TSH binding proteins in rat and human serum.
When serum of hypothyroid rats was fractionated on a Sephadex G-100 column, most of the immunoreactive TSH was found as a front running peak, together with the high molecular weight serum proteins. Similarly, a rTSH preparation (10 mU), chromatographed in the presence of 1 ml of normal rat serum also migrated at the front, however, when a high load of TSH (4.4 U) was added to 1 ml of serum, two immunoreactive peaks were found, suggesting the saturation of the front running fraction. Immunoelectrophoresis and autoradiography of rat or human sera containing the respective 125I-labelled TSHs showed binding of the labelled TSH to IgG, alpha-2-macroglobulin, and to a third unidentified protein, migrating near the albumin line. In order to determine if the bound TSH is biologically active, the high molecular weight protein fraction was separated from hypothyroid rat serum by 45% ammonium sulphate precipitation. Immunoreactivity was determined by RIA and the biological activity was determined, in vitro, by the stimulation of 99Tc uptake by FRTL-5 cells. The 45% ammonium sulphate precipitate contained almost all of the immunoreactivity and the bioactivity of the TSH of whole serum. These results indicate that: a) The endogenous circulating TSH in the hypothyroid rat exists mainly in a protein-bound form and this protein-bound TSH contains most of the hormonal bioactivity of the serum. b) Exogenous TSH binds to serum proteins in euthyroid and hypothyroid rats and in humans. There are three protein fractions in these sera that bind TSH, one of which is an immunoglobulin. The occurrence of TSH binding immunoglobulins may involve autoimmune mechanisms.
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001681:Biological Assay; D011232:Chemical Precipitation; D002850:Chromatography, Gel; D007037:Hypothyroidism / Q000276:immunology / Q000378:metabolism; D007122:Immunoelectrophoresis; D007074:Immunoglobulin G / Q000378:metabolism; D018828:Immunoglobulins, Thyroid-Stimulating; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood*
D001323:Autoantibodies; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; D013972:Thyrotropin