The role of glycosylation in regulating the glycoprotein hormone free alpha-subunit and free beta-subunit combination in the extraembryonic coelomic fluid of early pregnancy.

Abstract

The extra-embryonic coelom (EEC) and secondary yolk sac are prominent structures in the gestational sac during the first trimester of human pregnancy, at a time before the definitive placenta] circulation becomes established. We propose that the EEC and yolk sac play a critical role in the nutrition of early pregnancy, fulfilling exchange functions which are assumed by the placenta at a later stage.

Hormone-Specific Inhibitory Influence of α-Subunit Asn56 Oligosaccharide on In Vitro Subunit Association and Follicle-Stimulating Hormone Receptor Binding of Equine Gonadotropins1

“…As free hCGa Asn 5 2 is decorated with all three types of oligosaccharide (unpublished results), this degree of subunit combination probably reflects association of the biantennary oligosaccharide population. PNGase digestion of free hCGa increased the dimerization efficiency of the deglycosylated a derivative to 64% [47] by removing Asn 5 2 oligosaccharides [50]. Our data are consistent with these results, as the highest efficiency of equine gonadotropin subunit dimerization was obtained with monoantennary oligosaccharides attached to eLHa Asn 5 6 .…”

“…Free hCGa carbohydrate obtained from both glycosylation sites included biantennary, triantennary, and tetraantennary oligosaccharides [49]. While the association efficiency for the combination of hCGa with hCG3 was 73%, increased oligosaccharide branching of free hCGa carbohydrate resulted in a lower dimerization efficiency of 14% [47]. As free hCGa Asn 5 2 is decorated with all three types of oligosaccharide (unpublished results), this degree of subunit combination probably reflects association of the biantennary oligosaccharide population.…”

Solution structure of the α‐subunit of human chorionic gonadotropin

“…Besides the role of αhCG in the αβ‐dimer it has been discovered that the noncombined α‐subunit of hCG (hCG‐α f ), which is produced in significant amounts by the placenta during pregnancy, is able to stimulate prolactin secretion from human decidual cells [42,43]. Although the carbohydrate composition of hCG‐α f partially differs from αhCG [43,44], the α‐subunit derived through dissociation of hCG is also able to stimulate prolactin secretion cells [42]. This observation strongly indicates that the solution structure of dg‐αhCG is almost identical to that of fully glycosylated hCG‐α f .…”

Mammalian protein glycosylation – structure versus function

“…This site-specic glycosylation is required for efficient recombination of both a and b subunits to form the active hormone. 165 One should also mention the laborious work on the glycosylation of Tamm-Horsfall glycoprotein, 166 where only one (N14) out of eight potential sites was non-occupied, and the rest exhibited remarkable diversity: the N489 site included di-and tri-charged oligosaccharides exposing, among others, the 4HSO 3 -Gal-NAc(b1-4)GlcNAc epitope; N251 contained only oligomannosetype chains ranging from Man 5 GlcNAc 2 to Man 8 GlcNAc 2 , while N208 was quite heterogeneous, with multiply charged complex glycan structures terminated by sulfate groups, Sia residues, and/or the Sd a -determinant. A nal example is human erythropoietin (EPO), possibly the most extensively studied cytokine, for which full glycan proling (of the endogenous form) is, aer nearly 50 years of research effort, still incomplete.…”