Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Steroids. 2011 Feb;76(3):301-8. doi: 10.1016/j.steroids.2010.12.001. Epub 2010 Dec 13.
The mechanism accounting for the development of castration-resistant prostate cancer (CRPC) remains unclear. Studies in CRPC tissues suggest that, after androgen deprivation therapy (ADT), the adrenal androgens may be an important source of testosterone (T) and 5-alpha dihydrotestosterone (DHT) in CRPC tissues. To clarify the role of adrenal androgens in the prostatic tissues (prostatic tissue adrenal androgens) during ADT, we developed a high sensitive and specific quantification method for the levels of androgens in prostatic tissue using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Human prostatic tissues were purified using mixed-mode reversed-phase, strong anion exchange Oasis cartridges (Oasis MAX). Analysis of steroids was performed using LC-MS/MS after picolinic acid derivatization. The validation tests showed that our method of quantitative analysis was precise and sensitive enough for the quantification of dehydroepiandrosterone (DHEA), androstenedione, androstenediol, T, and DHT in the prostatic tissue. The levels of adrenal androgens in prostate cancer tissues after ADT were similar to those in untreated PCa. Especially, DHEA was the most existing androgen precursor in PCa tissues after ADT. The levels of DHEA were high in PCa tissues, irrespective of ADT. We assumed that DHEA played a significant role in the synthesis of T and DHT in PCa tissues after ADT.
导致去势抵抗性前列腺癌（CRPC）发展的确切机制尚不清楚。在 CRPC 组织中的研究表明，在去势治疗（ADT）后，肾上腺雄激素可能是 CRPC 组织中睾酮（T）和 5-α 二氢睾酮（DHT）的重要来源。为了阐明 ADT 期间前列腺组织中肾上腺雄激素的作用（前列腺组织肾上腺雄激素），我们使用液相色谱-串联质谱（LC-MS/MS）开发了一种用于检测前列腺组织中雄激素水平的高灵敏度和特异性定量方法。使用混合模式反相、强阴离子交换 Oasis 试剂盒（Oasis MAX）对人前列腺组织进行纯化。用 picolinic 酸衍生化后，使用 LC-MS/MS 进行类固醇分析。验证测试表明，我们的定量分析方法足够精确和灵敏，可用于定量分析前列腺组织中的脱氢表雄酮（DHEA）、雄烯二酮、雄烯二醇、T 和 DHT。ADT 后前列腺癌组织中的肾上腺雄激素水平与未经治疗的 PCa 相似。特别是，DHEA 是 ADT 后 PCa 组织中存在的最主要雄激素前体。DHEA 在 PCa 组织中的水平较高，与 ADT 无关。我们假设 DHEA 在 ADT 后 PCa 组织中 T 和 DHT 的合成中发挥重要作用。
