Thyroid hormone synthesis and secretion. (See text for details.) DIT, diiodotyrosine; MIT, monoiodotyrosine.
licular cells, migrate toward the apical region of the stimulated cells. The lysosomes fuse with the colloid droplets and hydrolyze the thyroglobulin to its constituent amino acids. As a result, T4 and T3 and the other iodinated amino acids are released into the cytosol.
Secretion of Free T4 and T3. T4 and T3 formed from the hydrolysis of thyroglobulin are released from the follicular cell and enter the nearby capillary circulation, however, the mechanism of transport of T4 and T3 across the basal plasma membrane has not been defined. The DIT and MIT generated by the hydrolysis of thyroglobulin are deiodi-nated in the follicular cell. The released iodide is then re-utilized by the follicular cell for the iodination of thy-roglobulin (see Fig. 33.3).
Binding of T4 and T3 to Plasma Proteins. Most of the T4 and T3 molecules that enter the bloodstream become bound to plasma proteins. About 70% of the T4 and 80% of the T3 are noncovalently bound to thyroxine-binding globulin (TBG), a 54-kDa glycoprotein that is synthesized and secreted by the liver. Each molecule of TBG has a single binding site for a thyroid hormone molecule. The remaining T4 and T3 in the blood are bound to transthyretin or to albumin. Less than 1% of the T4 and T3 in blood is in the free form, and it is in equilibrium with the large protein-bound fraction. It is this small amount of free thyroid hormone that interacts with target cells.
The protein-bound form of T4 and T3 represents a large reservoir of preformed hormone that can replenish the small amount of circulating free hormone as it is cleared from the blood. This reservoir provides the body with a buffer against drastic changes in circulating thyroid hormone levels as a result of sudden changes in the rate of T4 and T3 secretion. The protein-bound T4 and T3 molecules are also protected from metabolic inactivation and excretion in the urine. As a result of these factors, the thyroid hormones have long half-lives in the bloodstream. The half-life of T4 is about 7 days,- the half-life of T3 is about 1 day.
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