Thyroid Binding

Thyroid Hormones Are Transported by Thyroid-Binding Globulin... 

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

C17. Chopra, I. J., Chua Tec, G. N., Mead, J. F., Huang, T. S., Beredo, A., and Solomon, D. H., Relationship between serum free fatty acid and thyroid binding inhibitor in nonthyroidal illness. J. Clin. Endocrinol. Metab. 60,980-984 (1985). 

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. 

In thyrotoxic Graves disease, there is an increase in the overall hormone production rate with a disproportionate increase in T3 relative to T4 (Table 20-1). Saturation of thyroid-binding globulin is increased due to the elevated levels of serum T4 and T3, which is reflected in an elevated T3 resin uptake. As a result, the concentrations of free T4, free T3, and the free T4 and T3 indices are increased to an even greater extent than are the measured serum total T4 and T3 concentrations. The TSH level is undetectable due to negative feedback by elevated levels of thyroid hormone at the pituitary. In... 

TBG, thyroid-binding globulin TSH, thyroid-stimulating hormone T3, triiodothyronine Lp thyroxine. 

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. 

Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. 

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. 

Cheek AO, Kow K, Chen J, McLachlan JA (1999) Potential mechanisms of action of thyroid disruption in humans Interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin. Environ Health Perspect, 107(4) ... 

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. 

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-... 

H4. Harvey, R. F., Semm thyroxine and thyroid binding globulin in seriously ill patients. Lancet i, 208-212 (1971). 

Through competitive binding to thyroid-binding globulin, salicylates in high concentrations can displace thyroxine and triiodothyronine, thus interfering with the results of diagnostic thyroid function tests (118). 

The health effect of endocrine disruptors is further complicated by the fact that an endocrine disrupter or a family of endocrine disruptors may have multiple mechanisms of actions. For example, PCBs may mimic estrogen, prevent binding of thyroid hormone to thyroid binding globulin, and accelerate the metabolism and excretion of several steroid hormones. 

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