Further studies on the persistence of neonatal androgen imprinting on sex-specific cytochrome P-450, testosterone and drug oxidations

M. Shimada, N. Murayama, Y. Yamazoe, T. Kamataki, R. Kato

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    23 Citations (Scopus)

    Abstract

    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, testosterone 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 O-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. At 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.

    Original languageEnglish
    Pages (from-to)467-478
    Number of pages12
    JournalJapanese Journal of Pharmacology
    Volume45
    Issue number4
    Publication statusPublished - 1987

    ASJC Scopus subject areas

    • Pharmacology

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