. The glycoprotein hormone a subunit is common to the heterodi-ineric hormones CG,LH, FSH, and TSH. However, in its free form, it is an important placental and pituitary product and has been shown to have functions that are independent of the dimeric hormones. Glycosylation of free cc differs fi7om glycosylation of the combined form. The combination of cc and0 for heterodimer formation takes place in the ER prior to processing of the immature glycans. In cc subunits that have not combined with a 0 subunit, enzymes from the post-translational glycosylation machinery have access to substrate sites that are normally protected by the0 subunit of the heterodimer. As a result, the free form of oc subunit generally contains more elaborate oligosaccharide branching, as well as higher amounts of core fucosylation than a subunit obtained from dissociated hormone. These characteristic glycosylation patterns prevent secreted free (x subunits from combining with 0 subunits that might be encountered extracellularly, thus ensuring a population of free (x molecules. The (x subunit is a major placental product and its glycosylation was found to change dramatically during the advancement of pregnancy. In this collaboration, we have analyzed the glycosylation changes in five normal pregnancies. ESI NIS studies have indicated higher core-fucosylation, as well as changes in branching of glycans. The glycans were also determined by high-pH anion-exchange chromatography and CID MS/N4S. Amounts of core-fucosylation and of triantennary glycans increased substantially from early to late second trimester, and a shift was observed from 1-4/1-3 toward predom~inantly 1-6/1-6-branched triantennary structures. The glycosylation changes occurred in all individuals examined at the same gestational period, suggesting developmental regulation of N-acetylglucosaminyl-transferases IV and V, and a 6-fucosyltransferase during normal pregnancy. These enzymatic activities also appear to be affected in malignant transformation of the trophoblast. The findings have important implications for the proposed use of specific forms of glycosylation as markers for cancer, as the relative amounts of these glycans in normal pregnancy will be determined by gestational age.
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