engleski

Biotransformations of anabolic steroids using recombinant human CYP3A4

Two formats of human recombinant CYP3A4 have been used for in vitro study of metabolism of anabolic steroids i.e. microsomes prepared from insect cells expressing human enzyme and purified recombinant human CYP3A4 (PANVERA, USA). Structures of metabolites as trimethylsilyl-ether derivatives were determined by the GC/MS method. The reference 6beta-hydroxylated metabolites were synthesized as reported by Schanzer et al., Steroids, 60:353, 1995. After incubation of anabolic steroids with CYP3A4 enzyme systems formation of the following metabolites is suggested: STEROID METABOLITE Testosterone, 6beta-hydroxy- 17alpha-Methyltestosterone 6beta-hydroxy- Methandienone 6beta-hydroxy- 4-Chloro-1,2-dehydro-17alpha-methyltestosterone 6beta-hydroxy- Boldenone monohydroxy- (most probably 6beta-hydroxy-) 5alpha-Androstane-3alpha, 17beta-diol 5alpha-dihydrotestosterone (DHT) and monohydroxy- 5beta-Androstane-3alpha, 17beta-diol no metabolites identified 5alpha-Dihydrotestosterone (DHT) monohydroxy- Androst-4-ene-3,17-dion mono- and bishydroxy- Androst-4-ene-3beta,17beta-diol testosterone and monohydroxy- Androst-5-ene-3beta,17beta-diol no metabolites identified The results indicate that 6beta-hydroxylation is a common and preferential metabolic pathway for 3-one-, 4-ene-steroids when incubated with human CYP3A4 enzyme in vitro.

Cytochrome P450; Anabolic steroids; CYP3A4; Biotransformations; Hydroxylation

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