State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China.
Department of Urology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
J Steroid Biochem Mol Biol. 2021 Jun;210:105859. doi: 10.1016/j.jsbmb.2021.105859. Epub 2021 Mar 4.
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 tritium- labelled 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 5α-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.
雄激素对于前列腺癌的发展至关重要。然而，类固醇生成主要在少数前列腺癌细胞系中进行了研究，导致了不同的结论和难以捉摸的临床意义。在这里，我们建立了一个离体研究平台，使用氚标记的雄激素对新鲜活检样本进行短暂培养，以追踪前列腺组织中的类固醇生成，并研究其潜在的临床应用。DHEA 被确认为前列腺中雄激素合成的主要前体。在前列腺活检样本中，DHEA 产生了大量氧化的 DHEA 和 5α-雄烷二酮。前列腺类固醇生成与其他临床因素无关。此外，前列腺类固醇生成在去势治疗后受到抑制，但在治疗抵抗时增加，表明前列腺类固醇生成受到临床治疗的影响。总的来说，我们提供了一个易于使用的研究平台来描述前列腺组织中的类固醇生成，并表明前列腺类固醇生成与疾病进展之间的相关性。
