Effect of 17 alpha-ethynylestradiol on the induction of cytochrome P-450 by 3-methylcholanthrene in cultured chick embryo hepatocytes. 1988

S A Sundstrom, and J F Sinclair, and E L Smith, and P R Sinclair
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03756.

This study investigated the effects of estrogens on the induction of cytochrome P-450 by polycyclic aromatic hydrocarbons in primary cultures of chick embryo hepatocytes. Exposure to polycyclic aromatic hydrocarbons, such as 3-methylcholanthrene led to 2- to 3-fold increases of cytochrome P-450. The amount of cytochrome P-450 induced by 3-methylcholanthrene was increased 40-50% when the synthetic estrogen, 17 alpha-ethynylestradiol, was also present. The rate of decay of cytochrome P-450 in the presence of cycloheximide as measured spectrophotometrically was similar in cells previously treated with either 3-methylcholanthrene or 3-methylcholanthrene plus 17 alpha-ethynylestradiol, suggesting that 17 alpha-ethynylestradiol did not affect the stability of the 3-methylcholanthrene-induced cytochrome P-450. In contrast, 17 alpha-ethynylestradiol did not potentiate the induction of cytochrome P-450 by phenobarbital-like inducers, such as 2-propyl-2-isopropylacetamide, as indicated by a lack of increase in both the content of cytochrome P-450 and benzphetamine demethylase activity. The naturally occurring estrogens, 17 beta-estradiol and estrone, and the synthetic estrogen, diethylstilbestrol, did not affect cytochrome P-450 induction by 3-methylcholanthrene, suggesting that the effect of 17 alpha-ethynylestradiol was not mediated via the estrogen receptor. We investigated whether the amount of cytochrome P-450 increased in the presence of 17 alpha-ethynylestradiol was the same or different from that induced by 3-methylcholanthrene. Treatment with 17 alpha-ethynylestradiol alone resulted in a small increase in ethoxyresorufin deethylase activity. The enzymatic activities of 7-ethoxyresorufin and aryl hydrocarbon hydroxylase, when expressed per cytochrome P-450 content, were identical in microsomes from cells treated with either 3-methylcholanthrene or the combination of 3-methylcholanthrene and 17 alpha-ethynylestradiol. The data suggest that the additional cytochrome P-450 induced by the combination of 17 alpha-ethynylestradiol and 3-methylcholanthrene was the same isozyme as that induced by 3-methylcholanthrene alone.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008748 Methylcholanthrene A carcinogen that is often used in experimental cancer studies. 20-Methylcholanthrene,3-Methylcholanthrene,20 Methylcholanthrene,3 Methylcholanthrene
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D011164 Porphyrias A diverse group of metabolic diseases characterized by errors in the biosynthetic pathway of HEME in the LIVER, the BONE MARROW, or both. They are classified by the deficiency of specific enzymes, the tissue site of enzyme defect, or the clinical features that include neurological (acute) or cutaneous (skin lesions). Porphyrias can be hereditary or acquired as a result of toxicity to the hepatic or erythropoietic marrow tissues. Porphyria,Porphyrin Disorder,Disorder, Porphyrin,Disorders, Porphyrin,Porphyrin Disorders
D011955 Receptors, Drug Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified. Drug Receptors,Drug Receptor,Receptor, Drug
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D003907 Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug

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