Sex-related differences in the expression of cytochrome P450 in hamsters: cDNA cloning and examination of the expression of three distinct CYP2C cDNAs.
Sex-related differences in the expression of cytochrome P450 isozymes in hamsters were investigated. Three distinct cDNA clones (assigned as CYP2C25, CYP2C26, and CYP2C27) were isolated from liver cDNA libraries from male and female hamsters, using rat CYP2C11 cDNA as a probe. Sequence analysis revealed that these three forms were very similar to each other (> 90% identity of nucleotide sequences) and belong to the CYP2C gene subfamily. The CYP2C25, CYP2C26, and CYP2C27 cDNA clones consisted of an open reading frame encoding 490 amino acids. CYP2C25, CYP2C26, and CYP2C27 proteins expressed in Saccharomyces cerevisiae catalyzed the hydroxylation of tolbutamide and the N-demethylation of aminopyrine and benzphetamine. Only CYP2C25 showed testosterone hydroxylase (16 beta) activity. Northern blot analyses with specific oligonucleotide probes demonstrated that expression of CYP2C27 was male specific and male predominant in kidneys and livers, respectively. No sex-related difference was observed in the expression of CYP2C25 and CYP2C26. These results support our previous findings that sex-related differences in the expression of liver microsomal cytochromes P450 occur in hamsters.
Sakuma
T
T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Masaki
K
K
Itoh
S
S
Yokoi
T
T
Kamataki
T
T
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001589:Benzphetamine / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry / Q000145:classification / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D018076:DNA, Complementary / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006900:Hydroxylation; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D016415:Sequence Alignment; D012727:Sex Characteristics; D014044:Tolbutamide / Q000378:metabolism
D018076:DNA, Complementary; D015345:Oligonucleotide Probes; D000632:Aminopyrine; D001589:Benzphetamine; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; C086043:CYP2C25 protein, Mesocricetus auratus; C086044:CYP2C26 protein, Mesocricetus auratus; C086045:CYP2C27 protein, Mesocricetus auratus; D000072467:Cytochrome P450 Family 2