Tracing steroidogenesis in prostate biopsy samples to unveil prostate tissue androgen metabolism characteristics and potential clinical application
Tracing steroidogenesis in prostate biopsy samples to unveil prostate tissue androgen metabolism characteristics and potential clinical application
复制标题
DOI：
10.1016/j.jsbmb.2021.105859
复制
发表时间：
2021-03-19
影响因子：
4.1
通讯作者：
Li, Zhenfei
中科院分区：
文献类型：
--
作者：
Hou, Zemin;Yang, Tao;Li, Zhenfei
雄激素对于前列腺癌的发展是必不可少的。然而，类固醇激素的生成主要是在数量有限的前列腺癌细胞系中进行的研究，导致了不同的结论和难以捉摸的临床意义。在这里，我们建立了一个体外研究平台，将新鲜的活检标本与三种标记的雄激素瞬时培养，以追踪前列腺组织中类固醇的生成，并探讨其潜在的临床应用。脱氢表雄酮被确认为前列腺雄激素合成的主要前体。在前列腺活检样本中，DHEA产生了大量的氧化型DHEA和5-α-雄二酮。前列腺类固醇激素的生成不受其他临床因素的影响。此外，去雄激素治疗后，前列腺类固醇激素的生成受到抑制，但在治疗耐药时增加，这表明临床治疗对前列腺类固醇激素的生成有影响。总体而言，我们提供了一个可访问的研究平台来表征前列腺组织中的类固醇激素生成，并指出前列腺类固醇激素生成与疾病进展之间的相关性。
Androgens are essential for prostate cancer development. However, steroidogenesis has mainly been investigated in a limited number of prostate cancer cell lines, leading to varied conclusions and elusive clinical significance. Here, we established an ex vivo research platform with fresh biopsy samples transiently cultured with tritiumlabelled androgens to trace steroidogenesis in prostate tissues and investigate its potential clinical application. DHEA was confirmed as the major precursor for androgen synthesis in the prostate. Significant amounts of oxidized DHEA and 5 alpha-androstanedione were generated from DHEA in prostate biopsy samples. Prostatic steroidogenesis was independent of other clinical factors. Furthermore, prostatic steroidogenesis was suppressed after androgen deprivation therapy but increased upon treatment resistance, indicating that prostatic steroidogenesis was affected by clinical treatments. Overall, we provide an accessible research platform to characterize steroidogenesis in prostate tissue and indicate the correlation between prostatic steroidogenesis and disease progression.