A novel female-specific member of the CYP3A gene subfamily in the mouse liver

Expression of a female-specific CYP3A in the adult mouse liver was observed on immunoblotting analysis. To characterize this cytochrome P450, we deter mined 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 3A 25, respectively, and was designated as CYP3A41, a new mouse CYP3A gene. In the female liver, levels of CYP3A41 mRNA expression were comparable to tho se of CYP3A11, the major CYP3A enzyme in the adult mouse liver. Expression of CYP3A41 mRNA was detected immediately after birth in the livers of anima ls of both sexes, but increased with age in females, whereas it was gradual ly reduced in males, resulting in predominantly female-specific expression in livers. Lesser amounts of CYP3A41 mRNA were detected in the kidneys of f emale mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice. Gonadectomy and sex hormone treatment indicate d that estradiol and testosterone were able to induce and suppress the expr ession of CYP3A41 mRNA in the liver, respectively. Among the classical CYP3 A inducers, dexamethasone, rifampicin, and 3-methylcholanthrene did not aff ect the level of CYP3A41 mRNA in the liver of either sex. On the other hand , pregnenolone 16 alpha-carbonitrile and phenobarbital suppressed CYP3A41 l evel to half that of untreated female mice. These observations indicated th at CYP3A41 is a female-specific CYP3A and one of the major CYP3A forms in t he female mouse liver. (C) 2000 Academic Press.