Abstract：
:This study examines strain differences in testosterone (T)-hydroxylations between Wistar and Dark Agouti (DA) rats of both genders. The DA rat, an animal model, is a poor metabolizer of such drugs as debrisoquine, which are metabolized by cytochrome P450 (CYP) 2D. T-16α-, 2α-hydroxylations, which are linked to CYP2C11, were catalyzed at similar rates by the microsomes of both strains. In contrast, the liver microsomes from mature male DA rats catalyzed T-6β-hydroxylation, the CYP3A mediated activity, at higher rates (∼ 2-fold) than Wistar rat liver microsomes did. There was no difference between immature male DA and Wistar rats for T-6β-hydroxylation, indicating that the activity in male DA rat increases with maturation. Polyclonal antibodies raised against rat liver microsomal CYP3A2 and a CYP3A inhibitor, troleandomycin (TAO), effectively inhibited T-6β-hydroxylation by liver microsomes from both strains of rats. The level of T-6β- hydroxylation activity correlated well with the amount of CYP3A protein in the microsomes in mature as well as in immature male and female Wistar and DA rats. Northern blot analysis repeatedly indicated that the cellular contents of CYP3A2 mRNA are slightly (∼ 20%) higher in the liver of mature DA rats than in that of mature Wistar rats. These results indicate that the increased levels of CYP3A are responsible for the increased T-6β-hydroxylation activity and protein in DA rat.
journal_name
Environ Toxicol Pharmacoljournal_title
Environmental toxicology and pharmacologyauthors
Maeda Y,Morita K,Tasaki T,Kazusaka A,Imaoka S,Funae Y,Fujita Sdoi
10.1016/s1382-6689(96)00130-5subject
Has Abstractpub_date
1997-02-15 00:00:00pages
1-6issue
1eissn
1382-6689issn
1872-7077pii
S1382-6689(96)00130-5journal_volume
3pub_type
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journal_title：Environmental toxicology and pharmacology
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更新日期：2020-11-01 00:00:00
