Metabolic studies with promagnon, methylclostebol and methasterone in the uPA+/+-SCID chimeric mice

Abstract

The chimeric uPA(+/+)-SCID mouse model, transplanted with human hepatocytes, was previously validated as an alternative tool to study in vivo the human steroid metabolism. This humanized mouse model was now applied, in the framework of anti-doping research, to test different nutritional supplements containing steroids. These steroids, intentionally or accidentally added to a nutritional supplement, usually are derivatives of testosterone. Information about the metabolism of these derivatives, which is important to assure their detection, is quite limited. However, due to ethical constraints, human volunteers cannot be used to perform experimental excretion studies. Therefore the chimeric mice were selected to perform three separated excretion studies with superdrol (methasterone), promagnon and also methylclostebol. The urine of the humanized mice was collected 24h after a single dose administration and analyzed by gas chromatography-mass spectrometry (GC-MS). The results indicated the presence of several metabolites including a 3-keto reduced metabolite and numerous hydroxylated metabolites. Also phase 2 metabolism was investigated to update the complete picture of their metabolism.