Thyroid sialyltransferase mRNA level and activity are increased in Graves' disease.
Sialylation of cell components is an important immunomodulating mechanism affecting cell response to hormones and adhesion molecules. To study alterations in sialic acid metabolism in Graves' disease (GD) we measured the following parameters in various human thyroid tissues: lipid-bound sialic acid (LBSA) content, ganglioside profile, total sialyltransferase activity, and the two major sialyltransferase mRNAs for sialyltransferase-1 (ST6Gal I) and for sialyltransferase-4A (ST3Gal I). Fragments of toxic thyroid nodules (TN), nontoxic thyroid nodules (NN) and nontumorous tissue from patients with nodular goiter or thyroid cancer were used as a control (C). The LBSA content and sialyltransferase activity were the highest in the GD group (164 +/- 4.44 versus 120 +/- 2.00 nmoL/g, p = 0.005 and 1625 +/- 283.5 versus 324 +/- 54.2 cpm/mg of protein, p < 0.005 compared to control group C). Ganglioside profile in the GD group was similar to that in control tissues. Sialyltransferase- 1 mRNA and sialyltransferase-4A mRNA levels were significantly higher in the GD group than in the control group (12.52 +/- 6.90 versus 2.54 +/- 1.24 arbitrary units, p < 0.005 and 2,49 +/- 1.16 versus 1.23 +/- 0.46 arbitrary units, p < 0.05, respectively). There was a positive correlation between the increased sialyltransferase-1 mRNA level and the TSH-receptor antibody titer determined by the TRAK test. These results indicate that sialyltransferases expression and activity are increased in GD. Exact mechanism of this upregulation remains unknown, though one of possible explanations is the activation of the thyrotropin (TSH) receptor.
Kiljański
Jacek
J
Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland. kiljan@amwaw.edu.pl
Ambroziak
Michał
M
Pachucki
Janusz
J
Jazdzewski
Krystian
K
Wiechno
Wieslaw
W
Stachlewska
Elzbieta
E
Górnicka
Barbara
B
Bogdańska
Magdalena
M
Nauman
Janusz
J
Bartoszewicz
Zbigniew
Z
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006111:Graves Disease / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics*; D013961:Thyroid Gland / Q000201:enzymology*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D005732:Gangliosides; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human