Key Words

Follicle cell-these cells surround the colloid containing lumen of the thyroid follicle.
These cells are cuboidal when they are inactive. When they are active they elongate and become columnar in shape. They are stimulated by Thyroid Stimulating Hormone (TSH). These cells play a role in the production of T₃ and T₄.
*See Handout from 8/19 for figures and additional info.

Iodide- from diet is transferred across the basement membrane of the follicle cell (from the blood to the cytosol) and becomes oxidized (from 2I- to I2). This reaction is catalyzed by Thyroid Peroxidase (TPO). Tyrosine molecules of the thyroglobulin protein are iodized on the tyrosine amino acids to produce monoiodotyrosine(MIT) and diiodotyrosine(DIT). This reaction is also catalyzed by TPO. MIT=T1, DIT=T2 These molecules are coupled with each other to produce T₃ and T₄. MIT+DIT--->T₃ and DIT+DIT--->T₄ Iodide is later removed from these hormones (by deiodizing enzymes) and recycled.

Thyroglobulin- high molecular weight glycoprotein containing ~ 100 tyrosine which can become iodized. They are produced by the Rough Endoplasmic Reticulum and modified in the Golgi Apparatus. They are packaged into small vesicles and sent to the lumen of the thyroid by exocytosis.

MIT- monoiodotyrosine/T1 This is created when tyrosine is iodized once(TPO). This will couple with DIT to become T₃.

DIT- diiodotyrosine/T2 This is created when tyrosine is iodized twice (TPO). Can couple with MIT to become T₃ or more commonly it can couple with another DIT to become T₄.

T₃- triiodothyronine, thyroid hormone which contains 3 iodide atoms. It is made from MIT + DIT, or by T₄ cleaved by 5’monodeiodinase. It is the ACTIVE thyroid hormone. T₃ is more biologically active and has a higher affinity for its receptor protein at the sight of action. * see funcns below

T₄- thyroxine, thyroid hormone which contains 4 iodide atoms. It is made from two DITs. Can be cleaved by 5’monodeiodinase to become T₃ which is more potent. T₄ is created in a much larger quantity than T₃. It is moved from the thyroid and has a longer 1/2 life than T3 (7 days vs. 1.3 days), has a very high affinity for TBG * see functions below

*(T₃ and T₄) Thyroid hormones have 3 major functions: Regulate O2 use and Basal Metabolic Rate, Regulate Cellular Metabolism, and Regulate Growth and Development

Thyroxine Binding Globulin (TBG)- binding protein which binds to T₃ and T₄ in blood. TBG+T₃ have a half life of 1.3days, TBG+T₄ have a half life of 7 days. Due to the high affinity for TBG, T₃ and T₄ are released into tissue cells slowly. Once they are inside they bind to intracellular proteins.

TRH:  

TSH:  

Thyroid-stimulating antibodies:  

Graves' Disease:  

Hashimoto's Thyroiditis:  

Goiter:  

Total vs. Free thyroid hormone measurement:  

Objectives

Synthesis:

1. Iodide Trapping-Iodide (I-) is actively transported across the basement membrane of the follicle cell and trapped.
2. Oxidation of Iodide- I- + I- -->I2 (oxidation by TPO)
3. Synthesis of TBG- thyroglobulin glycoprotein is made and extruded into lumen of follicle
4. Iodination of Tyrosine-Tyrosines bind I2 to become MIT, DIT (TPO)
5. Coupling of T₁ and T₂ (or MIT and DIT)- within Thyroglobulin these molecules couple to produce T₃ (MIT+DIT) and T₄(DIT+DIT) This step is also catalyzed by TPO.
6. Pinocytosis and Digestion of Colloid- Thyroglobulin reenters the cell by endocytosis and is hydrolyzed
7. Deiodination of MIT, DIT to reuse Iodide
8. Transport of T₃, T₄ through blood to target tissues. T3 and T4 are bound to TBG when they are in blood.

Storage:

• T₃ and T₄ are stored as part of Thyroglobulin molecule in the colloid. When needed they are secreted into the blood and bind TBG. They have half lives of 1.3 days and 7 days respectively.

Compartmentalization:

• Blood carries I- which crosses into the cell and gets trapped.
• I- is sent into colloid and TPO acts on it producing I2.
• Thyroglobulin is made in RER-->Golgi-->colloid in vesicles
• In colloid I2 binds to Thyroglobulin to make and store Thyroid hormones
• When they are ready to be secreted, they endocytose into the cell. Thyroglobulin is detached and reused. This is done in the lysosomes within the follicle cell. T₃ and T₄ are released into the blood and bind to TBG.