Evidence that Desialylation and Uptake by Hepatic Receptors for Galactose-Terminated Glycoproteins Are Immaterial to the Metabolism of Human Choriogonadotropin in the Rat

It is widely known that removal of sialic acid from the carbohydrate chains of glycoproteins in vitro drastically reduces their survival time in the circulation; however, it is not known whether desialylation plays a significant role in the metabolism of sialylated serum glycoproteins in vivo. We have studied the metabolism of hCG and desialylated hCG (as-hCG) in rat serum and liver in vivo to assess this putative metabolic pathway for glycoprotein hormones. A single injection of as-hCG into rats was followed by its rapid removal from the circulation, principally by the liver, and its degradation into fragments of the hCG beta-subunit that lacked the carboxy-terminal peptide antigenic determinant. Continuous infusion of desialylated fetuin (as-fetuin) at a high rate along with as-hCG dramatically reduced accumulation of the beta-subunit fragments in liver and resulted in increased serum levels of as-hCG. Consequently, the MCR of as-hCG was reduced from 301 +/- 10.3 ml/h (mean +/- SE) to 13.4 +/- 1.15 ml/h by infusion of as-fetuin, which is known to compete for hepatic receptors for galactose-terminated glycoproteins. In contrast, coinfusion of as-fetuin with hCG did not influence the MCR of hCG. Furthermore, there was no serum accumulation of hCG desialylated in its hCG beta carboxy-terminal portion, with or without as-fetuin, and the quantity and pattern of immunoreactive hCG products in liver homogenate were not affected by coinfusion of as-fetuin with hCG. Thus, blockade of hepatic receptors for galactose-terminated glycoproteins did not impede hCG turnover in the circulation, impair hepatic catabolism of hCG, or lead to the accumulation of desialylated products of hCG in plasma. These data indicate that in the rat, there is negligible catabolism of glycoproteins, such as hCG, by a pathway that involves peripheral desialylation and subsequent hepatic uptake via receptors for galactose-terminated glycoproteins.