THYROGLOBULIN, HUMAN

Description

Thyroglobulin is of special importance, because it serves as the matrix for the synthesis of T4 and T3 and as the storage form of the hormones and iodide. Thyroglobulin, a large glycoprotein with a molecular weight of 660,000 Da, accounts for about one-third of the weight of the thyroid gland. Thyroglobulin carries an average of 6 tyrosyl residues as monoiodo-L-tyrosine, 5 residues as diiodo-L-tyrosine, 0.3 residues as T3, and 1 residue as T4. From these values, it can be estimated that a 20 g thyroid stores roughly 10 μmol (7.8 mg) of T4 and 3 μmol (2.0 mg) of T3 and that the normal human thyroid gland contains enough potential T4 to maintain a euthyroid state for 2 months without new synthesis.
The synthesis of the thyroid hormones, T3 and T4, is regulated by thyrotropin (thyroid-stimulating hormone [TSH]), which stimulates the synthesis of thyroglobulin, thyroperoxidase (TPO), and hydrogen peroxide. The formation of the thyroid hormones depends on an exogenous supply of iodide. The thyroid gland is unique in that it is the only tissue of the body able to accumulate iodine in large quantities and incorporate it into hormones. Approximately 25% of the body's supply of iodide is located in the thyroid gland. The iodine atoms play a unique role in the conformational preferences for T3 and T4 because of their large steric bulkiness. The metabolism of iodine is so closely related to thyroid function that the two must be considered together. The formation of thyroid hormones involves the following complex sequence of events: 1) active uptake of iodide by the follicular cells, 2) oxidation of iodide and formation of iodotyrosyl residues of thyroglobulin, 3) formation of iodothyronines from iodotyrosines, 4) proteolysis of thyroglobulin and release of T4 and T3 into blood, and 5) conversion of T4 to T3.

Uses

Proloid (Parke-Davis).

Uses

Often used as a carrier protein for the production of antibodies. Its advantage is the large number of tyrosine residues that can be used for conjugation using the diazo reaction.

Biological Functions

Thyroid hormones regulate the turnover of carbohydrates, lipids, and proteins. They promote glucose absorption, hepatic and renal gluconeogenesis, hepatic glycogenolysis, and glucose utilization in muscle and adipose tissue. They increase de novo cholesterol synthesis but increase low-density lipoprotein degradation and cholesterol disposal even more, leading to a net decrease in total and in low-density lipoprotein cholesterol plasma levels. Thyroid hormones are anabolic when present at normal concentrations; they then stimulate the expression of many key enzymes of metabolism.

General Description

Thyroglobulin, a glycoprotein, is composed of several peptidechains; it also contains 0.5% to 1% iodine and 8% to10% carbohydrate in the form of two types of polysaccharide.The formation of thyroglobulin is regulated by TSH.Thyroglobulin has no hormonal properties. It must be hydrolyzedto release the hormonal iodothyronines thyroxineand liothyronine.

Biochem/physiol Actions

Thyroglobulin has been shown to induce expression of platelet activating factor in human peripheral blood mononuclear cells which is found elevated in some patients with thyroid disease.

Mechanism of action

The two most important actions of thyroid hormone are those related to oxygen consumption and those related to protein synthesis. Most effects of thyroid hormones can be related to the activation of genes following the binding of the hormone to high-affinity receptors of cell nuclei, but direct interactions of thyroid hormones with other cellular receptors cannot be excluded.