A Novel Female-Specific Member of the CYP3A Gene Subfamily in the Mouse Liver

• Published in: Archives of biochemistry and biophysics 2000-05, Vol.377 (1), p.153-162
• Main Authors: Sakuma, Tsutomu, Takai, Masae, Endo, Yusuke, Kuroiwa, Masami, Ôhara, Ayako, Jarukamjorn, Kanokwan, Honma, Rieko, Nemoto, Nobuo
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Aryl Hydrocarbon Hydroxylases; Base Sequence; Castration; Cloning, Molecular; constitutive expression; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - immunology; Cytochrome P-450 Enzyme System - metabolism; cytochrome P450; ddY; Dexamethasone - pharmacology; Estradiol - pharmacology; Female; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Expression Regulation, Developmental; Liver - cytology; Liver - enzymology; Male; Membrane Proteins; Methylcholanthrene - pharmacology; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Oxidoreductases - chemistry; Oxidoreductases - genetics; Oxidoreductases - immunology; Oxidoreductases - metabolism; Oxidoreductases, N-Demethylating - chemistry; Oxidoreductases, N-Demethylating - genetics; Oxidoreductases, N-Demethylating - metabolism; Phenobarbital - pharmacology; Pregnenolone Carbonitrile - pharmacology; RACE; Rifampin - pharmacology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sex Characteristics; Sexual Maturation; Testosterone - pharmacology
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.2000.1747

Expression of a female-specific CYP3A in the adult mouse liver was observed on immunoblotting analysis. To characterize this cytochrome P450, we determined the primary structure of its cDNA and examined its expression profile. This cytochrome P450 consisted of 504 amino acids and showed 92, 68, 88, and 69% amino acid sequence identity with mouse CYP3A11, 3A13, 3A16, and 3A25, respectively, and was designated as CYP3A41, a new mouse CYP3A gene. In the female liver, levels of CYP3A41 mRNA expression were comparable to those of CYP3A11, the major CYP3A enzyme in the adult mouse liver. Expression of CYP3A41 mRNA was detected immediately after birth in the livers of animals of both sexes, but increased with age in females, whereas it was gradually reduced in males, resulting in predominantly female-specific expression in livers. Lesser amounts of CYP3A41 mRNA were detected in the kidneys of female mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice. Gonadectomy and sex hormone treatment indicated that estradiol and testosterone were able to induce and suppress the expression of CYP3A41 mRNA in the liver, respectively. Among the classical CYP3A inducers, dexamethasone, rifampicin, and 3-methylcholanthrene did not affect the level of CYP3A41 mRNA in the liver of either sex. On the other hand, pregnenolone 16α-carbonitrile and phenobarbital suppressed CYP3A41 level to half that of untreated female mice. These observations indicated that CYP3A41 is a female-specific CYP3A and one of the major CYP3A forms in the female mouse liver.