Low blood levels of the thyroid hormones — triiodothyronine or T₃ and thyroxine or T₄ —signal the hypothalamus to release the thyrotropin-releasing hormone or TRH.

TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone or TSH into the bloodstream.

Upon reaching the thyroid gland, TSH stimulates the active uptake of iodide ions from the blood by the follicular cells.

The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then added to tyrosine residues of the thyroglobulin protein stored in the lumen colloid, forming monoiodotyrosine or T₁ and diiodotyrosine or T₂.

The coupling of one molecule of T_1, with T₂ forms a T₃ molecule, whereas two T₂ molecules combine together to form T₄.

Finally, endocytosis and enzymatic cleavage releases the T₃ and T₄ in the follicular cells. These hormones then cross into the blood vessel for transport to target tissues.

An increase in blood levels of T₃ and T₄ temporarily inhibits the production of TRH and TSH, regulating the level of thyroid hormones in the body.