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Gene Review:

Cyp2d9 - cytochrome P450, family 2, subfamily d,...

Mus musculus

Synonyms: CYPIID9, Cyp2d, Cyp2d-9, Cytochrome P450 2D9, Cytochrome P450-16-alpha, ...

Hernandez, J.P. et al., Harada, N. et al., Hayashi, S. et al., Noshiro, M. et al., Park, S.H. et al., et al.

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High impact information on Cyp2d9

Antibody purified with the Sepharose 4B conjugate from mixed antiserum to P-450(16) alpha and P-450(15) alpha specifically inhibited testosterone 16 alpha-hydroxylase activity in microsomes [1].
By contrast, the loss of STAT5b feminized the livers of males by decreasing expression of male-specific CYPs (CYP2D9 and testosterone 16alpha-hydroxylase) while increasing to female levels several female-predominant liver CYPs (CYP3A, CYP2B, and testosterone 6beta-hydroxylase) [2].
Nuclear localization of Stat5b correlates with the repression of Cyp2a4 and expression of Cyp2d9, respectively [3].
In ERalpha-deficient males, the Cyp2d9 gene continued to be expressed [3].
In contrast Cyp2a5, Cyp2b10 and Cyp2d9 expression were elevated [4].

Biological context of Cyp2d9

Testosterone hydroxylation was also altered in a gender-specific manner, as testosterone 16alpha-hydroxylase activity was only induced in NP-treated males [5].
With the use of 19 mouse X hamster somatic cell hybrids, the db1 and db2 genes were localized to mouse chromosome 15 (P450-2D locus) [6].

Anatomical context of Cyp2d9

The antibody inhibited propranolol ring-hydroxylase and imipramine 2-hydroxylase activities, as well as testosterone 16alpha-hydroxylase activity, a typical reaction of mouse CYP2D9, but not debrisoquine 4-hydroxylase activity in mouse liver microsomes [7].
In order to examine the identity of cholecalciferol 25-hydroxylase and testosterone 16 alpha-hydroxylase, monoclonal antibodies recognizing three different epitopes of P-450cc25 were prepared from hybridoma clones produced by fusion of mouse myeloma cells (P3X63Ag8U1) with the spleen cells of immunized BALB/c mouse [8].

Associations of Cyp2d9 with chemical compounds

A cDNA fragment up-regulated by sho-saiko-to was isolated and characterized. cDNA sequencing and subsequent database analysis revealed that the fragment showed significant sequence similarity with mouse testosterone 16-alpha-hydroxylase (cytochrome P-450[16alpha]) cDNA [9].
Using specific testosterone 16 alpha-hydroxylase activity as the basis for selection of fractions during purification, the cytochrome P-450 ("I"-P-450(16)alpha) has been isolated from livers of phenobarbital-treated 129/J female mice [K. Devore, N. Harada, and M. Negishi (1985) Biochemistry, 24, 5632-5637] [10].

Regulatory relationships of Cyp2d9

An additional gene (Cyp2d9) was shown to be down-regulated in wild-type mice but up-regulated in PPARalpha-null mice indicating more complex regulation by PPARalpha and additional factors [11].

References

Sex-dependent expression of mouse testosterone 16 alpha-hydroxylase (cytochrome P-450(16) alpha): cDNA cloning and pretranslational regulation. Harada, N., Negishi, M. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
Distinctive roles of STAT5a and STAT5b in sexual dimorphism of hepatic P450 gene expression. Impact of STAT5a gene disruption. Park, S.H., Liu, X., Hennighausen, L., Davey, H.W., Waxman, D.J. J. Biol. Chem. (1999) [Pubmed]
Developmental action of estrogen receptor-alpha feminizes the growth hormone-Stat5b pathway and expression of Cyp2a4 and Cyp2d9 genes in mouse liver. Sueyoshi, T., Yokomori, N., Korach, K.S., Negishi, M. Mol. Pharmacol. (1999) [Pubmed]
Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1alpha)-deficient mice. Cheung, C., Akiyama, T.E., Kudo, G., Gonzalez, F.J. Biochem. Pharmacol. (2003) [Pubmed]
Gender-specific induction of cytochrome P450s in nonylphenol-treated FVB/NJ mice. Hernandez, J.P., Chapman, L.M., Kretschmer, X.C., Baldwin, W.S. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
Debrisoquine 4-hydroxylase: characterization of a new P450 gene subfamily, regulation, chromosomal mapping, and molecular analysis of the DA rat polymorphism. Gonzalez, F.J., Matsunaga, T., Nagata, K., Meyer, U.A., Nebert, D.W., Pastewka, J., Kozak, C.A., Gillette, J., Gelboin, H.V., Hardwick, J.P. DNA (1987) [Pubmed]
Selective deficiency of debrisoquine 4-hydroxylase activity in mouse liver microsomes. Masubuchi, Y., Iwasa, T., Hosokawa, S., Suzuki, T., Horie, T., Imaoka, S., Funae, Y., Narimatsu, S. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
Immunochemical evidence for the catalysis of vitamin D3 25-hydroxylation and testosterone 16 alpha-hydroxylation by homologous forms of cytochrome P-450 in rat liver microsomes. Hayashi, S., Omura, T., Watanabe, T., Okuda, K. J. Biochem. (1988) [Pubmed]
Long-term administration of "sho-saiko-to" increases cytochrome P-450 mRNA level in mouse liver. Kojima, K., Mizukami, H., Tazawa, T., Nose, M., Inoue, M., Ogihara, Y. Biol. Pharm. Bull. (1998) [Pubmed]
Female-predominant expression of testosterone 16 alpha-hydroxylase ("I"-P-450(16)alpha) and its repression in strain 129/J. Noshiro, M., Serabjit-Singh, C.J., Bend, J.R., Negishi, M. Arch. Biochem. Biophys. (1986) [Pubmed]
Role of the peroxisome proliferator-activated receptor alpha in responses to diisononyl phthalate. Valles, E.G., Laughter, A.R., Dunn, C.S., Cannelle, S., Swanson, C.L., Cattley, R.C., Corton, J.C. Toxicology (2003) [Pubmed]

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