Equine lutropin and chorionic gonadotropin bear oligosaccharides terminating with SO₄-4-GalNAc and Siaα2,3Gal, respectively

Equine chorionic gonadotropin (eCG) and lutropin (eLH) are heterodimeric glycoprotein hormones which are synthesized in the placenta and pituitary, respectively The β subunits of eCG and eLH, like their α subunits, arise from a single gene and have identical amino acid sequences. In contrast, the β subunits of CG and LH in primates arise from different genes and differ in sequence. We have examined the structures of the Asn-linked oligosaccharides on eCG and eLH. eCG bears di- and tri-branched Asn-linked oligosaccharides terminating with Siaα2,3 or 6Galβ1,4GlcNAc. In contrast, >72% of the Asn-linked oligosaccharides on eLH have 1 or 2 branches terminating with the sequence SO₄-4-GalNAcβ1,4GlcNAc. The nonsulfated oligosaccharides on eLH are neutral (6% of the total) or have branches terminating with sialic acid-Gal (22% of the total). Since the α and β subunits of eCG and eLH both contain the tripeptide motif, Pro-Xaa-Arg/Lys, recognized by the glycoprotein hormone-specific GalNAc-transferase found in pituitary, expression of the GalNAc- and sulfotransferases must differ in the placenta and pituitary. eLH, but not eCG, is bound by the hepatic endothelial cell receptor specific for the sequence SO₄-4-GalNAcβ1,4GlcNAc. As a result, eLH is removed from the circulation 5.7-fold more rapidly than eCG and is selectively localized to the liver. Since the major structural difference between eCG and eLH is in the terminal glycosylation of their Asn-linked oligosaccharides and this has a major impact on circulatory half-life, it is likely that the difference in circulatory half-life defines the functional difference between eCG and eLH.