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Influence of Various Estrogens on Biotransformation: Affinity to Cytochrome P‐450, Structure Activity Relationships, and Scavenger Function
Author(s) -
Gernhardt Sabine,
Karge Elke,
Schönecker Bruno,
Klinger Wolfgang
Publication year - 1997
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19973300505
Subject(s) - chemistry , ethylmorphine , cytochrome , monooxygenase , microsome , ether , cytochrome p450 , demethylation , hydroxylation , biotransformation , ethinylestradiol , metabolite , metabolism , stereochemistry , microsoma , biochemistry , enzyme , organic chemistry , population , gene expression , demography , sociology , dna methylation , research methodology , gene
Nine natural and synthetic estrogens, all derived from endogenous 17β‐estradiol, were tested for their affinity to cytochrome P‐450 (P450). Binding spectra of the estrogens with rat liver microsomal P450 and inhibition kinetics with characteristic monooxygenase model reactions (ethylmorphine N ‐demethylation, EN, and ethoxycoumarin O ‐deethylation, EO) were determined. In addition, uncoupling effects and/or free radical scavenger functions were analysed by NADPH/Fe ++ stimulated microsomal luminol‐and lucigenin‐amplified chemiluminescense (CL). 17β‐Estradiol, 17α‐ethynylestradiol, and D‐estradiol 3‐methyl ether inhibited both monooxygenase reactions of cytochrome P‐450, whereas L‐estradiol 3‐methyl ether inhibited EO only. 17β‐Estradiol, 17α‐ethynylestradiol, and D‐estradiol 3‐methyl ether seem to act as free radical scavengers. From the results both structure activity relationships could be established and data on possible interferences with drug metabolism obtained. The enantiomers D‐ and L‐estradiol 3‐methyl ether differ in their effects on these systems.