Role of carbohydrates in glycoprotein hormone signal transduction

Abstract

The structure of the polypeptide chains and oligosaccharide moieties of the a and β subunits of pituitary and placental glycoprotein hormones are known. The dimeric polypeptide structure (but not the carbohydrate) is important for binding of the hormone to specific receptors. The N‐linked but not O‐linked carbohydrates, on the other hand, are required in some manner to activate the effector system. Hormones with depleted carbohydrate content (deglycosylated hormones) interact with receptor but are unable to activate intracellular events. Because of such discordant properties, these forms act as competitive inhibitors of hormone action. Through a combination of chemical deglycosylation procedures and site‐directed mutagenesis, the first site of N‐glycosylation from the NH 2 terminus of the common α subunit has been identified to be most critical for glycoprotein hormone signal transduction. Control of glycosylation by the endocrine milieu could contribute to regulation of hormone function by secreting variable forms of agonist/antagonist.— S airam , M. R. Role of carbohydrates in glycoprotein hormone signal transduction. FASEB J. 3: 1915‐1926; 1989.