Thyroid Hormones Are Transported in the Plasma Attached to Plasma Proteins
As indicated in Chapter 33, lipid-soluble hormones are transported in the vascular system through association with specific binding plasma proteins. There is considerable species variation in the proteins that bind thyroid hormones.
The most important carrier protein is TBG, which has high affinity for T4, although it also has low capacity because of its low concentration. TBG also is an important carrier protein for T3. TBG has been reported in all domestic animals except the cat. Albumin is also involved in the transport of thyroid hormones; however, albumin has low affinity for T3 and T4 but high capacity because of its high concentration in plasma. In the absence of TBG, albumin is the most important carrier of thyroid hormones. All species have a third plasma protein, thyroxine-binding prealbumin, which is specific for T4 and has a specificity and capacity that are intermediate between those of TBG and albumin. The term prealbumin refers to the migration of the protein during electrophoresis, not to synthesis of the molecule.As with all lipid-soluble hormones that are transported in plasma, most of the T3 and T4 is bound; little is free to interact with receptors on the cells of the target tissues. The amount of thyroid hormone that is free in plasma is remarkably low (e.g., in humans, 0.03o∕o of T4 and 0.3% of T3). In dogs the amount of free hormone is somewhat greater (slightly less than 1.0% for T4 and slightly more than 1.0% for T3) because of less affinity between plasma-binding proteins and thyroid hormones in canine plasma than in human plasma. The equilibrium between free and bound hormone is easily shifted because of physiological or pharmacological situations, such as the increase in estrogen concentrations that occurs during pregnancy. Estrogens cause increased synthesis of TBG by the liver, resulting in a shift toward the bound form. Adjustments to maintain a normal amount of free hormone occur rapidly, with a decline in the rate of metabolism or with stimulation of thyroid hormone production through the release of thyroid- stimulating hormone (TSH).