Triiodothyronine transport

S aij a A, Princi P, D Amico N, De Pasquale R, Costa G. Effect of Vaccinium myrtillus anthocyanins on triiodothyronine transport into brain in the rat. Pharmacol Rev 1990 22 59-60. 

T. Terasaki and W.M. Pardridge, Stereospecificity of triiodothyronine transport into brain, liver and salivary gland role of carrier- and plasma-protein mediated transport. Endocrinology 121 1185-1191 (1987). 

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

Amine hormones include the thyroid hormones and the catecholamines. The thyroid hormones tend to be biologically similar to the steroid hormones. They are mainly insoluble in the blood and are transported predominantly (>99%) bound to proteins. As such, these hormones have longer half-lives (triiodothyronine, t3, = 24 h thyroxine, T4, = 7 days). Furthermore, thyroid hormones cross cell membranes to bind with intracellular receptors and may be administered orally (e.g., synthryoid). In contrast to steroid hormones, however, thyroid hormones have the unique property of being stored extra-cellularly in the thyroid gland as part of the thyroglobulin molecule. 

Transport. A wellknown transport protein is hemoglobin in the erythrocytes (bottom left). It is responsible for the transport of oxygen and carbon dioxide between the lungs and tissues (see p.282). The blood plasma also contains many other proteins with transport functions. Prealbumin (transthyretin middle), for example, transports the thyroid hormones thyroxin and triiodothyronine. Ion channels and other integral membrane proteins (see p.220) facilitate the transport of ions and metabolites across biological membranes. 

Transport of thyroxin and triiodothyronin Maintenance of osmotic pressure transport of fatty acids, bilirubin, bile acids, steroid hormones, pharmaceuticals and inorganic ions. 

Thyroxine and triiodothyronine have many effects, a major one in mammals and birds being stimulation of energy metabolism in tissues. It has long been recognized that a deficiency of thyroid hormone is reflected in an overall lower basal metabolic rate (Chapter 6). Maley and Lardy observed that thyroxine uncouples oxidative phosphorylation (Chapter 18) in isolated mitochondria.117 When mitochondria from animals receiving extra thyroxine were compared with those from control animals, an increased rate of electron transport was observed. However, there was little or no change in the P / O ratio. Thus, the hormone apparently increased the rate of electron transport... 

Thyroid cells actively transport iodine (I-), which is incorporated into a few tyrosine residues of thyroglobulin by the enzyme iodoperoxidase. After condensation of iodinated tyrosine residues, the thyroglobulin is proteolytically degraded liberating thyroxine and triiodothyronine. 

Fleck C, Bachner B, Gockeritz S, et al. Ex vivo stimulation of renal tubular PAH transport by dexamethasone and triiodothyronine in human renal cell carcinoma. Urol Res 2000 28 383-390. 

Bilberry extract 200 mg/(kg day) administered intraperitoneally to euthyroid rats increased radiolabeled triiodothyronine (T3) transport into the brain, compared to vehicle only (21). Postulated mechanisms include central or peripheral inhibition of L-thyroxine s (T4) deiodination to T3 inhibition of T3 protein binding or enhanced T3 binding to carrier proteins in the brain capillary wall (21). Whether bilberry could interact with thyroid replacement therapy remains to be seen. 

Transthyretin (prealbumin) and retinol-binding protein (RBP) are transport proteins that migrate together as a 1 1 molecular complex. Transthyretin was originally named prealbumin because of its electrophoretic mobility it was renamed in 1981 to reflect its binding and transport of both thyroid hormones (thyroxine and triiodothyronine) and RBP. 

Blondeau, J. P., Beslin, A., Chantoux, F., and Francon, J., Triiodothyronine is a high-affinity inhibitor of amino acid transport system LI in cultured astrocytes, /. Neurochem., 60, 1407, 1993. 

The expression of the sodium iodide symporter is perhaps nowhere more important than in the thyroid gland. A complete review of the physiological importance of the thyroid is beyond the scope of this chapter. It is sufficient to say that the symporter provides the iodine needed for normal thyroid function. Once the symporter has been trafficked to the basolateral surface of the thyrocyte, it can transport iodine from the blood into the cell. Once inside the cells, iodine is transported to the apical membrane where it is organified through attachment to a tyrosine residue and incorporated into the thyroid hormone thyroglobulin. The thyroglobu-lin is then stored inside thyroid follicles as colloid, to be released into the bloodstream as thyroid hormones (thyroxine and triiodothyronine) via TSH stimulation. 

The function of the thyroid gland is to take iodine, found in many foods, and convert it into thyroid hormones thyroxine (TJ and triiodothyronine (T3). Thyroid cells are the only cells in the body which can absorb iodine. These cells combine iodine and the amino acid tyrosine to make T3 and T4. T3 and T4 are then released into the blood stream and are transported throughout the body, where they control metabolism (conversion of oxygen and calories to energy). Every cell in the body depends on thyroid hormones for regulation of their metabolism. The normal thyroid gland produces about 80% T4 and about 20% T3, however, T3 possesses about four times the hormone strength of T4. 

---