Metabolic fate of human choriogonadotropin

Abstract

Review of the literature reveals a number of recent insights concerning the metabolic fate of human choriogonadotropin (hCG). In man, only a fraction (21.7%) of the circulating hCG molecules is excreted in urine. Results from animal studies indicate that the retained hCG is taken up by various tissues, principally kidney, liver, and ovary, where degradation occurs. Ovarian uptake is receptor mediated and saturable. Hepatic uptake of hCG is not preceded by desialylation, and blockade of hepatic receptors for galactose-terminated glycoproteins does not impair hepatic accumulation of hCG. Kidney uptake is quantitatively the most important; parenchymal metabolism, as well as excretion in urine constitute major renal components of hCG disposal. The intracellular products of hCG catabolism in kidney include certain fragments of the hCG molecule that exhibit relative resistance to processing by degradative enzymes. These products are fragments of the hCG beta subunit that lack the hCG beta carboxyterminal antigenic determinant, but retain an hCG beta core antigenic determinant, and, thus, they are designated beta-core molecules. Both kidney from hCG-infused rat and urine from pregnant women contain beta-core molecules in great abundance, in fact, in greater abundance than hCG, itself. Structural characterizations of the beta-core purified from pregnancy urine indicate a mol. wt of about 10,000 and an absence of sialic acid, galactose, and carboxyterminal peptide region, including O-linked oligosaccharides. Human volunteers given purified hCG or hCG beta by infusion excrete beta-core in their urines, which establishes the existence of catabolic pathways in humans for the production of beta-core. Thus, urinary excretion of beta-core may reflect an important fate for the metabolic products of hCG degradation.