PMID: 7538072Apr 1, 1995Paper

Differential regulation of the cytochrome P450 3A1 gene transcription by dexamethasone in immature and adult rat liver

European Journal of Biochemistry
T M Pereira, M C Lechner

Abstract

We have previously shown that the in vivo induction of cytochrome P450 3A1 by dexamethasone occurs through a sharp and early transcriptional activation in the immature rat liver that is drastically impaired in adults [Telhada, M. B., Pereira, T. M. & Lechner, M. C. (1992) Arch. Biochem. Biophys. 298, 714-725]. In the present study we investigate the relative importance of cytochrome P450 3A1 gene transcription on the adaptive response to the synthetic glucocorticoid dexamethasone, by measuring the time-course run-on transcription rate and concomitant mRNA accumulation in the male rat liver at two different ontological developmental stages. The primary (direct) or secondary (dependent on protein neo-synthesis) nature of the in vivo inductive response to dexamethasone and to pregnenolone 16 alpha-carbonitrile, is further investigated by inhibiting translation by cycloheximide pretreatment. The induction of cytochrome P450 3A1 gene transcription by the anti-glucocorticoid pregnenolone 16 alpha-carbonitrile is demonstrated to occur through a secondary mechanism, requiring ongoing protein biosynthesis, regardless of the developmental stage of the animals. Conversely, a significant developmentally controlled change is observed in the...Continue Reading

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Citations

Nov 6, 2003·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Jeffrey F WaringRoger G Ulrich
Feb 19, 1998·DNA and Cell Biology·T M PereiraJ A Gustafsson

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