Thyroid Gland

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* The thyroid gland is located immediately below the larynx on each side of and anterior to the trachea.

* The colloid contains thyroglobulin which contains the thyroid hormones. * The parafollicular cells contain calcitonin.

Iodide Kinetics
Average daily intake: 0.1 mg
Absorption: iodine to inorganic iodide in stomach and upper SI Transport & Metabolism: iodide (ECF) pool thyroid pool

hormone (T3T4 pool)
tissues (liver,muscle,etc)
thyroid-serum iodide ratio: 25 to 1
Clearance: kidneys

Synthesis & Release – stimulated by TSH

* The iodide in the ECF will enter the follicular cells (idodide trapping) through active transport (Sodium-Iodide Symport). * The iodide will then diffuse to the apical cells where it will be oxidized (catalyzed by thyroid peroxidase) to iodine to make it capable of binding directly with thyroglobulin. * Electron acceptor: hydrogen peroxide

* Iodine will enter the colloid through the Iodide-Chloride symport. * Within the colloid, tyrosine, which is contained in the thyroglobulin will be iodinated which will result in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT).

* MIT and DIT will undergo coupling reaction resulting in the formation of T3 and T4.

* When the thyroid cells are stimulated, iodinated thyroglobulin is taken back in to the follicular cells by endocytosis. * Lysosomal enzymes then digest thyroglobulin, releasing T3 and T4 into the circulation. * Leftover MIT and DIT are deiodinated by thyroid deiodinase. The iodine released is reutilized to synthesize more thyroid hormones.

The most important regulator of the thyroid gland function and growth is the hypothalamic-pituitary thyroid releasing hormone-thyroid stimulating hormone axis. Thyrotropin releasing hormone (TRH) secreted by the hypothalamus stimulates the anterior pituitary to secrete thyroid stimulating hormone. TSH regulates the secretion of T4 and T3 of the thyroid gland; it has immediate, intermediate, and long-term actions on the thyroid epithelium IMMEDIATE:

* Induction of pseudopod extension, endocytosis of colloid, formation of colloid droplets in the cytoplasm. * TSH also stimulates entry of glucose into the hexose monophostphate shunt pathway, which generates NADPH that is needed for the peroxidas reaction. * Stimulates proteolysis of thyroglobulin and release of T4 and T3 INTERMEDIATE:

* Occur after a delay of hours to days and involve protein synthesis and expression of numerous genes, including those encoding NIS, thyroglobulin, TPO, and megalin.

* Sustained TSH stimulation leads to hypertrophy and hyperplasia of follicular cells.

*Regulation is under exquisite negative-feedback control:
* Circulating TH act on the pituitary gland to decrease TSH secretion, primarily by repressing TSH β subunit gene expression. The pituitary gland expresses the high affinity type 2 deiodinase. Thus, small changes in free T4 in blood result in significant changes in intracellular T3. * Because the diurnal variation of TSH secretion is small, TH secretion and plasma concentrations are relatively constant. Only small nocturnal increases in secretion of TSH and release of T4 occur. * TH also feed back on hypothalamic TRH-secreting neurons. T3 inhibits the expression of the prepro-TRH gene. * Iodide is also an important regulator. At low levels, rate of TH synthesis is directly related to the availability of the iodide. * Circulating T4 and T3 act on the pituitary gland to decrease TSH secretion; if the levels of T4 and T3 fall, TSH secretion increases. It is free T4 and T3, not the protein-bound portions that regulate pituitary TSH output. The pituitary gland is capable of deiodinating T4 to T3, and the latter acts as the final effector molecule in...
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