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The plasma metabolic clearance rate (MCRp) of 2-hydroxyestrone was measured in normal young adults by two methods: infusion of unlabeled 2-OHE1 to equilibrium with radioimmunoassay of plasma 2-OHE1 levels, and infusion of [3H]2-OHE1 to equilibrium with measurement of chromatographically purified plasma [3H]2-OHE1. MCR's were 40--70,000 L/day and 15--50,000 L/day, respectively. This is the highest known MCR for a naturally occurring steroid. The only measurable plasma metabolite of [3H]2-OHE1 co-migrated with 2-methoxyestrone. When [3H]2-OHE1 was incubated with blood samples in vitro, [3H] xi-methoxyestrone was rapidly formed. Since this MCR is higher than cardiac output, clearance must occur primarily in the blood compartment, probably largely by the action of erythrocyte catechol-0-methyltransferase.
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