The thyroid gland is the source of tetraiodothyronine T4 and triiodothyronine (T3). The basic unit of the thyroid gland is the follicle which consists of a single layer of epithelial cells surrounding a centrial lumen that contains colloid or stored hormone.
T4 and T3 are synthesized from tyrosine and iodide by the enzyme peroxidase. Tyrosine is incorporated in peptide linkage within the protein thyroglobulin. After iodination, two iodotyrosine molecules are coupled to yield iodothyronines.
Secretion of stored T4 & T3 requires retrieval of thyroglobulin from the follicle lumen by endocytosis. To support hormone synthesis, Iodine is actively concentrated by the gland and conserved within it by recycling the iodotyrosine molecules that escape coupling within the thyroglobulin.
Thyrotropin (TSH) acts on the thyroid gland via its plasma membrane receptor and cAMP to stimulate all steps in the production of T4 & T3. These steps include iodide uptake, iodination and coupling, and retrieval from thyroglobulin. TSH also stimulates glucose oxidation, protein synthesis, and growth of the thyroid epithelial cells. This last effect is partly mediated by insulin-like Growth factors.
More than 99.5% of the T4 and T3 circulate bound to the protein thyroglobulin (TBG), transthyretin, and albumin. Only the free fraction of T4 & T3 are biologically active. Changes in in TBG levels require corresponding changes in in thyroid hormone secretion to maintain normal concentrations of free T4 & T3.
T4 functions largely as a prohormone. Monodeiodination of the outer ring yields 75% of the daily production of T3, which is the principle active hormone. Alternatively, monodeiodination of the inner ring yields reverse T3 (rT3), which is biologically inactive. Proportioning of T4 between T3 & rT3 regulates the availability of active hormone.
T3 and, to a much lesser extent, T4 bind to a thyroid hormone receptor (TR) that itself exists linked to thyroid regulatory elements (TREs) in target DNA molecules. Activation results in expression or suppression of the expression of a large number of enzymes. As well as structural and other functional proteins.
Thyroid hormone increases and is a major regulator of basal metabolic the rate. Oxygen utilization is increased by a mechanisms that include increases in in the size and number of mitochondria, Na,K-ATPase activity, and the rates of glucose and fatty acid oxidation and synthesis
Additional important actions of thyroid hormone are to increase heart rate, cardiac output, and ventilation and to decrease peripheral resistance. These actions require the the increased tissue oxygen demand. The corresponding increase in heat production leads to increased sweating. Substrate mobilization and disposal of metabolic products are enhanced.
Other thyroid hormone effects on the central central nervous system and skeleton are crucial for normal growth and development. With children. in the absence the hormone, brain development is retarded and cretinism results. The stature shortens and the bones fail to mature. With adults, thyroid hormone increases the rate of bone resorption and the rates of skin and hair degradation.
Hyperthyroidism and hypothyroidism are usually easily diagnosed. Both are very amenable to therapy.