Ricin and lentil lectin-affinity chromatography reveals oligosaccharide heterogeneity of thyrotropin secreted by 12 human pituitary tumors.
Some patients with thyrotropin (TSH)-producing pituitary tumors are more hyperthyroid than others despite similar TSH levels in serum, suggesting that qualitatively different TSH molecules with differing bioactivities may be secreted by different tumors. We used ricin and lentil lectin-affinity chromatography to test whether the TSH oligosaccharides varied among 12 patients with TSH-producing tumors. We found that each tumor secreted heterogeneous isoforms of TSH that differed in their extents of exposed galactose (Gal) residues, and their degrees of sialylation and core fucosylation. These biochemical parameters also varied markedly for TSH secreted by different tumors. Isoforms appeared to reflect poor sialyltransferase activity in two tumors and efficient sialyltransferase in the remainder. TSH secreted by tumors was more fucosylated than TSH secreted by control euthyroid persons. There was an inverse relationship between the sialylation and fucosylation of tumor TSH. No simple relationship between TSH oligosaccharide structures and bioactivity was evident, although mixtures of isoforms having the least and most sialylated TSH seemed to be the most bioactive clinically. In three patients from whom serum and medium TSH were both available, TSH in serum was more sialylated than TSH secreted by the tumor in vitro, perhaps reflecting slow clearance of sialylated isoforms from the circulation. Core fucosylation of serum TSH was less than that of medium TSH. These data prove that human tumors secrete TSH with heterogeneous oligosaccharide structures.
Magner
J
J
Division of Endocrinology, Humana Hospital-Michael Reese, University of Illinois, Chicago 60616.
Klibanski
A
A
Fein
H
H
Smallridge
R
R
Blackard
W
W
Young
W
W
Ferriss
J B
JB
Murphy
D
D
Kane
J
J
Rubin
D
D
D000328:Adult; D002846:Chromatography, Affinity / Q000379:methods*; D005260:Female; D006801:Humans; D007536:Isomerism; D037102:Lectins; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000032:analysis*; D010911:Pituitary Neoplasms / Q000097:blood* / Q000378:metabolism; D037121:Plant Lectins; D012276:Ricin; D012799:Sialyltransferases / Q000032:analysis; D013972:Thyrotropin / Q000097:blood* / Q000737:chemistry* / Q000378:metabolism; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D037102:Lectins; D009844:Oligosaccharides; D037121:Plant Lectins; C033619:lentil lectin; D013972:Thyrotropin; D012276:Ricin; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase