Biogenesis of Catecholestrogens: A Mechanism for Metabolic Activation of Estrogens

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Abstract
Catecholestrogens (CE) are products of aromatic hydroxylation at C−2 or C−4 of primary estrogens and their synthetic steroidal agonists. CE are generated in a number of target organs where they may act as. local mediators of estrogen action. They have also been implicated in carcinogenesis, since CE are substrates for redox cycling and hence, a potential source of free radicals. Biogenesis of CE can occur via two mechanisms, one monooxygenase and the other peroxidative. These two mechanisms have different implications for estrogen action because of differences in their co−factor requirement and in the amounts of 2− and 4−hydroxylated estrogens they generate. This review focuses on the phase I enzymes, the cytochromes P450 that catalyze 2− and 4−hydroxylation of estrogens, on the distinctive properties of 2− and 4−OHCE and on the phase II enzymes responsible for their inactivation.

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