Metabolism of catechol estrogens by erythrocyte catechol-O methyltransferase.

Fishman and Tulchinsky (1) present evidence that the catechol estrogen 2hydroxyestrone suppresses serum prolactin in normal ovulatory young women. However, in 3 of the 12 subjects studied the authors were unable to suppress serum prolactin and suggested that prolactin response to 2-hydroxyestrone is subjectand not time-dependent. In a study designed to evaluate the kinetics of catechol estrogen formation from plasma estrone in vivo, Bates et al. (2) were unable to compute the transfer constant of conversion of estrone to 2hydroxyestrone because of intravascular metabolism of 2-hydroxyestrone by erythrocytes. During the infusion, the radioactively labeled 2-hydroxyestrone was metabolized to its methyl ether, 2methoxyestrone, by erythrocyte catechol-O-methyltransferase (COMT). This finding led to the development of a radioenzymatic assay for quantifying COMT in erythrocytes with the use of radioactively labeled 2-hydroxyestrone as the substrate (3). Weinshilboum et al. (4) have demonstrated a bimodal distribution of COMT activity in erythrocytes from 373 randomly selected young men and women. We have not identified a bimodal distribution of COMT activity in our investigations, but we have found increased COMT activity in erythrocytes of pregnant women (5), in women with pregnancy-induced hypertension, and in fetal blood (6). We suggest that the three subjects studied by Fishman and Tulchinsky who failed to have prolactin suppression may have increased erythrocyte COMT activity. This could result in intravascular metabolism of 2-hydroxyestrone before the infused material reached its site of action. We further suggest that measurement of erythrocyte COMT activity should be part of the investigation of catechol estrogen infusion studies. G. WILLIAM BATES EUGENE JACKSON, JR. University of Mississippi Medical Center, Jackson, Mississippi 39216