Renal Metabolism of theβ-Subunit of Human Choriogonadotropin in the Rat

Publisher Website
Google Scholar
Abstract
We analyzed the immunoreactive renal metabolites of the .beta.-subunit moieties of unlabeled highly purified hCG, hCG.beta., and desialylated hCG (as-hCG) in rats by RIA and Sephadex G-100 chromatography. Infusions of hCG.beta., as-hCG, or intact hCG resulted in accumulation in the kidney of a large quantity of small mol wt peptides lacking the immunological determinants of the carboxy-terminal peptide (CTP) of the .beta.-subunit. In the case of as-hCG, renal accumulation of these .beta.-core fragments was greatly enhanced when as-hCG binding to hepatic galactose receptors was inhibited by infusion of asfetuin. The .beta.-core fragments in kidney had the same immunological and G-100 chromatographic characteristics as .beta.-core fragments in liver, suggesting similar intracellular catabolic mechanisms in these tissues. The kinetics of .beta.-core fragment turnover in kidney were studied after injection of hCG.beta., which is cleared from the circulation within 1 h. Loss of .beta.CTP immunoreactivity was the initial event in hCB.beta. catabolism by the kidney; most of this process occurred between 7 and 30 min after injection. This was followed by a gradual reduction of the size of accumulated hCG.beta. metabolites over the next 60 min. The .beta.-core fragments that accumulated had a Kav of approximately 0.57 and a very slow degradation rate over the next 5 h (half-life > 6 h). Chromatographic analysis of urine obtained 6 h after beginning a continuous infusion of hCG, hCG.beta., or as-hCG displayed in each case a major peak corresponding to the infused molecule, apparently intact, and a minor peak of .beta.CTP immunoreactivity of small mol wt. Relative to the .beta.CTP fragments apparent in urine, there were few .beta.-core fragments. These data indicate that separate fates exist for immunoreactive fragments generated by hCG.beta. metabolism in the rat kidney. One appears to be intracellular and similar to the liver pathway of as-hCG degradation in that it leads to the formation of long-lived .beta.-core fragments. The other takes place within ready access to the urinary compartment and leads to the accumulation in urine of .beta.-CTP fragments.

This publication has 18 references indexed in Scilit: