Research Center, Hellenic Anticancer Institute, Athens, Greece.
J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Dec 1;940:24-34. doi: 10.1016/j.jchromb.2013.09.022. Epub 2013 Sep 27.
Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC-MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC-MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.
乳腺和前列腺是具有强烈甾体生成活性的器官。临床和流行病学数据为雄激素和雌激素对典型激素依赖性恶性肿瘤（如乳腺癌和前列腺癌）风险的影响提供了强有力的证据。最近的研究集中在雄激素代谢物在调节激素敏感组织中雄激素浓度方面的作用。甾体葡萄糖醛酸化被认为在控制未结合雄激素的水平和生物学活性方面具有突出作用。已确立的是，雄激素葡萄糖醛酸酯的血清水平反映了雄激素敏感组织中的雄激素代谢。定量分析血液标本中的雄激素代谢物是唯一一种微创方法，可以准确估计雄激素的总池。在过去的几年中，雄激素葡萄糖醛酸酯分析最常涉及放射免疫分析（RIA）或直接免疫分析，这两种方法都存在严重的局限性。然而，近年来质谱技术的显著技术进步，特别是液相色谱与质谱联用（LC-MS/MS），克服了这些缺点，使得即使在低浓度下也能同时、定量地分析多种类固醇。通过 LC-MS/MS 进行血液雄激素分析，一种具有高选择性、灵敏度、特异性、精密度和准确性的可靠技术，作为人类病理学研究的一种有前途的新方法出现。本综述通过应用 LC-MS/MS 提供了雄激素葡萄糖醛酸酯分析的最新见解，强调了在类固醇研究及其在激素依赖性恶性肿瘤中的作用方面的新观点。
