Thyroid binding proteins

Thyroid hormone is liberated into the bloodstream by the process of proteolysis within thyroid cells. T4 and T3 are transported in the bloodstream by three proteins thyroid-binding globulin, thyroid-binding prealbumin, and albumin. Only the unbound (free) thyroid hormone is able to diffuse into the cell, elicit a biologic effect, and regulate thyroid-stimulating hormone (TSH) secretion from the pituitary. 

The plasma half-life of T4 is approximately 7 days, and that of T3 is 1 to 1.5 days. These relatively long plasma half-lives result from binding of T3 and T4 to several transport proteins in the blood. Of these transport proteins, thyroid-binding globulin (TBG) has the highest affinity for these hormones and carries approximately 70% of... 

The lodothyronines secreted by the thyroid gland into thyroid vein blood are of limited solubility. They equilibrate rapidly, however, through noncovalent association with three major binding proteins thyroid binding globulin (TBG), transthyretin (TTR formerly called T4 binding prealbumin), and albumin. Thyroid... 

Thyroxine (3, 5, 3,5-L-teraiodothyronine, T4) is a thyroid hormone, which is transformed in peripheral tissues by the enzyme 5 -monodeiodinase to triiodothyronine. T4 is 3-8 times less active than triiodothyronine. T4 circulates in plasma bound to plasma proteins (T4-binding globulin, T4-binding prealbumin and albumin). It is effective in its free non-protein-bound form, which accounts for less than 1%. Its half-life is about 190 h. 

Hemopexin (binds heme) Retinol-binding protein (binds retinol) Sex hormone-binding globulin (binds testosterone, estradiol) Thyroid-binding globulin (binds T4, T3) Transferrin (transport iron)... 

Animal studies have shown that the immune system is sensitive to exposure. Mice fed diets containing 50 or 5 00 ppm technical-grade pentachlorophenol showed greatly reduced immunocompetence in the form of increased susceptibility to the growth of transplanted tumors. Oral and intraperitoneal administration to animals causes adverse effects on thyroid homeostasis and on the thyroid gland. Competition for serum protein thyroxine binding sites may account for the antithyroid effects of pentachlorophenol. ... 

Oral contraceptives have their most significant effect on endocrine parameters. Blood cortisol, thyroxine, protein-bound iodine, T3 uptake, and urinary free cortisol are elevated. Urinary 17,21-dihydroxy steroids, 17-ketosteroids, and estrogens are decreased. There is no effect on urinary catecholamines or VMA (Table 10) (LIO). The effect of thyroid functions tests is due to the administered hormone stimulating an increase in the production of thyroid-binding globulin which in turn binds 1-thyroxine. The lowering of free thyroxine stimulates the anterior pituitary to produce thyrotropin, which in turn stimulates the thyroid to produce more thyroxine. Since the additional thyroxine is bound to the extra protein, there is an equilibrium and the patient remains clinically euthyroid, but the protein-bound iodine and the thyroxine are elevated. 

A model of thyroid hormone action is depicted in Figure 38-4, which shows the free forms of thyroid hormones, T4 and T3, dissociated from thyroid-binding proteins, entering the cell by active transport. Within the cell, T4 is converted to T3 by 5 -deiodinase, and the T3 enters the nucleus, where T3 binds to a specific T3 receptor protein, a member of the c-erb oncogene family. (This family also includes the steroid hormone receptors and receptors for vitamins A and D.) The T3 receptor exists in two forms, a and B. Differing concentrations of receptor forms in different tissues may account for variations in T3 effect on different tissues. 

SchusslerGC. 2000. Tlie thyroxine-binding proteins. Thyroid 10 141-149. 

An absence of R-type binding protein has been reported in two adult siblings by Carmel and Herbert (C20). R-Type protein was virtually absent from their leukocytes and saliva, and as was expected they had very low levels of serum vitamin B12. The absence of the protein did not appear to have any adverse effects. Other members of this family have also been found to have an absence of, or very low levels of, R-protein (H26). There was no general deficiency of plasma glycoproteins in these patients and the amounts of thyroid binding globulin, thyroxine, ceruloplasmin, and transferrin were all normal. 

Several proteins, with binding activities for thyroid hormones, have been detected in a variety of cell types and with different subcellular localizations, i.e., in the plasma membrane, the sarcoplasmic reticulum, the cytosol, the mitochondria and... 

The concentration of free rather than bound thyroxine is considered to be the most accurate assessment of thyroid activity as this is the fraction which can penetrate cell membranes and exert a metabolic effect. Free thyroxine exists in equilibrium with thyroxine bound to globulin, albumin, and prealbumin. Any changes in the concentration of thyroid binding proteins leading to an increase in free hormone. Thyroid binding prealbumin is reduced after all kinds of stress and the reduction is significant within 24 hours. 

The binding capacity of thyroid-binding proteins is related directly to the concentration of the proteins in plasma. Thyroid-binding pre-... 

The importance of specific structural features in binding to the various thyroid binding proteins has been suggested from numerous studies measuring the relative binding affinities of the hormones and their analogues for these serum, nuclear and membrane proteins (30-36). These studies indicate that the binding site requirements are different for each of the proteins. 

Relative Binding Affinities and Biological Potencies of Selected Thyroid Hormones and Metabolites to Thyroid Binding Proteins... 

A. Wang R, Nelson JC, Weiss RM, Wilcox RB. Accuracy of free thyroxine measurements across natural ranges of thyroxine binding to serum proteins. Thyroid 2000 10 31-9. 

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