Overview
This lecture explains the step-by-step synthesis of thyroid hormones (T3 and T4) in the thyroid gland, emphasizing the HPT axis, molecular mechanisms, and critical enzymes involved.
Structure and Function of the Thyroid Gland
- The thyroid gland is a butterfly-shaped organ located below the larynx in the anterior neck.
- Thyroid follicles are the basic structural and functional units of the gland.
- Follicular cells (simple cuboidal epithelium) surround the follicle and produce thyroid hormone.
Hypothalamic-Pituitary-Thyroid (HPT) Axis
- The hypothalamus releases thyrotropin-releasing hormone (TRH) from the paraventricular nucleus.
- TRH stimulates thyrotropes in the anterior pituitary to secrete thyroid-stimulating hormone (TSH).
- TSH binds to receptors on thyroid follicular cells, activating intracellular signaling.
Intracellular Signaling and Thyroglobulin Synthesis
- TSH binding activates a Gs protein, which activates adenylate cyclase to convert ATP to cAMP.
- cAMP activates protein kinase A, which phosphorylates transcription factors.
- Phosphorylated transcription factors stimulate transcription and translation of thyroglobulin (Tg).
- Tg is packaged in the Golgi, exocytosed into the follicular lumen, forming the colloid.
Iodide Uptake and Oxidation
- Iodide is transported into follicular cells via secondary active transport with sodium (NIS symporter).
- Iodide is transported out of the cell into the lumen by the pendrin protein.
- Thyroid peroxidase (TPO) oxidizes iodide (I-) to iodine (I0) in the lumen.
Hormone Assembly: Iodination and Coupling
- Iodine attaches to tyrosine residues on thyroglobulin, forming MIT (monoiodotyrosine) and DIT (diiodotyrosine) through iodination.
- Coupling reactions: DIT + DIT forms T4 (thyroxine), and MIT + DIT forms T3 (triiodothyronine).
Release of T3 and T4
- Thyroglobulin with T3 and T4 is endocytosed back into the follicular cell.
- Lysosomal enzymes cleave T3 and T4 from thyroglobulin.
- Free T3 and T4 are exocytosed into the bloodstream.
Transport in Blood
- T3 and T4 are transported in blood bound to thyroxine-binding globulin (TBG) due to their low water solubility.
Key Terms & Definitions
- Thyrotropin-Releasing Hormone (TRH) — hormone from hypothalamus stimulating TSH release.
- Thyroid-Stimulating Hormone (TSH) — hormone from pituitary stimulating thyroid hormone synthesis.
- Thyroglobulin (Tg) — protein precursor for thyroid hormone synthesis.
- Iodination — addition of iodine to tyrosine residues.
- Thyroid Peroxidase (TPO) — enzyme catalyzing iodide oxidation and iodination.
- MIT/DIT — monoiodotyrosine/diiodotyrosine, intermediates in hormone synthesis.
- Thyroxine (T4) — primary thyroid hormone produced, contains four iodines.
- Triiodothyronine (T3) — more active thyroid hormone, contains three iodines.
- Thyroxine-Binding Globulin (TBG) — plasma protein transporting T3 and T4.
Action Items / Next Steps
- Review the steps of thyroid hormone synthesis in order.
- Prepare for the next lecture on the effects of thyroid hormone on target organs.