Inhibition of estrogen 2-hydroxylase.

The effect of diethylstilbestrol (DES), oestradiol (E2), primaquine (PQ), chloroquine (CQ), 1-methylimidazole (1-MeI), metronidazole (MET) and antipyrine (AP) has been studied on rat liver microsomal metabolism of ethinyloestradiol (EE2) by measuring the formation of 2-hydroxyethinyl-oestradiol (2-OHEE2) using reverse phase high performance liquid chromatography. Using a substrate concentration of 25 microM, PQ, DES and E2 produced the most marked effect with IC50 values of 75, 100 and 100 microM respectively whereas CQ, MET and 1-MeI were less potent with IC50 values of 335, 448 and 448 microM. AP inhibited EE2 metabolism to only a small extent and an IC50 value was not calculated. PQ (75 microM) inhibited the enzyme non-competitively decreasing the Vmax from 1.8 to 1.0 nmol/min/mg protein. E2 (100 microM) inhibited the enzyme competitively with an increase in the Km from 17.9 to 55.6 microM. The results of this study indicate that steroidal and non-steroidal compounds have different affinities for EE2 2-hydroxylase.