Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, 6th Floor-SiMR Building, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand.
J Biol Inorg Chem. 2019 Oct;24(7):973-983. doi: 10.1007/s00775-019-01692-z. Epub 2019 Jul 24.
Finasteride (a 5α-reductase inhibitor) has been widely used for treatment of several testosterone-related disorders. However, its beneficial role in kidney stone disease had not been previously investigated. This study thus addressed whether finasteride has any protective effects against testosterone-induced calcium oxalate monohydrate (COM) kidney stone formation. Renal tubular cells were treated with testosterone with/without finasteride for 72 h. Western blotting revealed the increased level of α-enolase (a known COM crystal receptor) in whole-cell lysate, apical membrane, and cytosolic fraction of the testosterone-treated cells. Immunofluorescence staining also showed the increased levels of surface and intracellular α-enolase in the testosterone-treated cells. In addition, testosterone significantly increased the number of adherent COM crystals on the cell surface. All of these effects were completely abolished by finasteride treatment. Interestingly, the secreted proteins from testosterone-treated cells significantly increased COM crystallization, but did not affect crystal growth and aggregation. Again, such promoting effect of testosterone on COM crystallization was completely abolished by finasteride. These data indicate that finasteride effectively protects testosterone-induced kidney stone formation by restoring apical surface expression of α-enolase and COM crystal-cell adhesion to their basal levels. Moreover, finasteride can also neutralize the promoting effect of testosterone on COM crystallization.
非那雄胺（一种 5α-还原酶抑制剂）已被广泛用于治疗多种与睾酮相关的疾病。然而，其在肾结石疾病中的有益作用尚未得到先前的研究。因此，本研究旨在探讨非那雄胺是否对睾酮诱导的一水合草酸钙（COM）肾结石形成具有保护作用。将肾小管细胞用睾酮和/或非那雄胺处理 72 小时。Western blot 显示，全细胞裂解物、顶膜和胞质部分中α-烯醇酶（已知的 COM 晶体受体）的水平增加。免疫荧光染色也显示，在睾酮处理的细胞中，α-烯醇酶的表面和细胞内水平增加。此外，睾酮显著增加了 COM 晶体在细胞表面的黏附数量。所有这些作用均被非那雄胺完全消除。有趣的是，来自睾酮处理细胞的分泌蛋白显著增加了 COM 的结晶，但不影响晶体的生长和聚集。同样，非那雄胺完全消除了睾酮对 COM 结晶的促进作用。这些数据表明，非那雄胺通过恢复顶膜表面α-烯醇酶的表达和 COM 晶体-细胞黏附至基础水平，有效保护睾酮诱导的肾结石形成。此外，非那雄胺还可以中和睾酮对 COM 结晶的促进作用。
