Interspecies Homology of Cytochrome P-450: Inhibition by Anti-P-450-Male Antibodies of Testosterone Hydroxylases in Liver Microsomes from Various Animal Species Including Man

[摘要] References(44)Cited-By(7)P-450-male is one of the male-specific forms of cytochrome P-450 in liver microsomes of adult rats and functions as testosterone 2α- and 16α-hydroxylases. The purpose of this study was to examine whether forms of cytochrome P-450 cross-reactive with anti-P-450-male antibodies are present in liver microsomes of other animal species, such as male and female mice, rabbits, guinea pigs, hamsters, dogs and humans. The antibodies cross-reacted with a protein(s) in the liver microsomes of all animal species to show one or more bands on nitrocellulose paper by Western blot peroxidase-anti-peroxidase staining analysis. Qualitative as well as quantitative species differences were noted in the testosterone hydroxylases. The antibodies inhibited 2α-hydroxylase in male rats, 16α-hydroxylase in male rats and male and female dogs, 7α-hydroxylase in female rats and male and female mice and hamsters, and 15α-hydroxylase in female mice and hamsters. No clear inhibition of 6β-hydroxylase, which was present in all animal species, was observed. These results indicate that forms of cytochrome P-450 that are immunochemically related with P-450-male catalyze the hydroxylation of testosterone at varying positions depending on the animal species, with the exception of 6β-hydroxylation, which may be catalyzed by a distinct form of cytochrome P-450.

[学科分类] 药理学