Role of thyroglobulin endocytic pathways in the control of thyroid hormonerelease

Thyroglobulin (Tg), the thyroid hormone precursor, is synthesized by thyroc ytes and secreted into the colloid. Hormone release requires uptake of Tg b y thyrocytes and degradation in lysosomes. This process must be precisely r egulated. Tg uptake occurs mainly by micropinocytosis, which can result fro m both fluid-phase pinocytosis and receptor-mediated endocytosis. Because T g is highly concentrated in the colloid, fluid-phase pinocytosis or low-aff inity receptors should provide sufficient Tg uptake for hormone release; hi gh-affinity receptors may serve to target Tg away from lysosomes, through r ecycling into the colloid or by transcytosis into the bloodstream. Several apical receptors have been suggested to play roles in Tg uptake and intrace llular trafficking. A thyroid asialoglycoprotein receptor may internalize a nd recycle immature forms of Tg back to the colloid, a function also attrib uted to an as yet unidentified N-acetylglucosamine receptor. Megalin mediat es Tg uptake by thyrocytes, especially under intense thyroid-stimulating ho rmone stimulation, resulting in transcytosis of Tg from the colloid to the bloodstream, a function that prevents excessive hormone release.