Unique Pattern of N-Glycosylation, Sialylation, and Sulfonation on TSH Molecules in Serum of Children up to 18 Months

Abstract

Context: N-glycosylation and glycan composition of human TSH molecules modulate the biological properties of TSH in different physiological and clinical situations. The degree of sialylation of serum TSH was reported to be very low in normal third-trimester fetuses compared with normal adults. The circulating TSH glycoforms and their glycan compositions in young children have hitherto not been determined. Objective: To characterize N-glycosylation and glycan composition of circulating TSH molecules in young children. Design, Participants, Main Outcome Measures: Serum samples were obtained from euthyroid individuals: 33 children, age 2 weeks to 3 years, and 264 adults. The di-glycosylated TSH and tri-glycosylated TSH glycoforms were determined and characterized with respect to sialylation and sulfonation. The TSH N-glycosylation was also examined in pituitary extracts of 75 individuals. Results: In children up to 18 months of age, most TSH molecules were low-N-glycosylated, high-sulfonated, and low-sialylated compared with older children and adults. The degree of N-glycosylation was similar in serum and pituitary extracts up to 3 months of age and after that was higher in serum than in pituitary extracts. Conclusions: Children up to age 18 months had low-sialylated TSH molecules, similar to those reported for third-trimester fetuses. Most TSH molecules in young children were of smaller size and less negatively charged, favoring transport into their target tissues. The low sialylation favors a high biopotency at thyroid and extrathyroidal TSH receptors. A delayed development of the liver SO3-N-acetylgalactosamine receptor function after birth is a likely explanation of the highly sulfonated TSH molecules in serum samples of infants.