Influence of Various Estrogens on Biotransformation: Affinity to Cytochrome P-450, Structure Activity Relationships, and Scavenger Function
✍ Scribed by Sabine Gernhardt; Elke Karge; Bruno Schönecker; Wolfgang Klinger
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 488 KB
- Volume
- 330
- Category
- Article
- ISSN
- 0365-6233
No coin nor oath required. For personal study only.
✦ Synopsis
Nine natural and synthetic estrogens, all derived from endogenous 17P-estradio1, 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 0-deethylation, EO) were determined. In addition, uncoupling effects and/or free radical scavenger functions were analysed by NADPH/Fe++ stimulated microsomal luminoland lucigenin-amplified chemiluminescense (CL). 17P-Estradio1, 17a-ethynylestradiol, and D-estradiol 3-methyl ether inhibited both monooxygenase reactions of cytochrome P-450, whereas L-estradiol3-methyl ether inhibited EO only. 17P-Estradio1, 17aethynylestradiol, and D-estradiol3-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-estra-diol3-methyl ether differ in their effects on these systems.