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Chapter 4: Thyroid Gland

OBJECTIVES

OBJECTIVES

  • Identify the steps and control factors of thyroid hormone biosynthesis, storage, and release.

  • Describe the role of iodine in thyroid hormone synthesis.

  • Explain the importance of thyroid hormone binding in blood in maintaining free and total thyroid hormone levels.

  • Understand the significance of deiodination of tetraiodothyronine (T4) to triiodothyronine (T3) and reverse T3 (rT3) in extrathyroidal tissues.

  • Understand how thyroid hormones produce their cellular effects.

  • Describe the physiological effects of T4 and T3 on development and metabolism.

  • Understand the causes and consequences of excess and deficiency of thyroid hormones.

Thyroid hormones play important roles in maintaining energy homeostasis and regulating energy expenditure. Their physiologic effects, mediated at multiple target organs, are primarily to stimulate cell metabolism and activity. The vital roles of these hormones, particularly in development, differentiation, and maturation, are underscored by the severe mental retardation observed in infants with deficient thyroid hormone function during gestation. Thyroid hormones are derived from the amino acid tyrosine and are produced by the thyroid gland in response to stimulation by thyroid-stimulating hormone (TSH) produced by the anterior pituitary. TSH, in turn, is regulated by the hypophysiotropic peptide thyrotropin-releasing hormone (TRH) (Figure 4–1). Thyroid hormone production is also under regulation by dietary iodine.

Figure 4–1

The hypothalamic-pituitary-thyroid axis. Thyrotropin releasing hormone (TRH) is synthesized in parvicellular neurons of the paraventricular nucleus of the hypothalamus and released from nerve terminals in the median eminence from where it is transported via the portal capillary plexus to the anterior pituitary. TRH binds to a G-protein–coupled receptor in the anterior pituitary leading to an increase in intracellular Ca++ concentration, resulting in stimulation of exocytosis and release of thyroid-stimulating hormone (TSH) into the systemic circulation. TSH stimulates thyroid gland to increase the synthesis and secretion of thyroxine (T4) and triiodothyronine (T3) into the circulation. T4 and T3 inhibit the secretion of thyrotropin (TSH) both directly and indirectly, by inhibiting the secretion of TRH. Additional factors that inhibit TSH release are glucocorticoids, somatostatin, and dopamine. Iodide is transported into the cytosol of the follicular cell by a sodium-iodide symporter. Two Na+ ions are transported inside the thyroid follicular cell with each iodide molecule. Na+ moves down its concentration gradient, which is maintained by a Na/K ATPase that constantly pumps Na+ out of the cytoplasm of the thyroid follicular epithelial cell maintaining the low intracytoplasmic Na+ concentrations. Iodide must reach the colloid space, where it is used for organification of thyroglobulin. This process is achieved by efflux through the iodide channel. One of the early effects of TSH binding to its receptor is the opening of these channels facilitating the leak of iodide into the extracellular space. This transcellular transport of iodide relies on the functional and morphological polarization of the thyroid follicular epithelial cell.

An illustration shows the hypothalamic-pituitary-thyroid axis. The TRH in the hypothalamus stimulates GPCR (aq) thyrotrophin in the anterior pituitary that produces TSH which stimulates GPCR (gas) follicular epithelial cells in the thyroid gland that produces T3 and T4 that results in target tissue effects. T3 and T4 lead back to the anterior pituitary and induces DA, SS, and Cortisol in the hypothalamus. A micrograph shows the cells in the thyroid gland. The parts labeled are fibroblast, follicular epithelial cell, blood capillary, colloid, thyroid follicle (secretory unit), lymphocyte, parafollicular cell (C cell), and adipocyte. The enhanced view of the follicular epithelial cell shows an I-channel at the bottom and 3 Na plus ion or I negative ion symporter and 3 Na plus ion or 2 K plus ion ATPase at the top. The outer layer is labeled as an apical membrane. The cell has low Na plus ions.
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