Species differences of testosterone 16-hydroxylases in liver microsomes of guinea pig, rat and dog.
1. In hepatic microsomes, remarkable species differences in the activity of testosterone 16-hydroxylase was observed in guinea pig, dog, and rat. The activity of testosterone 16 beta-hydroxylase was higher than that of 16 alpha-hydroxylase in guinea pig, whereas 16 alpha-hydroxylated testosterone was predominant as the metabolite in dog and rat. 2. Since P4502B isoenzyme has been shown to be a catalyst for testosterone 16-hydroxylations, we compared the catalytic properties of the P4502B subfamily (P450GP-1, P450b and P450PBD-2) purified from liver microsomes of guinea pig, dog, and rat, respectively. P450GP-1, P450b and P450PBD-2 showed different stereoselectivities for hydroxylation of testosterone at the 16-position. 3. P450GP-1, P450b and P450PBD-2 together comprised 47, < 0.1 and 23% of total P450 in liver microsomes of untreated guinea pig, rat and dog, respectively, indicating that the amounts of the P4502B isoenzyme in untreated animals were clearly different in these three animal species. Both 16 alpha- and 16 beta-hydroxylations of testosterone in liver microsomes of phenobarbital-treated guinea pig, rat and dog were inhibited by anti-P450GP-1, anti-P450b and anti-P450PBD-2 antibodies, respectively. 4. These and other results indicate that the species difference observed in testosterone 16-hydroxylation may be, in part, due to differences in the amounts of P450 of the P4502B subfamily, and their stereoselectivities for 16-hydroxylation.
Ohmori
S
S
Laboratory of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Taniguchi
T
T
Rikihisa
T
T
Kanakubo
Y
Y
Kitada
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism*
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; C025619:steroid 16-beta-hydroxylase; C022724:testosterone 7-alpha-hydroxylase, hamster