Journal ArticleDOI
Female-predominant rat hepatic P-450 forms j (IIE1) and 3 (IIA1) are under hormonal regulatory controls distinct from those of the sex-specific P-450 forms.
TLDR
These studies demonstrate that these female-predominant hepatic P-450 enzymes are regulated by different mechanisms, and that both are under hormonal regulatory controls distinct from those that govern expression of the female-specific hepatic enzymes.Abstract:
Hepatic expression of cytochrome P-450j (alcohol- inducible nitrosamine demethylase; P-450 gene IIE1) and P- 450 3 (testosterone 7α-hydroxylase; P-450 gene IIAl) is female predominant in adult rats [female/male = 1.5-2 (P-450j) or 3-4 (P-450 3)]. This sex difference emerges during the postsuckling period, when P-450 3 declines significantly (60-70% decrease) in male, but not female, rats, and P-450j declines in both sexes, but to a lower constitutive level in males than in females. The biochemical factors and regulatory events that control these developmental changes were investigated and found to be distinct from those that regulate expression of the female-specific hepatic enzymes P-450 2d (P-450 gene IIC12) and steroid 5α-reductase. Immunoquantitation of the changes in P-450j and P- 450 3 levels in hormonally altered rats established that both P- 450s are under gonadal control. However, while androgen and estrogen both suppress P-450j expression, estrogen stimulates and androgen suppresses the expressi...read more
Citations
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Journal ArticleDOI
Bioactivation of halogenated hydrocarbons by cytochrome P4502E1.
TL;DR: Considering that metabolism governs the cytotoxicity and carcinogenicity of halogenated hydrocarbons, an understanding of the mechanism(s) underlying 2E1 induction in man becomes all the more important.
Journal ArticleDOI
Markedly enhanced cytochrome P450 2E1 induction and lipid peroxidation is associated with severe liver injury in fish oil-ethanol-fed rats.
Arnin A. Nanji,Arnin A. Nanji,Shuping Zhao,Shuping Zhao,S. M. Hossein Sadrzadeh,S. M. Hossein Sadrzadeh,Andrew J. Dannenberg,Steven R. Tahan,Steven R. Tahan,David J. Waxman +9 more
TL;DR: The results showing markedly increased CYP 2E1 induction and lipid peroxidation in the FO+E group provides one possible explanation for the greater severity of liver injury in this group of rats.
Journal ArticleDOI
Zonation of hepatic cytochrome P-450 expression and regulation
Teija Oinonen,O. Kai Lindros +1 more
TL;DR: Recent studies on the expression and induction of CYP enzymes in the perivenous region probably have important toxicological implications, since many CYP-activated chemicals cause cell injury primarily in this region of the liver.
Journal ArticleDOI
Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1
Dennis R. Koop,Daniel J. Tierney +1 more
TL;DR: Cytochrome P450IIE1 is involved in the metabolic activation of many xenobiotics involved with human toxicity and is significantly induced by the most widely abused drug in the authors' society today, alcohol.
Journal ArticleDOI
Sex-dependent expression and clofibrate inducibility of cytochrome P450 4A fatty acid omega-hydroxylases. Male specificity of liver and kidney CYP4A2 mRNA and tissue-specific regulation by growth hormone and testosterone.
TL;DR: Investigation of the contribution of pituitary-dependent hormones to the male-specific expression of 4A2 revealed that this P450 mRNA is fully suppressed in liver following exposure to the continuous plasma growth hormone profile that characterizes adult female rats, suggesting that the lower responsiveness of female rats to clofibrate-induced peroxisome proliferation may reflect the lower inducibility of the P450 4A fatty acid hydroxylase enzymes in this sex.
References
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Journal ArticleDOI
Purification and characterization of liver microsomal cytochromes p-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphthoflavone.
TL;DR: The results clearly demonstrate that individual forms of P-450 can be induced by different compounds and that a single compound can lower the level of one form of P -450 while inducing one or more other forms ofP-450.
Journal ArticleDOI
Evidence for biochemically different types of vesicles in the hepatic microsomal fraction.
Yoshio Imai,Akio Ito,Ryo Sato +2 more
Journal ArticleDOI
Sexual dimorphism in the control of growth hormone secretion.
TL;DR: A feminization of the liver develops after continuous, but not intermittent, administration of GH to hypophysectomized rats, suggesting that high, infrequent GH pulses with low plasma GH levels in between promotes growth more effectively than an intermediate, rather constant level of plasma GH.
Journal ArticleDOI
The P450 Superfamily: Updated Listing of All Genes and Recommended Nomenclature for the Chromosomal Loci
Daniel W. Nebert,David R. Nelson,Milton Adesnik,Minor J. Coon,Ronald W. Estabrook,Frank J. Gonzalez,F. Peter Guengerich,Irwin C. Gunsalus,Eric F. Johnson,Byron Kemper,Wayne Levin,Ian Phillips,Ryo Sato,Michael R. Waterman +13 more
TL;DR: A modest revision of the initially proposed nomenclature of the P450 superfamily is described specifically for the human and mouse chromosomal loci, with the root symbol "CYP" for human ("Cyp" for mouse), denoting "cytochrome P450."
Journal ArticleDOI
Regulation of rat hepatic cytochrome P-450: age-dependent expression, hormonal imprinting, and xenobiotic inducibility of sex-specific isoenzymes
TL;DR: Investigation of the influence of age, sex, and hormonal status on the expression of eight rat hepatic cytochrome P-450 (P-450) isoenzymes established that the response of these latter five isoenZymes to the P- 450 inducers phenobarbital, beta-naphthoflavone, pregnenolone-16 alpha-carbonitrile, and isosafrole is qualitatively and quantitatively equivalent in females as in males.