Steroid metabolism in chimeric mice with humanized liver

Area of Science:

• Pharmacology
• Biochemistry
• Sports Science

Background:

• Anabolic androgenic steroids (AAS) are prohibited doping agents in sports.
• Elucidating AAS metabolism is crucial for developing effective urinary detection methods using GC-MS or LC-MS/MS.

Purpose of the Study:

• To investigate the metabolism of 19-norandrost-4-ene-3,17-dione (19-norAD) in a chimeric mouse model with humanized livers.
• To evaluate the utility of this chimeric mouse model for understanding human steroid metabolism and detecting doping agents.

Main Methods:

• Administration of 19-norAD to uPA(+/+) SCID mice with humanized livers (chimeric mice).
• Analysis of urinary metabolites using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Comparison of metabolic pathways with those observed after administration of other model steroids (methandienone, androst-4-ene-3,17-dione).

Main Results:

• 19-norandrosterone and 19-noretiocholanolone were identified as the major urinary metabolites of 19-norAD in chimeric mice, consistent with human metabolism.
• The study confirmed that chimeric mice replicate major human metabolic pathways for AAS.
• Metabolic profiles of three model steroids were summarized, demonstrating the model's applicability.

Conclusions:

• The chimeric mouse model accurately reflects human anabolic steroid metabolism.
• This model holds promise for identifying novel and potentially longer-detectable metabolites of AAS and designer steroids.
• The findings support the use of this model in anti-doping research to enhance detection capabilities.