Characterization of Human FSH Isoforms Reveals a Nonglycosylatedβ -Subunit in Addition to the Conventional Glycosylatedβ -Subunit

Human FSH consists of a mixture of isoforms that can be separated on the basis of differences in negative charge conferred by variations in the numbers of sialic acid residues that terminate oligosaccharide branches. Western analysis of human FSH isoforms separated by chromatofocusing revealed the presence of two human FSHβ isoforms that differed in size. A low mol wt human FSHβ isoform was associated with all FSH isoform fractions. A high mol wt human FSHβ isoform was associated with the more acidic fractions and increased in relative abundance as the pI decreased. Characterization of representative human FSHβ isoforms by mass spectrometry and automated Edman degradation revealed a low mol wt isoform that was not glycosylated. A high mol wt isoform was N-glycosylated at Asn residues 7 and 24. These results indicate that pituitary human FSH consists of two classes of molecules: those that possess a nonglycosylated β-subunit and those that possess a glycosylated β-subunit. Glycoprotein hormones are known to be elliptical molecules, and the β-subunit oligosaccharides project outward from the short diameter, thereby increasing it. It is interesting to speculate that this change in shape might affect ultrafiltration rates, leading to differences in delivery rates to target tissues and elimination by filtration in the kidney.