Metabolic Clearance Rate and Urinary Clearance of Purified β-Core

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Abstract
We injected a highly purified preparation of the β-core molecule, a fragment of hCGβ excreted in pregnancy urine, into five men and three women to determine its kinetic parameters, MCR, and urinary clearance. The β-core molecule was distributed in an initial volume [1950+−156 (mean+−SEM) mL/m2 body surface area] approximately equal to the estimated plasma volume. Its disappearance was multiexponential on a semilogarithmic plot, with a rapid phase t½ of 3.5+−0.7 min and a slow phase t½ of 22.4+−4.2 min. The transit time (the mean time spent by a molecule of β-core in transit) was 20.6+−2.1 min. The MCR was 192.0+−8.0 mL/min-m2 body surface area. About 5%of the injected dose of β-core was excreted into the urine in the first 30 min after injection, and low levels of excretion persisted for up to 7 days. The urinary clearance rate of β-core was 13.7+−1.4 mL/min-m2, accounting for about 8%of the elimination of β-core from the plasma. The β-core immunoreactivity in serum and urine was characterized by gel filtration and three independent RIA systems to show that its properties were indistinguishable from those of the injected β-core. Serum levels of β-core in pregnant women were less than 0.2 ng/mL, while the amounts excreted in their urine were as much as 5mg/day. Based on these clearance parameters of β-core in normal subjects, less than 0.2%of the β-core excreted in pregnancy urine is derived by urinary clearance of plasma β-core. Therefore, more than 99%of the β-core excreted in pregnancy urine is derived from β-core in a compartment separate from plasma. In particular, these data indicate that there is relatively little placental secretion of β-core into plasma and that placental secretion does not account for the vast majority of β-core in pregnancy urine. These findings are consistent with previous data that point to renal parenchymal degradation of hCG and hCGβ as the major source of urinary β-core in pregnancy.