Inhibition of dihydropteridine reductase by catechol estrogens.
Catechol estrogens, such as 2-hydroxyestriol, 2-hydroxyestradiol, and 2-hydroxyestrone, inhibit human liver dihydropteridine reductase noncompetitively with Ki values ranging from 1.5 to 4.6 X 10(-6)M. Catechol estrogens lose approximately half of their inhibitory potency if the C-2 hydroxyl groups are methylated. Thus, 2-methoxyestrogens have inhibitory potencies equivalent to those of their parent estrogens--estriol, estradiol, and estrone. Aromatization of ring B or stereoisomerism at C-17 does not affect the inhibitory potency of estrogens, although stereoisomerism at C-16 enhances the inhibitory potency of estriol. These results support the hypothesis that catechol estrogens may interfere with catecholamine metabolism by acting as inhibitors of enzymes involved in catecholamine metabolism, such as dihydropteridine reductase.[1]References
- Inhibition of dihydropteridine reductase by catechol estrogens. Shen, R.S., Abell, C.W. J. Neurosci. Res. (1983) [Pubmed]
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