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.

Abstract

Abstract-P-450-male is one of the male-specific forms of cytochrome P-450 in liver microsomes of adult rats and functions as testosterone 2a and 1 6a-hydroxy lases. 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 micro somes 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 nitro cellulose 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 2a-hydroxylase in male rats, 1 6a-hydroxy lase in male rats and male and female dogs, 7a-hydroxylase in female rats and male and female mice and hamsters, and 15a-hydroxylase in female mice and hamsters. No clear inhibition of 6i3-hydroxylase, which was present in all animal species, was observed.These results indicate that forms of cytochrome P-450 that are im munochemically related with P-450-male catalyze the hydroxylation of testosterone at varying positions depending on the animal species, with the exception of 6(3 hydroxylation, which may be catalyzed by a distinct form of cytochrome P-450.

Metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes

“…The 6b-hydroxylase activities, which was the major testosterone hydroxylase in rats, hamsters, and male and female humans, were 1.1, 7.2, 4.6 and 7.4 nmol/min per mg microsomal protein, respectively. These results agree approximately with those of experimental data published in literature (Miura et al 1988;Miura et al 1989;Imaoka et al 1989), although the activities in humans varied among individuals. The hepatic microsomes used here were therefore considered to have normal enzymatic activity.…”

In vitro metabolism of testosterone in the horse liver and involvement of equine CYPs 3A89, 3A94 and 3A95

“…It has many advantages including its good stability and the fact that a number of different CYPs metabolize TES to several metabolites making it a convenient ‘starting substance’ when nothing is known about substrate specificity of CYPs in a species. TES is metabolized in vitro to a variety of metabolites, predominantly products hydroxylated at different positions of the ring system (Ford et al ., ; Miura et al ., ).…”