A B S T R A C T The continuous infusion of 3H-6,7-estrone and 3H-6,7-estradiol has been used to study the metabolic clearance rate (MCR), the interconversions, and the red cell uptake of these steroids in normal males and females. The whole blood MCR of estrone is 1,990 + 120 liters per day/ m2 (SE) in males and 1,910 + 100 liters per day/M2 in females. The whole blood MCR of estradiol is 1,600 + 80 liters per day/M2 in males and 1,360 + 40 liters per day/M2 in females. The values in females do not vary significantly when studied in the follicular or luteal phase of the cycle. At least 35%o of the total estrone metabolism in both sexes is extrasplanchnic and at least 25%o of the total estradiol metabolism in males, and 15%o in-females is extrasplanchnic. The [p] BB21 [transfer constant of estradiol. to estrone, which is equivalent to the fraction of the precursor (estradiol) converted to the product (estrone) when both the infusion of the precursor and the measurement of the product aire in peripheral blood] is 15%o; and the [p]BB"2 [transfer constant of estrone to estradiol, which is equivalent to the fraction of the precursor (estrone) converted to product (estradiol) when both the infusion of the precusor and the measurement of the product are in peripheral blood] is 5%o in both
INTRODUCTIONThe metabolic clearance rate (MCR) of a substance, defined as that volume of blood from which it is totally and irreversibly cleared in unit time, is a concept which has been applied to studies of the metabolism of aldosterone, cortisol, progesterone, and the androgens (1-5). In this manner, information has been obtained concerning splanchnic and extrasplanchnic metabolism. In addition, the use of the continuous infusion technique has provided data on the interconversion of androstenedione and testosterone (3,4,6) and on the uptake of steroid hormones into red cells (2).Previous studies of the metabolism of estrone and 17,8-estradiol in nonpregnant humans have provided some data concerning the half-lives of these steroids in plasma (7) and the red cell binding of estrone (8). The major studies have been concerned with urinary metabolites and with the radioactivity appearing in these metabolites after administration of the labeled hormone (9-11). In-The Journal of Clinical Investigation Volume 47 1968 93 formation obtained in this manner however does not always reflect the dynamics of the circulating hormone (4, 12, 13). Therefore, we felt that a study of the metabolic clearance rates and the interconversion of estrone and 17fl-estradiol in blood would provide a fuller picture of the metabolism of these steriods. The plasma MCR of testosterone is much lower than the hepatic plasma flow. This difference indicates incomplete splanchnic extraction for this steroid (3,4,6). However, the plasma MCR of androstenedione is greater than hepatic plasma flow (3, 4, 6). Bardin and Lipsett (13) have reported that the plasma MCR of testosterone is greater for males than for females, and the difference is significant after correction...