Open AccessA hepatocarcinogenic tryptophan–pyrolyzate component, Trp‐P‐1, decreases serum total testosterone level and induces hepatic Cyp1a2 in male mice
Author(s) -
Degawa Masakuni,
Hanaki Koji,
Sekimoto Masashi
Publication year - 2006
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2006.00140.x
Subject(s) - medicine , endocrinology , cyp1a2 , chemistry , testosterone (patch) , cytochrome p450 , cholesterol side chain cleavage enzyme , metabolism , biology
Male (BALB/c × DBA/2) F 1 mice were given 3‐amino‐1,4‐dimethyl‐5 H ‐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, 3β‐hydroxysteroid dehydrogenase and steroid 17α‐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. ( Cancer Sci 2006; 97: 32–37)