Synthesis of Thyroid Hormone

• Synthesis of thyroid hormone

  1. Thyroid gland located in anterior neck

  2. Thyroid follicles are structural and functional unit

  3. Hypothalamic-pituitary-thyroid (HPT) axis

  4. Hypothalamus secretes thyrotropin-releasing hormone (TRH)

  5. TRH stimulates anterior pituitary to secrete thyroid stimulating hormone (TSH)

  6. TSH binds to receptors on thyroid follicular cells

  7. Activates G-protein and adenylate cyclase

  8. Increases cyclic AMP

  9. Activates protein kinase A

  10. Phosphorylates transcription factors

  11. Stimulates genes to produce thyroglobulin protein

  12. Thyroglobulin packaged and secreted into follicle lumen

  13. Iodide transported into follicular cells

  14. Thyroid peroxidase enzyme iodizes thyroglobulin
• Thyroglobulin


  Protein that is the basic unit of thyroid hormone
• Iodide


  Iodine ion that is transported into follicular cells and used to iodize thyroglobulin
• Pendrin


  Protein that pumps iodide out of follicular cells into the follicle lumen
• Thyroid peroxidase (TPO)


  Enzyme that iodizes thyroglobulin in the follicle lumen
• Mutation in pendrin protein can alter thyroid hormone production
• Pin drin


  Pumps the iodide out into the luminal space
• Thyroid peroxidase (TPO)


  Enzyme that converts iodide to iodine by oxidation
• Iodide oxidation


  Iodide is kicked hard by TPO, knocking off electrons and converting it to iodine
• Iodination


  TPO puts the iodine onto tyrosine amino acids of thyroglobulin
• Mono iodotyrosine (MIT)


  Tyrosine with one iodine atom
• Di iodotyrosine (DIT)


  Tyrosine with two iodine atoms
• Coupling


  TPO couples MIT and DIT to form T3 (tri-iodothyronine) and T4 (thyroxine)
• T3 and T4


  Thyroid hormones
• Endocytosis


  Thyroglobulin containing T3 and T4 is brought into the follicular cell in a vesicle
• Lysosomal enzyme cleavage


  Lysosomal enzymes cleave T3 and T4 from thyroglobulin
• Exocytosis


  T3 and T4 are released from the follicular cell into the bloodstream
• Thyroxine binding globulin (TBG)


  Protein that transports T3 and T4 in the blood
• Steps in thyroid hormone synthesis

  • TRH release
  • TSH stimulation
  • Thyroglobulin synthesis
  • Iodide trapping
  • Iodide oxidation
  • Iodination
  • Coupling
  • Endocytosis
  • Lysosomal cleavage
  • Exocytosis