Steroid metabolism in chimeric mice with humanized liver.
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.
Lootens
Leen
L
Department of Clinical Chemistry, Microbiology and Immunology, Doping Control Laboratory (DoCoLab), Ghent University, Technologiepark 30, Zwijnaarde, Belgium. leen.lootens@ugent.be
Van Eenoo
Peter
P
Meuleman
Philip
P
Pozo
Oscar J
OJ
Van Renterghem
Pieter
P
Leroux-Roels
Geert
G
Delbeke
Frans T
FT
D000735:Androstenedione / Q000493:pharmacokinetics*; D000818:Animals; D004300:Doping in Sports; D004963:Estrenes / Q000493:pharmacokinetics*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008696:Methandrostenolone / Q000493:pharmacokinetics*; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D015394:Molecular Structure; D010919:Placebos; D013256:Steroids / Q000493:pharmacokinetics*; D018183:Transplantation Chimera / Q000378:metabolism*
D004963:Estrenes; D010919:Placebos; D013256:Steroids; D000735:Androstenedione; D008696:Methandrostenolone