Evolutionary conservation of the sulfated oligosaccharides on vertebrate glycoprotein hormones that control circulatory half-life

The circulatory half-life of the mammalian glycoprotein hormone lutropin is controlled by its unique Asn-linked oligosaccharides, which terminate with the sequence SO₄-4-GalNAcβ1,4GlcNAc. A cluster of basic amine acids essential for recognition of the α subunit by the glycoprotein hormone:N- acetylgalactosaminyltransferase is located within two turns of an α helix (Mengeling, B. J., Manzella, S. M., and Baenziger, J. U. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 502-506). The amino acids within this region are virtually invariant in the a subunits of all vertebrates, indicating that the recognition determinant utilized by the N-acetylgalactosaminyltransferase has been conserved in species ranging from teleost fish to mammals. We demonstrate that the glycoprotein hormone:N-acetylgalactosaminyltransferase and the N-acetylgalactosamine-4-sulfotransferase responsible for the synthesis of these unique sulfated oligosaccharides are expressed in the pituitaries of vertebrates ranging from teleost fish to mammals. Furthermore, we show that Asn-linked oligosaccharides terminating with SO₄-4- GalNAcβ1,4GlcNAc are present on the α and β subunits of the salmon glycoprotein hormone GTH II. Asn-linked oligosaccharides terminating with SO₄-4-GalNAcβ1,4GlcNAc are unique structural features of the glycoprotein hormones that have been conserved during vertebrate evolution, suggesting they are critical for the expression of hormone biologic activity.