Unique carbohydrates play a central role in glycoprotein hormone function

Oligosaccharides terminating with SO₄-GalNAcβ1,4GlcNAcβ-R are present on lutropin (LH) and a limited number of other glycoproteins. The sulfated Oligosaccharides are recognized by a GalNAc-4-SO₄-specific receptor in liver and rapidly removed from the blood. The short circulatory half life is critical for producing the pulsatile rise and fall in LH which prevents down regulation of the LH/CG receptor, a G-protein coupled receptor which binds LH through its peptide and not its carbohydrate. A GalNAc-transferase, which recognizes a cluster of basic amino acids within the a subunit, and a GalNAc-4-sulfotransferase together account for the synthesis of these structures. Expression of both transferases in gonadotrophs, like LH, is modulated by estrogen in vivo. The recognition determinant is conserved on the a subunits from all vertebrates, and the GalNAc- and sulfotransferase are present within the pituitaries of all vertebrate species. The sulfated Oligosaccharides are present on fish hormones, indicating that the carbohydrate structure, like the peptide, is highly conserved. This a model system for understanding the regulation and biology of glycosylation.