5-alpha reductase

5 - α 还原酶
  • 文章类型: Journal Article
    我们的目的是确定各种可用的口服,topic,以及雄激素性脱发患者脱发的程序性治疗选择。使用系统审查和荟萃分析指南的首选报告项目,对国家医学图书馆进行了系统评价.总的来说,141项独特研究符合我们的纳入标准。我们证明了许多非处方药(例如局部米诺地尔,补充剂,低水平光处理),处方(例如口服米诺地尔,非那雄胺,dutasteride),和程序(例如富血小板血浆,分馏激光器,毛发移植)治疗成功促进毛发生长,强调多方面和个性化管理方法的优越性。
    We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.
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  • 文章类型: Journal Article
    目的:尽管广泛使用5-α还原酶抑制剂(5-ARIs)治疗良性前列腺增生(BPH),某些BPH患者对5-ARIs治疗无反应。本文对BPH患者5-ARIs耐药机制的当前观点进行了全面概述,并整合了潜在的生物标志物和5-ARIs耐药的潜在治疗选择。这些发现可能有助于开发新的或优化更有效的治疗方案,并促进BPH的个性化医疗。
    结果:某些BPH患者对5-ARIs耐药的途径包括表观遗传修饰,激素水平的变化,自噬过程,以及雄激素受体结构的变化,这些途径最终可能归因于炎症。有希望的,新型生物标志物,包括膀胱内前列腺突出,炎症因子,和单核苷酸多态性,可以提供对5-ARIs治疗反应性的预测性见解,授权医生微调治疗策略。此外,在地平线上,GV1001和mTOR抑制剂已成为未来解决BPH的潜在替代治疗方式。经过对BPH的病理过程和分子景观的广泛调查,现在已经认识到,不同的病理生理机制可能导致个体之间不同的BPH亚型。这种洞察力需要采用个性化的治疗策略,超越了以5-ARI为中心的普遍的一刀切的范式。早期识别容易产生治疗抵抗的个体的必要性将促使医生在未来的实践中主动分层风险并调整治疗策略。这种个性化的医疗方法标志着从目前的标准治疗模式的进步,正在成为BPH管理的未来轨迹。
    OBJECTIVE: Despite the widespread utilization of 5-alpha reductase inhibitors (5-ARIs) for managing benign prostatic hyperplasia (BPH), certain BPH patients exhibit unresponsiveness to 5-ARIs therapy. This paper provides a comprehensive overview of the current perspectives on the mechanisms of 5-ARIs resistance in BPH patients and integrates potential biomarkers and underlying therapeutic options for 5-ARIs resistance. These findings may facilitate the development of novel or optimize more effective treatment options, and promote personalized medicine for BPH.
    RESULTS: The pathways contributing to resistance against 5-ARIs in certain BPH patients encompass epigenetic modifications, shifts in hormone levels, autophagic processes, and variations in androgen receptor structures, and these pathways may ultimately be attributed to inflammation. Promisingly, novel biomarkers, including intravesical prostatic protrusion, inflammatory factors, and single nucleotide polymorphisms, may offer predictive insights into the responsiveness to 5-ARIs therapy, empowering physicians to fine-tune treatment strategies. Additionally, on the horizon, GV1001 and mTOR inhibitors have emerged as potential alternative therapeutic modalities for addressing BPH in the future. After extensive investigation into BPH\'s pathological processes and molecular landscape, it is now recognized that diverse pathophysiological mechanisms may contribute to different BPH subtypes among individuals. This insight necessitates the adoption of personalized treatment strategies, moving beyond the prevailing one-size-fits-all paradigm centered around 5-ARIs. The imperative for early identification of individuals prone to treatment resistance will drive physicians to proactively stratify risk and adapt treatment tactics in future practice. This personalized medicine approach marks a progression from the current standard treatment model, emerging as the future trajectory in BPH management.
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  • 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
    Testosterone (T) is a sex steroid hormone that often varies seasonally and mediates trade-offs between territorial aggression and parental care. Prior work has provided key insights into the \'top-down\' hypothalamic control of this seasonal plasticity in T, yet mechanisms acting outside of the brain may also influence circulating T levels. We hypothesized that peripheral mechanisms may be especially critical for females, because peripheral regulation may mitigate the costs of systemically elevated T. Here, we begin to test this hypothesis using a seasonal comparative approach, measuring gene expression in peripheral tissues in tree swallows (Tachycineta bicolor), a songbird with intense female-female competition and T-mediated aggression. We focused on the gonad and liver for their role in T production and metabolism, respectively, and we contrasted females captured during territory establishment versus incubation. During territory establishment, when T levels are highest, we found elevated gene expression of the hepatic steroid metabolizing enzyme CYP2C19 along with several ovarian steroidogenic enzymes, including the androgenic 5α-reductase. Despite these seasonal changes in gene expression along the steroidogenic pathway, we did not observe seasonal changes in sensitivity to upstream signals, measured as ovarian mRNA abundance of luteinizing hormone receptor. Together, these data suggest that differential regulation of steroidogenic gene expression in the ovary is a potentially major contributor to seasonal changes in T levels in females. Furthermore, these data provide a unique and organismal glimpse into tissue-specific gene regulation and its potential role in hormonal plasticity in females.
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  • 文章类型: Journal Article
    5-α reductase deficiency is a rare 46,XY disorder of sex development. We present detailed phenotypic and genotypic features of a cohort of 24 subjects from a highly consanguineous population of Saudi Arabia SUBJECTS AND METHODS: We studied the clinical presentation and hormonal profiles of 24 subjects diagnosed with 5-α reductase deficiency and performed genetic testing on DNA isolated from their peripheral blood using polymerase chain reaction and direct sequencing of the SRD5A2.
    All subjects had 46,XY karyotype and presented with atypical appearance of external genitalia ranging from clitoromegaly, micophallus with hypospadias, undescended testes to completely normally looking female genitalia. Thirteen (54%) of them had severe under virilization and were assigned female sex at birth. The other 11 subjects were raised as males. Stimulated Testosterone:Dihydrotestosterone ratio was high in all 16 subjects in whom it was measured. The genetic testing revealed 2 nonsense mutations (p.R103X and p.R227X) in 2 unrelated subjects, 3 missense mutations (p.P181L, p.A228T, p.R246Q) in 11 subjects and a splice site mutation (IVS1-2A > G) in 11 other subjects. There was significant phenotypic variability even in subjects with the same mutation and also within the same family.
    This is the first and largest report of the clinical and molecular genetics of 5-α reductase deficiency from the Middle East. It shows weak genotype/phenotype correlation and significant phenotypic heterogeneity. IVS1-2A > G mutation is the most common mutation and is likely to be a founder mutation in this part of the world.
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