Intravenous thyrotropin (TSH)-releasing hormone releases human TSH that is structurally different from basal TSH.

To determine whether basal TSH differed structurally from TRH-released TSH, the TSH obtained from 11 normal subjects before and after the iv administration of TRH was characterized using lectin-affinity chromatography. TSH was applied to the following lectins: lentil, ricin (both before and after TSH treatment with neuraminidase), Concanavalin-A, wheat germ, Glycine max, Helix pomatia, Dolichos biflorus, Arachis hypogaea, and Vicia villosa (isolectin B4). After each column was washed to elute unbound TSH, the bound TSH was eluted using the appropriate specific sugar, and TSH in the column fractions was measured by immunoradiometric assay. Basal TSH was found to have a different oligosaccharide composition than TSH in serum 30 min after TRH administration. The basal TSH had fewer core fucose residues and more exposed galactose residues than the TSH released after TRH treatment. The amounts of oligosaccharide branching and the amounts of N-acetylglucosamine were similar, and the degrees of sialylation for both basal TSH and TRH-released TSH were highly variable. No exposed N-acetylgalactosamine residues were detected in either type of TSH; if present, these residues may have been uniformly sulfated. The biochemical differences detected in basal TSH vs. TRH-released TSH may reflect different post-translational processing and storage of these molecules in thyrotrophs. These data provide an example of the release of particular isoforms of human TSH depending on a hypothalamic factor, a general principle that may be important in the physiological control of thyroid function by the pituitary.