Thyroid follicle

Each follicle (tens to hundreds of micrometres across) is a closed sac of thyrocytes resting on a basal lamina, with their apical microvilli facing the colloid and their bases facing fenestrated capillaries. Colloid is mainly thyroglobulin (Tg), a large (660 kDa) glycoprotein containing ≈130 tyrosine residues, of which only a few are used to make hormone. Follicle height reflects activity: flat cells with abundant colloid in the resting gland; tall columnar cells with scalloped, scanty colloid when stimulated (Graves disease).

Thyroid hormone synthesis runs in eight steps: (1) Iodide trapping — the basolateral Na⁺/I⁻ symporter (NIS) concentrates iodide 20–40-fold, powered by the Na⁺ gradient; (2) iodide crosses the apical membrane into the colloid via pendrin (and anoctamin-1); (3) thyroglobulin is synthesised on rough ER and exocytosed into the lumen; (4) oxidation of iodide by thyroid peroxidase (TPO) using H₂O₂ generated by DUOX2; (5) organification — TPO iodinates tyrosyl residues of Tg to form monoiodotyrosine (MIT) and diiodotyrosine (DIT); (6) coupling, also by TPO: DIT + DIT → T4, MIT + DIT → T3, still attached to Tg and stored as colloid; (7) on TSH stimulation, thyrocytes endocytose colloid, droplets fuse with lysosomes and proteases release free T4 and T3, which leave across the basolateral membrane (MCT8); (8) free MIT and DIT are deiodinated by iodotyrosine deiodinase (DEHAL1) and the iodide is recycled.