Thyroid Hormone Synthesis Overview

Aug 10, 2024

Synthesis and Secretion of Thyroid Hormones

Overview

  • Discussion of the synthesis and secretion processes of thyroid hormones.
  • Reference to a diagram from Guyton for clarity.

Diagram Explanation

  • Follicular Epithelial Cells: Line the follicles of the thyroid glands.
    • Apical Membrane: Faces the follicular lumen.
    • Basolateral Membrane: Closely associated with blood vessels.

Steps in Thyroid Hormone Synthesis

1. Iodide Trapping

  • Transport Mechanism:
    • Sodium Iodide Symporter: Active transport mechanism that brings iodide into the epithelial cell.
    • Requires energy from Sodium-Potassium ATPase Pump (pumps 3 sodium out and 2 potassium in, creating a sodium gradient).

2. Synthesis of Thyroglobulin

  • Occurs in the Endoplasmic Reticulum and Golgi Apparatus.
  • Thyroglobulin: A glycoprotein made up of tyrosine amino acids.
  • Transported into the lumen via exocytosis.

3. Oxidation and Transportation of Iodide

  • Enzyme: Peroxidase in the apical membrane oxidizes iodide.
  • Transport Protein: Pendrin moves oxidized iodide (now iodine) into the follicular lumen.

4. Iodination of Tyrosine

  • Iodine combines with tyrosine residues in thyroglobulin.
  • Results in:
    • Monoiodotyrosine (MIT)
    • Diiodotyrosine (DIT)
  • This process requires peroxidase and is referred to as iodination or organification.

5. Coupling Reaction

  • MIT and DIT combine to form:
    • Triiodothyronine (T3)
    • Tetraiodothyronine (T4) (or Thyroxine)
  • This step is called coupling.

6. Storage of Hormones

  • T3, T4, and reverse T3 are stored in the colloid associated with thyroglobulin for 2-3 months.

7. Secretion Process

  • Pinocytosis: Colloid droplets formed at the apical membrane.
  • Colloid droplets fuse with lysosomes containing proteases.
  • Proteases cleave T3, T4, MIT, and DIT from thyroglobulin.

8. Reutilization of Iodine

  • Deiodination: MIT and DIT are broken down into tyrosine and iodide by Diiodinase.
  • Released iodide can be reused for new thyroid hormone synthesis.

Summary of Key Steps

  1. Iodide Trapping via sodium iodide symporter.
  2. Thyroglobulin Synthesis in the ER and Golgi.
  3. Oxidation of Iodide and transportation into the lumen.
  4. Iodination of Tyrosine (formation of MIT & DIT).
  5. Coupling Reaction (formation of T3 & T4).
  6. Storage of hormones in colloid.
  7. Secretion via pinocytosis and protease activity.
  8. Deiodination of MIT and DIT for reutilization.

Conclusion

  • Understanding these steps is crucial for mastering thyroid hormone synthesis.
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