Human Chorionic Gonadotropin

Abstract

Human chorionic gonadotropin (hCG) is a glycoprotein composed of two dissimilar subunits, α- and β-subunit, held together by charge interactions. hCG is produced by trophoblastic cells of the placenta in both pregnancy and gestational trophoblastic diseases. It is a remarkable glycoprotein in that up to 35% of the molecular weight (MW) is from oligosaccharide side chains. hCG is sometimes considered a mucopolysaccharide, like collagen, because of the large carbohydrate component. There is wide variation in hCG structure throughout normal and abnormal pregnancies, and in gestational trophoblastic diseases. In addition to “regular” hCG (hCG with intact subunits and the midtrimester pregnancy-like complement of oligosaccharides), at least six other key variants are present in serum samples: hyperglycosylated hCG, nicked hCG, hCG missing the β-subunit C-terminal peptide, free β-subunit, hyperglycosylated free β-subunit, and nicked free β-subunit as well as multiple combinations of these variants (i.e., nicked hyperglycosylated hCG missing the β-subunit C-terminal peptide). The same seven molecules plus the β-core fragment can be detected in urine samples (1–9). Table 1 and Fig. 1 summarize the structures of these key hCG-related molecules, which vary in size from β-core fragment (MW 9000–10,000) to hyperglycosylated hCG (MW 38,00042,000). hCG and related molecules may vary widely in charge because of differences in sialic acid content. As shown in Fig. 2, multiple charge isoforms in the range pI 3–7 are found in serum and urine samples, and in the range of pI 3–8 in hyperglycosylated hCG.