Further Studies on the Persistence of Neonatal Androgen Imprinting on Sex-Specific Cytochrome P-450, Testosterone and Drug Oxidations
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概要
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Neonatal castration completely suppressed the expression of P-450 male and expressed P-450-female; and testosterone treatment in a neonatal period partially reversed the effect of castration, i.e., neonatal imprinting (Kamataki et al., 1984; Waxman et al., 1985). In the present communication, we investigate the reversibility and persistency of neonatal imprinting on the expression of P-450-male and P-450-female. To our surprise, testostrone treatment at adulthood (8 weeks old) caused full expression of P-450-male and restored the activities of 2α and 16α-testosterone hydroxylases in neonatally castrated rats. The levels of ethyl morphine N-demethylation, propoxycoumarin 0-depropylation and benzo(a)pyrene hydroxylation were increased to the levels of adult male rats by adult testosterone treatment. Moreover, treatment with testosterone of neonatally castrated rats at the age of 19 weeks did not cause a complete recovery of P-450-male content and drug-metabolizing activities. Testosterone administration into neonatal female rats did not significantly alter the contents of sex-dependent cytochrome P-450 and drug and steroid metabolizing activities in adulthood. Additional testosterone treatment in adulthood only slightly affected these parameters. All these results indicate that neonatal androgen imprinting on sex-dependent cytochrome P-450 and drug and steroid metabolizing activities in rat liver microsomes is not a permanent programming process and is modified by the presence and absence of sex steroid hormones.
著者
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Murayama Norie
Department Of Pharmacology School Of Medicine Keio University
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YAMAZOE YASUSHI
Department of Pharmacology, School of Medicine, Keio University
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Kato Ryuichi
Department Of Biology Graduate School Of Science Osaka University
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Yamazoe Yasushi
Department Of Pharmacology School Of Medicine Keio University
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Shimada Miki
Department Of Clinical Pharmacy Tohoku University Graduate School Of Pharmaceutical Sciences
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MURAYAMA Norie
Department of Pharmacology, School of Medicine, Keio University
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KAMATAKI Tetsuya
Department of Analytical Bio chemistry, School of Pharmacy, Hokkaido University
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KAMATAKI Tetsuya
Department of Analytical Biochemistry, School of Pharmaceutical Sciences, Hokkaido University
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YAMAZOE Yasushi
Department of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
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