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当前对前列腺炎中雄激素信号及其治疗的理解:综述。

Current Understanding of Androgen Signaling in Prostatitis and its Treatment: A Review.

机构信息

Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Calzada del Hueso #1100, CDMX 04960, México.

出版信息

Curr Med Chem. 2024;31(27):4249-4266. doi: 10.2174/0109298673279207231228070533.

Abstract

Chronic prostatitis is a highly prevalent condition that significantly impacts the quality of life and fertility of men. Because of its heterogeneous nature, there is no definitive treatment, which requires ongoing research into its etiology. Additionally, the association between prostatitis and an elevated risk of prostate cancer highlights the importance of comprehending androgen involvement in prostatitis. This paper examines the current understanding of androgen signaling in prostatitis and explores contemporary therapeutic approaches. It was reviewed Medline articles comprehensively, using keywords such as nonbacterial prostatitis, prostatitis infertility, androgen role in prostatitis, and chronic pelvic pain. Several cellular targets are linked to androgen signaling. Notably, the major tyrosine phosphatase activity (cPAcP) in normal human prostate is influenced by androgen signaling, and its serum levels inversely correlate with prostate cancer progression. Androgens also regulate membrane-associated zinc and pyruvate transporters transduction in prostate cells, suggesting promising avenues for novel drug development aimed at inhibiting these molecules to reduce cancer tumor growth. Various therapies for prostatitis have been evaluated, including antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha-blockers, 5α-reductase inhibitors, and androgen receptor antagonists. These therapies have demonstrated varying degrees of success in ameliorating symptoms.In conclusion, aging decreases circulating T and intraprostatic DHT, altering the proper functioning of the prostate, reducing the ability of androgens to maintain normal Zn levels, and diminishing the secretion of citrate, PAcP, and other proteins into the prostatic fluid. The Zn-transporter decreases or is absent in prostate cancer, so the pyruvate transporter activates. Consequently, the cell ATP increases, inducing tumor growth.

摘要

慢性前列腺炎是一种高发疾病,严重影响男性的生活质量和生育能力。由于其异质性,目前尚无明确的治疗方法,需要对其病因进行持续研究。此外,前列腺炎与前列腺癌风险升高之间的关联突出了理解雄激素在前列腺炎中的作用的重要性。本文探讨了目前对前列腺炎中雄激素信号的理解,并探讨了当代治疗方法。本文通过使用非细菌性前列腺炎、前列腺炎不育、雄激素在前列腺炎中的作用和慢性骨盆疼痛等关键词,全面审查了 Medline 文章。雄激素信号涉及几个细胞靶标。值得注意的是,正常人类前列腺中的主要酪氨酸磷酸酶活性(cPAcP)受雄激素信号的影响,其血清水平与前列腺癌进展呈负相关。雄激素还调节前列腺细胞中膜相关锌和丙酮酸转运体的转导,这表明针对抑制这些分子以减少癌症肿瘤生长的新型药物开发具有广阔的前景。已经评估了各种前列腺炎的治疗方法,包括抗生素、抗炎药物(包括生物类黄酮)、神经调节剂、α-受体阻滞剂、5α-还原酶抑制剂和雄激素受体拮抗剂。这些治疗方法在缓解症状方面取得了不同程度的成功。总之,随着年龄的增长,循环 T 和前列腺内 DHT 减少,改变了前列腺的正常功能,降低了雄激素维持正常 Zn 水平的能力,并减少了柠檬酸盐、PAcP 和其他蛋白质分泌到前列腺液中。锌转运体在前列腺癌中减少或不存在,因此丙酮酸转运体被激活。因此,细胞 ATP 增加,导致肿瘤生长。

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