hCGβ core fragment is a metabolite of hCG: Evidence from infusion of recombinant hCG

Abstract

The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the β core fragment of hCG (hCGβcf). Serum and urine samples were collected from six subjects, after an intravenous injection of 2mg (equivalent to 44000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGβ). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGβcf and hCG. rmap -hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4 ± 0.71 (mean ± S.D.) and then in 6.5 ± 1.151 at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5±0.7 h and a terminal half-life of 29.0±4-6 h. The mean residence time was 28.6± 3.6 h and the total systemic clearance rate of r-hCG was 226 ± 18 ml/h. The renal clearance rate was 28.75±6.2 ml/h (mean ± S.D.). hCGβcf was detected in all urine samples collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3%) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGβcf, in 4 subjects. The molar ratio of hCGβcf to hCG in urine increased from 3.1 ± 1.7%, on day 1, to 76±34.3% (mean ± S.E.M.) on day 5, after r-hCG infusion, suggesting that hCGβcf is a metabolic product of the infused r- hCG.