T3 is the true hormone. Its effects on target tissues are roughly four times more potent than those of T4. Of the thyroid hormone that is produced, just about 20% is T3, whereas 80% is produced as T4. Roughly 85% of the circulating T3 is later formed in the liver and anterior pituitary by removal of the iodine atom from the carbon atom number five of the outer ring of T4. In any case, the concentration of T3 in the human blood plasma is about one-fortieth that of T4. The half-life of T3 is about 2 – 0.5 days. The half-life of T4 is about 6.5 days.
T3 is the more metabolically active hormone produced from T4. T4 is deiodinated by three deiodinase enzymes to produce the more-active triiodothyronine:
- Type I present in liver, kidney, thyroid, and (to a lesser extent) pituitary; it accounts for 80% of the deiodination of T4.
- Type II present in CNS, pituitary, brown adipose tissue, and heart vessel, which is predominantly intracellular. In the pituitary, it mediates negative feedback on thyroid-stimulating hormone.
- Type III present in placenta, CNS, and hemangioma. This deiodinase converts T4 into reverse T3, which, unlike T3, is inactive.
T4 is synthesised in the thyroid gland follicular cells as follows.
- The sodium-iodide symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodine ion. This is a secondary active transporter that utilises the concentration gradient of Na+ to move I− against its concentration gradient.
- I− is moved across the apical membrane into the colloid of the follicle.
- Thyroperoxidase oxidises two I− to form I2. Iodide is non-reactive, and only the more reactive iodine is required for the next step.
- The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid.
- Thyroid-stimulating hormone (TSH) released from the anterior pituitary gland binds the TSH receptor (a Gs protein-coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.
- The endocytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin.
- These vesicles are then exocytosed, releasing the thyroid hormones.