Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of norethindrone (NEI), norethandrolone (NEA), and ethinyl estradiol (EE) on liver cytochrome P-450 in rats were studied. Rats were pretreated with phenobarbitone sodium (80 mg/kg for 3 days), 3-methyl cholanthrene (20 mg/kg for 3 days), and pregnenolone 16alpha-carbonitrite (75 mg/kg twice daily for 3 days). NEI, NEA, and EE were given at a dose of 100 mg/kg. Liver microsomal fractions were prepared and determinations of cytochromes P-450 and b5 made. Steroids were also incubated with liver mitochondrial preparations and P-450 measured. Liver porphyrins were determined as were mitochondrial 5-aminolaevulinate synthase activity. Isolation of green pigments was undertaken. NEI and EE caused a time-dependent loss of cytochrome P-450 when incubated in vitro with rat microsomal fractions and NADPH-generating systems. The effect of pretreatment of rats with inducers of mixed-function oxidases on the steroid mediated loss of cytochrome P-450 in vitro were: 1) phenobarbitone stimulated P-450 breakdown, 2) methylcholanthrene-induced cytochrome P-448 was unaffected, and 3) pregnenolone was without effect. The enzyme system involved in the NEI breakdown of P-450 has many of the characteristics of the microsomal mixed-function oxidases. In vivo, there was a marked decrease in P-450 (52%) after a single injection of NEI. Cytochrome b5 was minimally affected. Loss of P-450 was accompanied by increasing porphyrin levels. NEI, NEA, and EE caused a 3.2-fold induction of 5-aminolaevulinate synthase activity. Rats pretreated with phenobarbitone and given NEI or EE formed green pigments. While metabolic pathways differ between the species, it is suggested that long-term estrogen therapy might predispose some individuals to the type of porphyria associated with the side effects of these compounds.
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PMID:Decreased liver cytochrome P-450 in rats caused by norethindrone or ethynyloestradiol. 90 18