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A second female-predominant murine CYP3A, CYP3A44, was isolated from liver and its mRNA expression was compared with that of the previously described CYP3A41. The expression of CYP3A44 was relatively constant after birth in females, whereas it gradually declined in males after 5 weeks of age. The expression of CYP3A41 increased with age in females after 3 weeks of age, whereas it gradually declined in males after 5 weeks of age. Hypophysectomy and growth hormone replacement indicated that expression of both CYP3A mRNAs in females was dependent on the feminine plasma growth hormone profile. Estradiol induced the expression of both mRNAs and the effect was dependent on the presence of the pituitary gland. These observations suggest that endocrine control of expression might be similar, but not identical, for two female-predominant CYP3A mRNAs., (Copyright 2002 Elsevier Science (USA).)

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 16alpha-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., (Copyright 2000 Academic Press.)

The effect of the synthetic glucocorticoid, dexamethasone, and phenobarbital upon the expression of Cyp2b9 and Cyp2b10, major CYP2B subfamilies in the mouse, was differentiated in C57BL/6 mouse liver and hepatocytes in primary culture. Overall expression was higher in the untreated female liver than in the male liver. More Cyp2b9 than Cyp2b10 mRNA was present in the female liver, whereas the level of Cyp2b10 was higher in the male. Phenobarbital increased Cyp2b10 expression more than did Cyp2b9 in both sexes. Treatment with dexamethasone markedly induced Cyp2b10 expression dose dependently, but simultaneously suppressed Cyp2b9 in both sexes. Evidence of this was obtained both in vivo and in hepatocyte culture. Furthermore, the existence of at least two unknown species of CYP2B, whose expressions were either increased or decreased by dexamethasone was suggested. Adrenalectomy increased the expression of Cyp2b9 and Cyp2b10 mRNAs, especially that of Cyp2b9 in the male liver. In addition, the expression of one unknown species which was constitutively suppressed increased in adrenalectomized male mice. That the treatment of dexamethasone or adrenalectomy altered the expression of CYP2B subfamilies suggests that endogenous glucocorticoid hormone plays a basic role in the constitutive expression of cytochrome P450. Furthermore, the sex-related difference in the expression of Cyp2b9 and Cyp2b10 suggests that sex-dependent secretion of endogeneous modulating factors is involved in the regulatory pathway., (Copyright 1999 Academic Press.)