Endocrinology | Synthesis of Thyroid Hormone

The video introduces the synthesis of thyroid hormone within the thyroid gland, located in the anterior neck. It highlights the importance of thyroid follicles, which are the structural and functional units. The process begins with the Hypothalamic-Pituitary-Thyroid (HPT) axis. The hypothalamus releases Thyrotropin-Releasing Hormone (TRH) from the paraventricular nucleus, which stimulates the anterior pituitary's thyrotropes to release Thyroid Stimulating Hormone (TSH).

TSH binds to receptors on the follicular cells of the thyroid gland, activating an intracellular pathway involving a G-stimulatory protein and adenylate cyclase. This leads to the conversion of ATP to cyclic AMP, which in turn activates Protein Kinase A. Protein Kinase A phosphorylates transcription factors, stimulating gene expression for a specific protein. This protein is then synthesized in the rough ER, modified in the Golgi apparatus, packaged into vesicles, and exocytosed into the follicular lumen. This secreted protein is called thyroglobulin, which contains tyrosine amino acids, a basic unit for thyroid hormone.

For thyroid hormone synthesis, iodine is crucial. It circulates in the blood as iodide (I-) and is in high concentration outside the follicular cell but low inside. Iodide enters the follicular cell against its concentration gradient via secondary active transport with sodium, a process called iodide trapping. Inside the cell, iodide is transported into the follicular lumen by a protein called pendrin. Once in the lumen, an enzyme called thyroid peroxidase (TPO) oxidizes iodide (I-) into iodine (I0), losing an electron. This step is known as iodide oxidation.

Thyroid peroxidase then catalyzes the iodination of tyrosine residues on the thyroglobulin protein. Adding one iodine to a tyrosine forms monoiodotyrosine (MIT), and adding two iodines forms diiodotyrosine (DIT). Following iodination, TPO also mediates the coupling of these iodinated tyrosines. Coupling one MIT with one DIT forms Triiodothyronine (T3), which has three iodine atoms. Coupling two DITs forms Thyroxine (T4), with four iodine atoms. T3 and T4 are collectively known as thyroid hormone.

The thyroglobulin colloid, now containing T3 and T4, is reabsorbed into the follicular cell via endocytosis. Lysosomal enzymes within the cell then fuse with the endocytotic vesicles and cleave T3 and T4 from the thyroglobulin, isolating the active hormones. Finally, T3 and T4 are released into the bloodstream through exocytosis. Because T3 and T4 are not water-soluble, they bind to transport proteins in the blood, primarily thyroxine-binding globulin (TBG), synthesized by the liver, to be transported to target tissues.

The video concludes with a recap of the 10 key steps: 1) TRH release from the hypothalamus, 2) TSH release from the anterior pituitary, 3) TSH stimulates thyroglobulin synthesis, 4) Iodide trapping, 5) Oxidation of iodide, 6) Iodination of tyrosine amino acids, 7) Coupling of DITs and MITs to form T3 and T4, 8) Endocytosis of thyroglobulin with T3 and T4, 9) Lysosomal enzymes cleave T3 and T4, and 10) Exocytosis of T3 and T4 into blood plasma where they bind to thyroxine-binding globulins.