Observations Concerning the Binding of Thyroid Hormones by Human Serum Prealbumin*

Abstract

There is general agreement that thyroxine (T4)1 is the major component of the thyroid hormone in blood, where it exists almost entirely in a dissociable complex with certain plasma proteins. From the numerous studies that followed the discovery of the TU-binding (a)-globulin of plasma (TBG) in 1952, it first appeared that the binding of T. in plasma could be mainly ascribed to binding sites of high avidity but low concentration, contributed by TBG. A secondary role was ascribed to binding sites of low avidity but almost unlimited concentration, contributed by albumin. These conclusions, based almost entirely on data obtained by electrophoretic separation of serum or plasma proteins on filter paper in barbital buffer at pH 8.6, have been considered in several recent reviews (1, 2).In 1956, during efforts to purify TBG, an additional T4-binding protein was observed in subfractions of human plasma proteins. Subsequent experiments revealed that a T4-binding protein of similar electrophoretic mobility could be consistently demonstrated in unfractionated normal human serum when electrophoretic separations were performed in a buffer containing tris (hydroxymethyl)aminomethane (Tris) and maleic acid, rather than barbital. Because of its rapid anodal migration at pH 8.6, this protein was termed the thyroxine-binding prealbumin (TBPA) (3). It avidly bound T4, but failed to bind significant quantities of 3,5,3'-triiodothyronine (T3).

Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects

“…This pattern of binding is that which is characteristic of the deaminated derivatives of T4 and T3 (18,19). Similar studies were carried out with pooled, twice chromatographed T3 from sera of G. T. and J. M. In this instance, the radioactive material from the subjects' sera was bound by TBG and albumin, but not by TBPA, as is compatible with the behavior of T3 (18,19).…”

Study of Four New Kindreds with Inherited Thyroxine-Binding Globulin Abnormalities POSSIBLE MUTATIONS OF A SINGLE GENE LOCUS

“…Similarly, the BMR (5,7,8,20,39), cholesterol (3,5,7,13,16,17,20,39,50,55,56), and thyroidal 'I uptake (3, 7, 10, 15-17, 20, 39, 50, 55-57) were within normal limits. No evidence for thyroid autoimmunity could be obtained from measurement of circulation thyroglobulin antibodies (5,11).…”

“…The remaining 5% of the total 'I activity was lost in the buffer tank and probably represents iodide-'I contaminant. Since in the presence of barbital buffer, T4 does not bind to TBPA (39), no T4-l5I was recovered from the prealbumin zone. The specific activity of TBG, in the pooled two peak fractions, increased 17-fold and the recovery was 75%.…”

Salicylate-induced increases in free triiodothyronine in human serum

“…This interference was first demonstrated in human serum by Osorio in 1962 (22). In these studies, paper electrophoresis was used but subsequent studies using this technique have emphasized only the salicylate effect on TBPA-T4 binding (7).…”

“…Previous studies have shown that salicylate and its congeners decrease the binding of To to the binding proteins in human serum (5)(6)(7). These drugs were found to interfere specifically with the binding of To to thyroxine-binding prealbumin (TBPA).…”