Tissue and sex-dependent differences in CYP2A activities in hamsters.
Three enzymatic activities of the CYP2A subfamily, coumarin 7-hydroxylase (COH), testosterone 15 alpha-hydroxylase (T15 alpha OH) and testosterone 7 alpha-hydroxylase (T7 alpha OH), were characterized in liver, kidney and lung microsomes from control, pyrazole (PYR), 3-methylcholanthrene (MC) and phenobarbital (PB) treated female and male Syrian golden hamsters. Sex-dependent changes in the enzymatic activities were found. Among control animals COH and T15 alpha OH activities were higher in males. T7 alpha OH activity was five times higher in female kidneys than in males. Inducers changed this metabolic profile. MC and PB were potent CYP2A inducers in extrahepatic tissues: significant increases were found in COH (5-fold) and T15 alpha OH (12-fold) activities in female MC lung microsomes and T7 alpha OH (7-fold) in MC male kidney microsomes. PB increased significantly activities of COH (5-fold), T15 alpha OH (3-fold) and T7 alpha OH (10-fold) in male kidney microsomes. All inducers significantly increased T7 alpha OH activity in male kidney microsomes but decreased hepatic T7 alpha OH activity in both sexes. PYR treatment decreased hepatic CYP2A activities. Anti-mouse CYP2A4/5 antibody inhibited COH activity by a variable extent depending on the tissue and pretreatment and recognised three 52-, 49-, 48-kDa bands in liver and two major bands in kidney (48 and 49 kDa) and lung (49 and 52 kDa) microsomes. COH and T15 alpha OH activities correlated well with 49 kDa protein (r = 0.95 and r = 0.99, respectively) in lung microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)
Pelkonen
P
P
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Lang
M
M
Pasanen
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D006224:Cricetinae; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D015151:Immunoblotting; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000378:metabolism*
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; C050356:steroid 15-alpha-hydroxylase; C022724:testosterone 7-alpha-hydroxylase, hamster