Equine lutropin and chorionic gonadotropin bear oligosaccharides terminating with SO4-4-GalNAc and Sia alpha 2,3Gal, respectively.
Equine chorionic gonadotropin (eCG) and lutropin (eLH) are heterodimeric glycoprotein hormones which are synthesized in the placenta and pituitary, respectively. The beta subunits of eCG and eLH, like their alpha subunits, arise from a single gene and have identical amino acid sequences. In contrast, the beta 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 Sia alpha 2,3 or 6Gal beta 1,4GlcNAc. In contrast, > 72% of the Asn-linked oligosaccharides on eLH have 1 or 2 branches terminating with the sequence SO4-4-GalNAc beta 1,4GlcNAc. 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 alpha and beta 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-GalNAc beta 1,4GlcNAc. 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.
Smith
P L
PL
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Bousfield
G R
GR
Kumar
S
S
Fiete
D
D
Baenziger
J U
JU
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006063:Chorionic Gonadotropin / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D004727:Endothelium / Q000378:metabolism; D005260:Female; D006736:Horses; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D007986:Luteinizing Hormone / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D046911:Macromolecular Substances; D008657:Metabolic Clearance Rate; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D010902:Pituitary Gland / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats
D006063:Chorionic Gonadotropin; D046911:Macromolecular Substances; D009844:Oligosaccharides; D007986:Luteinizing Hormone