Glycoprotein hormones: glycobiology of gonadotrophins, thyrotrophin and free alpha subunit

Abstract

Chorionic gonadotrophin and pituitary luteinizing hormone, follicle-stimulating hormone and thyroid-stimulating hormone comprise the family of glycoprotein hormones, which regulate major metabolic and reproductive functions of the body. These are heterodimeric glycoproteins composed of a common alpha subunit and a hormone-specific beta subunit. The N-linked oligosaccharides of these hormones are necessary for proper folding, assembly, secretion, metabolic clearance and biological activity. The free alpha subunit, which is shown to have a physiological function, is maintained in the uncombined form due to its glycan structures. The N-glycans of the glycoprotein hormones contain a variety of terminal residues, which are responsible for the differential targeting and clearance of the hormones. Glycosylation of these hormones is regulated by a variety of physiological and pathological conditions, leading to subtle alterations in their bioactivities. Recent studies on the structures and specific functions of different glycans of natural and recombinant glycoprotein hormones have provided valuable insight into the glycobiology of these hormones. This information will be useful in the development of diagnostic and therapeutic applications of the glycoprotein hormones.