A hepatocarcinogenic tryptophan-pyrolyzate component, Trp-P-1, decreases serum total testosterone level and induces hepatic Cyp1a2 in male mice.

Male (BALB/c x DBA/2) F(1) mice were given 3-amino-1,4-dimethyl-5H-pyrido [4,3-b] indole acetate (Trp-P-1; 20 mg/kg body weight) by gavage at 24-h intervals for 1 or 2 weeks, and the effects of Trp-P-1 on the levels of serum total testosterone and hepatic cytochrome P4501a2 (Cyp1a2) were examined. A significant decrease in serum total testosterone level was observed after treatment with Trp-P-1 for 2 weeks, but not for 1 week. Likewise, gene expression levels of testicular androgenic enzymes, including cholesterol side chain cleavage cytochrome P450, 3beta-hydroxysteroid dehydrogenase and steroid 17alpha-hydroxylase/C17-20 lyase, decreased only in the mice treated with Trp-P-1 for 2 weeks. In contrast, levels of the mRNA and apoprotein of hepatic Cyp1a2 and its enzyme activity for O-demethylation of methoxyresorufin significantly increased in the mice treated with Trp-P-1 for 2 weeks, but only a small increase was observed in mice treated for 1 week. In the present study, we demonstrate for the first time that treatment of male mice with Trp-P-1 results in a decrease in serum total testosterone level through suppression of the gene expression of testicular enzymes responsible for androgen biosynthesis, and this then leads to induction of hepatic Cyp1a2.