Chick embryo liver microsomal steroid hydroxylations: induction by dexamethasone, phenobarbital, and glutethimide and inactivation following the in ovo administration of porphyrinogenic compounds.
Metabolites of [4-(14)C]androstenedione (AD) and [4-(14)C]progesterone (PG) were separated and quantitated following incubation with hepatic microsomes from chick embryos. PG 2 alpha-hydroxylase and AD 7 alpha-hydroxylase, which are diagnostic markers in rat liver for cytochrome P450 (P450) 2C11 and 2A1/2, respectively, were not identified in chick embryo liver. PG 6 beta-hydroxylase and AD 6 beta-hydroxylase, diagnostic markers for P450 3A1/2 activity in rat liver, were identified in chick embryo liver, and we were able to show that radiolabeled 6 beta-hydroxyprogesterone and 6 beta-hydroxyandrostenedione, the metabolites of PG and AD 6 beta-hydroxylase, respectively, were homogeneous and identical with authentic standards. Dexamethasone, phenobarbital, and glutethimide were found to be significant inducers of PG and AD 6 beta-hydroxylases in chick embryo liver. The in ovo administration of the porphyrinogenic compounds 3,5-diethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4-ethylpyridine (4-ethyl DDC) and 3-[2-(2,4,6-trimethylphenyl)-thioethyl]-4-methylsydnone (TTMS) caused inactivation of chick embryo hepatic PG and AD 6 beta-hydroxylases. Therefore, we suggest that PG and AD 6 beta-hydroxylases may serve as diagnostic markers for a P450 3A-like isozyme in the chick embryo, and that this isozyme is one of the targets for inactivation by 4-ethyl DDC and TTMS.
Kimmett
S M
SM
Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, Canada.
McNamee
J P
JP
Marks
G S
GS
D000818:Animals; D002642:Chick Embryo; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation; D005984:Glutethimide / Q000494:pharmacology; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects*; D008861:Microsomes / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011165:Porphyrinogens / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*
D011165:Porphyrinogens; D013256:Steroids; D011374:Progesterone; D003907:Dexamethasone; D005984:Glutethimide; D010634:Phenobarbital