Steroid metabolism & the chimeric mouse model

01 January 2010 → 31 December 2012
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Medical and health sciences
    • Laboratory medicine
    • Laboratory medicine
    • Laboratory medicine
Steroid metabolism
Project description

The aim of the project was to study the metabolism of different steroid compounds by means of a humanized chimeric mouse model. This uPA+/+-SCID mouse model has its liver transplanted with functional human hepatocytes. In the past the chimeric mouse model has proven to be a valuable tool in elucidating the urinary steroid metabolism, especially for those steroids for which it is difficult to obtain ethical approval for human excretion studies.

In this project the metabolism of 7
steroid compounds was investigated:
* methyl-1-testosterone
* oxabolone
* prostanozol
* 6-bromo-androstenedione
* 3 α-androstanol
* 17-methyldrostanolone
* 4-chloro-17-methylandrostenediol (promagnon and methylclostebol)

The metabolism of these 7 steroids was investigated by use of administration studies to the
chimeric mouse model. The analyses of the mouse urine samples were performed on a
combination of GC-MS and LC-MS/MS instruments. Comparing the pre- and post-administration
mouse urine samples allowed us to obtain a urinary metabolic profile for all of the steroids. From all the detected metabolites, the most appropriate markers were selected based on their usefulness as target markers for steroid abuse. Those metabolites were implemented where possible in our routine screening methods for anti-doping screening, making our methods even more complete and comprehensive. Additionally, within the scope of the project, also the in vitro technique of human liver microsomes was optimized to assist this research. In the future this promising mouse model will be used to further encourage the fight against doping by evaluating some prohormones and food supplements based on the urinary results of the chimeric mice