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Genetic and hormonal regulation of steroid hydroxylases and drug metabolizing enzymes in rat liver

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Abstract

Two microsomal steroid hydroxylase activities (cholesterol-7α-hydroxylase and progesterone-16α-hydroxylase) were measured in the livers of Sprague-Dawley and Wistar rats and compared to three other monooxygenase activities (aryl hydrocarbon hydroxylase, p-nitro-anisole-O-demethylase and aminopyrine-N-demethylase). Cholesterol-7α-hydroxylase behaves in a very unique manner. It is the only one of the studied enzymes to be more active in the female than in the male, it is very poorly induced by phenobarbital and methylcholanthrene, but responds quickly to the administration of glucocorticoids. In fact, the cholesterol-7α-hydroxylase activity presents a very pronounced circadian rhythm which is under the control of the hypothalamo-adrenal axis. Marked differences are also found in the response of the various enzymatic activities to the administration of inducers as well as in their relative activities in untreated male and female animals.

Zusammenfassung

Zwei mikrosomale Steroidhydroxylase-Aktivitäten (Cholesterin-7α-hydroxylase und Progesteron-16α-hydroxylase) wurden in Lebern von Sprague-Dawley und Wistar-Ratten gemessen und mit drei anderen Monooxygenase-Aktivitäten (Aryl hydrocarbon hydroxylase, p-Nitro-anisol-O-demethylase und Aminopyrin-N-demethylase) verglichen.

Cholesterin-7α-hydroxylase weist ein besonderes Verhalten auf. Es ist das einzige der untersuchten Enzyme, welches bei weiblichen Tieren stärker aktiv ist als bei männlichen Tieren, das durch Phenobarbital und Methylcholanthren nur sehr wenig induziert wird, aber sehr schnell auf die Verabreichung von Glucocorticoiden reagiert. Die Cholesterin-7α-hydroxylase Aktivität weist einen stark ausgeprägten circadianen Rhythmus auf, welcher ja durch die Hypothalamoadrenale-Achse kontrolliert wird.

Ausgeprägte Unterschiede werden auch in der Reaktion der verschiedenen enzymatischen Aktivitäten auf die Verabreichung von Induktoren festgestellt, wie auch in ihren relativen Aktivitäten bei unbehandelten männlichen und weiblichen Tieren.

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Authors and Affiliations

  1. Unité de Biochimie, Laboratoire de Chimie Médicale, Institut de Pathologie, B-4000, Sart-Tilman par Liège 1, Belgium

    Jacques E. Gielen, Jacques Van Cantfort & Pierre Kremers

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  1. Jacques E. Gielen
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  2. Jacques Van Cantfort
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  3. Pierre Kremers
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Read at the Symposium “Relevance of Chronobiology for Toxicology and Pharmacology” held at the 16th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Section: Toxicology, March 6, 1975, Mainz

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Gielen, J.E., Van Cantfort, J. & Kremers, P. Genetic and hormonal regulation of steroid hydroxylases and drug metabolizing enzymes in rat liver. Arch. Toxicol. 36, 255–266 (1976). https://doi.org/10.1007/BF00340533

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  • DOI: https://doi.org/10.1007/BF00340533

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