Human chorionic gonadotropin, its receptor and mechanism of action

Human chorionic gonadotropin (HCG) is a glycoprotein hormone consisting of two noncovalently bonded subunits, alpha and beta. The hormone can be dissociated and reassociated. Whereas the individual subunits do not show any receptor binding activity, the reconstituted molecule is almost fully active. The amino acid and carbohydrate sequences in hCG-alpha and hCG-beta are described. There are in all seven carbohydrate units, four complex asparagine-linked and three serine-linked short oligosaccharide chains. The sequential removal of monosaccharides from the carbohydrate moiety of the hormone results in derivatives that bind to the cell surface receptors but inhibit the hCG-induced accumulation of cAMP. The derivatives, however, still are able to produce steroidogenesis maximally. The data raise the possibility of other mediator(s) of the hormone action in addition to cAMP. The hCG/LH (luteinizing hormone) receptor has been labeled by the incorporation of N-acetyl-D-1-[14C] glucosamine and also by the selective incorporation of 125I or 131I. Using 131I-labeled bovine corpus luteal plasma membranes, a method for the purification of the receptor to homogeneity has been developed. The purified receptor has properties similar to the membrane-bound receptor. Availability of the purified receptor offers newer approaches to the study of molecular mechanisms of polypeptide hormone action.