sex steroids are synthesized in the hippocampus. The inhibition of sex steroids in the hippocampus impairs synaptic plasticity sex-dependently in this region of the brain. In gonadectomized animals and in hippocampal cultures, inhibition of estradiol synthesis in female animals and in cultures from female animals, and inhibition of dihydrotestosterone synthesis in male animals and in cultures of male animals, cause synapse loss and impair LTP in the hippocampus, but not vice versa. Since the hippocampal cultures originated from perinatal animals, and due to the similarity of in vivo and in vitro findings, it appears that hippocampal neurons are differentiated in a sex-specific manner during the perinatal period when sexual imprinting takes place.
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  • 文章类型: Journal Article
    脱发(AGA)是最常见的毛发疾病,影响了大约50%的男性和女性。一种含有两种专利配方(Redensyl和SepicontrolA5)的外用乳液,已被引入作为AGA标准疗法的替代方法。44例AGA患者被随机分配使用活性洗剂或赋形剂,每天两次,共24周。在第0、12和24周通过临床检查对受试者进行评估,摄影文档,生活质量评估(DLQI),和毛色图(生长期与睡眠原之比)。41名患者,18男23女,完成研究。在接受积极治疗的患者中(n=26),7.7%有很大改善,73.1%有中度改善,19.2%保持稳定。中位自我评估得分从基线时的4分增加到24周时的6分(P<.001),而DLQI分别从4提高到3(P<.001)。在第0周、第12周和第24周,中位生长期与静止期比值分别从2.25增加到4.00,再增加到6.02。未报告显著不良事件。这种新的局部活性混合物是有效的治疗AGA,患者满意度高,提高生活质量,和出色的安全性。因此,它可能是AGA的一种有用的替代治疗方法。
    Αndrogenetic alopecia (AGA) is the most common hair disorder, affecting approximately 50% of men and women. A topical lotion that contains two patented formulas (Redensyl and Sepicontrol A5), has been introduced as an alternative approach to standard therapies for AGA. Forty-four patients with AGA were randomized either to apply the active lotion or the vehicle, twice daily for 24 weeks. Subjects were evaluated at 0, 12, and 24 weeks by clinical examination, photographic documentation, quality of life evaluation (DLQI), and trichogram (anagen-to-telogen ratio). Forty-one patients, 18 males and 23 females, completed the study. Among patients receiving active treatment (n = 26), 7.7% had great improvement, 73.1% had moderate improvement, and 19.2% remained stable. The median self-assessment score increased from 4 at baseline to 6 at 24 weeks (P < .001), while the DLQI improved from 4 to 3, respectively (P < .001). The median anagen-to-telogen ratio increased from 2.25 to 4.00 to 6.02 at weeks 0, 12, and 24, respectively. No significant adverse events were reported. This new topical active blend is effective in the treatment of AGA, with high degree of patients\' satisfaction, improvement of quality of life, and an excellent safety profile. Thus, it may represent a useful alternative therapeutic approach for AGA.
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  • 文章类型: Letter
    初步观察到入院的COVID-19患者中男性型脱发的频率很高,表明雄激素表达可能是COVID-19严重程度的线索。
    A preliminary observation of high frequency of male pattern hair loss among admitted COVID-19 patients and suggest that androgen expression might be a clue to COVID-19 severity.
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  • 文章类型: Journal Article
    研究了用50kGyγ射线(HKC)辐照的高山红景天提取物对良性前列腺增生(BPH)的影响。7周龄雄性SD大鼠皮下注射20mg/kg丙酸睾酮(TP)诱导BPH。然后,只有睾酮的组接受了睾酮,睾酮+非那雄胺组接受睾酮和非那雄胺(5mg/kg),睾酮+HKC组接受睾酮和HKC提取物(500mg/kg).测定血清或前列腺组织中的前列腺重量和二氢睾酮(DHT)水平。还测量了前列腺组织中5-α还原酶(AR)的mRNA表达。与对照组相比,TP组的前列腺重量显著改善,HKC和非那雄胺治疗组的前列腺重量降低.此外,在HKC和非那雄胺治疗组中,前列腺中5-AR的mRNA表达显著降低.同样,α-平滑肌肌动蛋白(α-SMA)和细胞角蛋白的表达水平,在HKC和非那雄胺组中与前列腺增大有关,远低于TP组。HKC治疗对睾酮诱导的BPH大鼠的疗效与非那雄胺治疗相似。HKC可能被开发为BPH治疗的潜在新药。
    The effect of Rhodiola sachalinensis Boriss extract irradiated with 50 kGy gamma rays (HKC) on benign prostatic hyperplasia (BPH) was investigated. Seven-week-old male SD rats received a subcutaneous injection of 20 mg/kg of testosterone propionate (TP) to induce BPH. Then, the testosterone only group received testosterone, the testosterone + finasteride group received testosterone and finasteride (5 mg/kg), the testosterone + HKC group received testosterone and HKC extract (500 mg/kg). Prostate weight and the dihydrotestosterone (DHT) levels in serum or prostate tissue were determined. The mRNA expressions of 5-alpha reductase (AR) in prostate tissue were also measured. Compared to the control group, prostate weight was significantly improved in the TP group and decreased in the HKC and finasteride-treated groups. Furthermore, the mRNA expression of 5-AR in the prostate was significantly reduced in the HKC and finasteride-treated groups. Similarly, the expression levels of α-smooth muscle actin (α-SMA) and cytokeratin, which are associated with prostatic enlargement in the HKC and finasteride groups, were much lower than in the TP group. HKC treatment showed similar efficacy to finasteride treatment on rats with testosterone-induced BPH. HKC may be explored as a potential new drug for BPH treatment.
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  • 文章类型: Journal Article
    背景:性类固醇在前列腺组织生长中的具体参与尚不清楚。血浆和良性中央前列腺新鲜手术样品中的性类固醇浓度与前列腺体积相关。
    方法:2014年9月至2017年1月进行单中心前瞻性研究。年龄,肥胖参数,收集血清和前列腺内的性类固醇浓度,符合最新的内分泌学会指南和GC/MS评估的类固醇。根据年龄和体重指数(BMI)调整统计计算。
    结果:32名患者,正常和高容量前列腺组平分,包括在分析中。高容量前列腺患者年龄较大,体重较重,BMI较高。经年龄和BMI调整后的比较显示,高容量前列腺中DHT浓度较高。正常和高容量前列腺组织都以类似的方式浓缩性类固醇。组织内酶活性替代标记物比率的比较突出了相似的TT/E1和TT/E2比率,在高容量前列腺中,较高的DHT/E1比率和较低的DHT/PSA比率。
    结论:STERPROSER试验提供了大量前列腺中DHT浓度较高的证据,这可能反映了较高的5-α还原酶表达或较低的下游代谢酶的表达,例如3a-氢化类固醇脱氢酶。
    BACKGROUND: The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume.
    METHODS: Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI).
    RESULTS: Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates.
    CONCLUSIONS: STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase.
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  • 文章类型: Journal Article
    Androgenetic alopecia (AGA) affects approximately 70% of men and 40% of women in an age-dependent manner and is partially mediated by androgen hormones. Benign prostatic hyperplasia (BPH) similarly affects 50% of the male population, rising by 10% each decade. Finasteride inhibits 5-alpha reductase (5AR) and is used to treat both disorders, despite offering limited clinical benefits accompanied by significant adverse side effects. Building on our previous work demonstrating the efficacy of naturally derived 5AR inhibitors (such as stigmasterol and beta sitosterol), we hypothesize that targeting 5AR as well as inflammatory pathways may yield improved efficacy in AGA and BPH. Here we address these dual pathomechanisms by examining the potency of a novel composition using in vitro assays of representative cell lines for AGA (hair follicle dermal papilla cells) and BPH (LNCaP prostate cells), respectively. Exposure of cells to the novel test composition down-regulated mRNA expression profiles characteristic of both disease processes, which outperformed finasteride. Changes in mRNA expression were corroborated at the protein level as assessed by western blotting. These studies provide proof of concept that novel, naturally derived compositions simultaneously targeting 5AR and inflammatory mediators may represent a rational approach to treating AGA and BPH. Copyright © 2016 John Wiley & Sons, Ltd.
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  • 文章类型: Comparative Study
    OBJECTIVE: Male androgenetic alopecia (AGA) is a common hair problem. Serenoa repens extract has been shown to inhibit both types of 5-α reductase and, when taken orally, has been shown to increase hair growth in AGA patients. The aim of this study was to assess the efficacy of topical products containing S. repens extract for the treatment of male AGA.
    METHODS: This was a pilot, prospective, open, within-subject comparison limited to 24 weeks using no placebo controls. In all, 50 male volunteers aged between 20 and 50 years received topical S. repens products for 24 weeks. The primary end-point was a hair count in an area of 2.54 cm(2) at week 24. Secondary end-points included hair restoration, investigators\' photographic assessment, patients\' evaluation and discovering adverse events.
    RESULTS: The average hair count and terminal hair count increased at weeks 12 and 24 compared to baseline. Some of these positive results levelled off at week 24, presumably because the concentrated topical product containing S. repens extract was stopped after 4 weeks. The patients were satisfied with the products and the side-effects were limited.
    CONCLUSIONS: The topical application of S. repens extract could be an alternative treatment in male pattern baldness in male patients who do not want or cannot tolerate the side-effects of standard medications, but the use of a concentrated S. repens product beyond 4 weeks may be necessary for sustained efficacy.
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  • 文章类型: Journal Article
    We investigate the impact of dutasteride on prostate specific antigen (PSA) and prostate volume in men receiving testosterone (T) therapy. Twenty-three men on stable dose T therapy were randomised to receive either dutasteride or placebo for 12 months. Serum levels of PSA, T and dihydrotestosterone (DHT) and responses to the International Index of Erectile Function (IIEF) and Male Sexual Health Questionnaire (MSHQ) questionnaires were determined at baseline and at 3, 6, 9 and 12 months. Prostate volume (PV) was measured using transrectal ultrasound (TRUS) at baseline and again after 12 months. A total of 22 men (mean age 57.3) completed the study, with 11 men receiving placebo and 11 receiving dutasteride. Men receiving dutasteride had a significant decrease in PSA (-0.46 ± 0.81 ng ml(-1) ; P = 0.04) and in PV (-6.65 ± 11.0%; P = 0.03) from baseline over 12 months. DHT decreased significantly for men on dutasteride compared with men receiving placebo (P = 0.02). When compared with men who received placebo, men who received dutasteride demonstrated nonsignificant trends towards decreased PSA (-0.46 versus 0.21 ng ml(-1) ; P = 0.11), PV (-6.65% versus 3.4%; P = 0.08) and MSHQ scores (-10.2 versus 5.6; P = 0.06). Dutasteride reduces PSA and PV for men on T therapy, but perhaps less so than in men without T therapy.
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