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Abstract
Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH) from pituitary and chorionic gonadotropin (CG) from placenta are a family of glycoproteins, each consisting of an $\alpha$- and $\beta$-subunit. Within an animal species, the $\alpha$-subunit of all four hormones contains the identical amino acid sequence, while each $\beta$-subunit is distinct and confers biologic specificity to the hormone dimer.
Despite sharing common $\alpha$-subunits, these hormones bear Asn-linked oligosaccharides which differ in structure. The Asn-linked oligosaccharides of certain pituitary hormones, for example FSH, contain galactose and sialic acid but little or no N-acetylgalactosamine and sulfate, a pattern also seen with human CG. Other hormones, for example LH, contain little or no galactose or sialic acid, but significant amounts of N-acetylgalactosamine and sulfate.
To understand the biologic importance of the carbohydrate differences among this closely related family of proteins, I undertook a complete characterization of the structure and biosynthesis of the Asn-linked oligosaccharides on the pituitary glycoprotein hormones. LH, FSH, and TSH contain a heterogeneous array of neutral, sialylated, sulfated, and/or sialylated/sulfated Asn-linked oligosaccharides. Sulfate, when present, is linked exclusively to N-acetylgalactosamine on oligosaccharide structures which have not been encountered on other glycoproteins. Sulfated oligosaccharides are preferentially synthesized on LH and TSH, as compared to FSH. Sialic acid, when present, is linked to either galactose or N-acetylglucosamine in either $\alpha$2,3- or $\alpha$2,6-linkage. Sialylated oligosaccharides are preferentially synthesized on FSH, as compared to LH and TSH. Although the sialic acid bearing oligosaccharides are highly heterogeneous in structure, the variations tend to be hormone-specific.
The synthesis of sulfated and sialylated oligosaccharides appears to be tightly regulated. For LH and FSH which are synthesized in the same cell, the unique $\beta$-subunits appear to regulate processing of oligosaccharides present on both subunits of $\alpha$-$\beta$ dimers. The differences in oligosaccharide structures in conjunction with the highly specific endocrine-related activities of these hormones, suggest an important functional role for the oligosaccharides.
