Transport and Metabolism of Thyroid Hormones

Mutations in a human serum albumin gene that substitute either histidine or proline for arginine at position 218 increase binding affinity for T4. These mutations are autosomal dominant and occur with relatively high frequency. Carriers of these mutations have high levels of total serum T4 but their free-T4 and TSH concentrations are within the normal range. Individuals are euthyroid (normal thyroid) and their conditions are known as familial dysalbumine-mic hyperthyroxinemia (FDH). 

Reaction catalyzed 5-deiodination (outer ring) 5-deiodination (outer ring) 5-deiodination (inner ring) 

Tissue distribution Liver, kidney, thyroid, et al. Brain, pituitary, skin, brown fat Liver, kidney, et al. 

both involving the removal of the inner ring 5-iodide. The type III enzyme is widely distributed among tissues and is responsible for the formation of almost all (95%) of the circulating rT3. Its activity is not altered by most of the factors or conditions that inhibit the activity of types I or II deiodinases, and this explains why there is a reciprocal relationship between the plasma levels of T3 and rT3. 

Inorganic iodide liberated from deiodinations enter the extracellular compartment and is excreted in the urine ( 488 fig/d) or stool ( 12 /u,g/d via bile), or is reabsorbed by the thyroid gland ( 108 /rg/d) for resynthesis of thyroid hormones. At the average daily intake of 500 /zg inorganic iodide, this amounts to no net change in the iodide status, although the small amount of iodide that 

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Thyroid hormone activity is determined predominantly by intracellular concentrations of (free) T3 in the tissues. This T3 bioavailability depends on 1) the secretion of T4 and T3 by the thyroid, 2) the conversion of T4 to T3 outside the thyroid, 3) the metabolic clearance of T3 and 4) exchange of T4 and T3 between plasma and tissues. It is the purpose of this chapter to review recent advancements in the study of the transport and metabolism of thyroid hormone. Especially the role of deiodination, conjugation and tissue uptake mechanisms will be emphasized in the regulation of thyroid hormone action. 

In the human, TTR is one of three plasma proteins involved in the transport of the thyroid hormones in blood (Ingbar, 1963 Oppenheimer, 1968). The principal transport protein for thyroid hormones in human plasma is thyroxine-binding globulin, and TTR plays only a lesser role in the normal transport and metabolism of thyroid hormones in man (Woeber and Ingbar, 1968). In the rat, however, TTR appears to be the major thyroid hormone transport protein (Davis et al., 1970 Sutherland and Brandon, 1976). 

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