Characterization of a Discrete Degradation Product of the Human Chorionic Gonadotropin β-Subunit in Humans

We have investigated the different forms of immunoreactive hCGβ excreted in the urine of normal volunteers after iv administration of highly purified hCG β-subunit. Chromatography of urine on Sephadex G-100 revealed two discrete peaks ofhCGβ immunoreactivity as measured with antiserum to hCGβ (SB6). The material of larger apparent molecular weight appeared to be hCGβ itself, since it eluted from the column in the same position as authentic hCGβ, contained full hCGβ carboxy-terminal peptide immunoreactivity, adsorbed to Concanavalin A, and gave a dose-response curve parallel to hCGβ in the hCGβ RIA. The other form of immunoreactive hCGβ eluted from the column as a separate, discrete peak in a positioncorresponding to a molecular weight about 25% that of authentic hCGβ. This hCGβ fragment gave a dose-response curve parallel to hCGβ in the hCGβ RIAand adsorbed to Concanavalin A but appeared to lack an intact hCGβ carboxyterminal peptide immunological determinant. After a single iv injection of hCGβ, the time course of the excretion of the hCGβ fragment was delayed relative to that of intact hCGβ more than 90% of the hCGβ immunoreactivity excreted during the first 4 h after injection was intact hCGβ, but after 12 h, more than 90% of the hCGβ immunoreactivity in the urine was hCGβ fragment. We conclude that a metabolic pathway exists in humans which degrades the hCG β-subunit to a discrete carbohydrate-containing fragment with an apparent molecular weight about 25% that of the hCG β-subunit.