Department of Clinical Chemistry, Microbiology and Immunology, Doping Control Laboratory (DoCoLab), Ghent University, Technologiepark 30, Zwijnaarde, Belgium.
Drug Test Anal. 2009 Nov;1(11-12):531-7. doi: 10.1002/dta.67.
Anabolic androgenic steroids are considered to be doping agents and are prohibited in sports. Their metabolism needs to be elucidated to allow for urinary detection by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Steroid metabolism was assessed using uPA(+/+) SCID mice with humanized livers (chimeric mice). This study presents the results of 19-norandrost-4-ene-3,17-dione (19-norAD) administration to these in vivo mice. As in humans, 19-norandrosterone and 19-noretiocholanolone are the major detectable metabolites of 19-norAD in the urine of chimeric mice.A summary is given of the metabolic pathways found in chimeric mice after administration of three model steroid compounds (methandienone, androst-4-ene-3,17-dione and 19-norandrost-4-ene-3,17-dione). From these studies we can conclude that all major metabolic pathways for anabolic steroids in humans are present in the chimeric mouse. It is hoped that, in future, this promising chimeric mouse model might assist the discovery of new and possible longer detectable metabolites of (designer) steroids.
合成代谢雄激素类固醇被认为是兴奋剂，在体育运动中被禁止使用。为了通过气相色谱-质谱联用（GC-MS）或液相色谱-串联质谱（LC-MS/MS）进行尿液检测，需要阐明其代谢情况。使用具有人源化肝脏（嵌合小鼠）的 uPA(+/+) SCID 小鼠评估了类固醇代谢。本研究介绍了将 19-去甲雄-4-烯-3,17-二酮（19-norAD）施用于这些体内小鼠的结果。与人类一样，19-去甲雄酮和 19-去甲雄烷醇酮是嵌合小鼠尿液中 19-norAD 的主要可检测代谢物。总结了在给予三种模型类固醇化合物（美雄酮、雄烷-4-烯-3,17-二酮和 19-去甲雄-4-烯-3,17-二酮）后，嵌合小鼠中发现的代谢途径。从这些研究中可以得出结论，人类中所有用于合成代谢类固醇的主要代谢途径都存在于嵌合小鼠中。希望未来，这种有前途的嵌合小鼠模型能够帮助发现（设计）类固醇的新的和可能更长时间可检测的代谢物。
