Thyroid hormones synthesis/transport

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.

FIGURE 73-2. Thyroid hormone synthesis. Iodide is transported from the plasma, through the cell, to the apical membrane where it is organified and coupled to the thyroglobulin (TG) synthesized within the thyroid cell. Hormone stored as colloid re-enters the cell through endocytosis and moves back toward the basal membrane, where T4 is secreted. 

Thyroid hormone synthesis takes place at the follicular cell level through a number of different steps (Figure 56.1). The active transport of iodide into the follicular cells is... 

Figure 101.2 Thyroid iodide transport and organification. A schematic of a thyroid follicular cell showing the key aspects of thyroid iodine transport and thyroid hormone synthesis. TSHR, TSH receptor NIS, sodium iodide symporter TPO, thyroid peroxidase Tg, thyroglobulin.

Reduced synthesis of proteins in the liver can also affect the end omnium. Thyroxine-binding globulin (TBG), the major thyroid hormone transport protein, has been found to be transiently but marisedly decreased during I-ASP therapy [129,130]. In extended observations Ferster et al. [131] demonstrated a decrease of total T4, FT4, total T3, and TBG during induction therapy. The changes in T4... 

Lipid-soluble hormones act usually by gene activation/deactivation. Examples of these hormones include steroids, thyroid hormone, and vitamin A (retinoic acid). The hormones are transported through the circulation in association with a hormone-binding protein and are soluble in the plasma membrane of the cell. Their receptors are intracellular, and they act on gene transcription (the synthesis of messenger RNA) rather than at the protein level. Thus, they act more slowly than do the soluble hormones, on the scale of days rather than minutes. 

The concentration of thyroid hormones in a given responsive cell depends on a number of factors (Fig. 2) including 1) the production of the two major hormones in the thyroid gland and their secretion in the blood (see Ref. 6) (both the synthesis and the secretion processess are themselves regulated by TSH) 2) the transport of T4 and T3 in the blood and then their degradation in the liver and in the kidney 3) the uptake of thyroid hormones by the different target cells 4) the peripheral conversion of the prohormone, T4, to the active (T3) and the inactive ( reverse T3 or r-T3) derivatives in the responsive cells. 

Thyroid hormones stimulate protein synthesis in most cells of the body. They also stimulate oxygen consumption by increasing the levels of the Na% K+-ATPase ion transporter. The generation of plasma membrane Na+ and K+gradients by the Na+, K+-ATPase is a major consnmer of cellular adenosine triphosphate (ATP), leading to stimulation of ATP synthesis in the mitochondria... 

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