•Fig. 42.4 Iodinedistributionandturnoverinhumans.HI,hormone-associatediodine.Stool 10 µg HIUrine 390 µg ITissues Thyroid Extracellular fluid 10 µg HI60 µg HI80 µg I400 µg IDiet 320 µg I20 µg I50 µg I thyroglobulin. This entire sequence of reactions is catalyzed by thyroid peroxidase (TPO), an enzyme complex that spans the apical membrane. The immediate oxidant (electron acceptor) for the reaction is hydrogen peroxide (H2O2). Generation of H2O2 in the follicular lumen is catalyzed by dual oxidases (DUOX1, DUOX2) that are also localized in the apical plasma membrane.
When iodide availability is restricted, formation of T3 is favored. Because T3 is three times as potent as T4, this response provides more active hormone per molecule of organified iodide. The proportion of T3 also increases when the thyroid gland is hyperstimulated by TSH or other activators.
Secretion of Thyroid Hormones
Once thyroglobulin has been iodinated, it is stored in the lumen of the follicle as colloid (see
Fig. 42.2 ). Release of T4 and T3 into the bloodstream is initiated by endocytosis of colloid from the follicular lumen by the processes of macroand micropinocytosis. Endocytotic vesicles then fuse with lysosomes and thyroglobulin is degraded (
Fig.
42.7
Fig. 42.5 ). MIT and DIT molecules, which also are released during proteolysis of thyroglobulin, are rapidly deiodinated within the follicular cell by the enzyme iodotyrosine deiodinase (see
Fig. 42.5 ). This deiodinase is specific for MIT and DIT and cannot use T4 and T3 as substrates. The iodide is then recycled into synthesis of T4 and T3. Amino acids from the digestion of thyroglobulin reenter the intrathyroidal amino acid pool and can be reused for protein synthesis. Only minor amounts of intact thyroglobulin leave the follicular cell under normal circumstances. Enzymatically released T4 and T3 are transported across the basal side of the cell and enter the blood.
•Fig. 42.5 Synthesisandsecretionofthyroidhormonesbythethyroidepithelialcell.
I I I I 3,5,3¢ 5¢ -Tetraiodothyronine (thyroxine, or T4) NH2 CH2CHCOOHHO O I I NH2 CH2CHCOOHHO O I NH2 CH2CHCOOHHO I NH2 CH2CHCOOH + I I DIT DIT NH2 CH2CHCOOH + I I NH2 CH2CHCOOHHO I Diiodotyrosine (DIT) or NH2 CH2CHCOOHHO Monoiodotyrosine (MIT) NH2 CH2CHCOOHHO Tyrosine NH2 CH2CHCOOHI2 + HO
DIT MIT 3,5,3¢ -Triiodothyronine (T3) •Fig. 42.6 Reactionsinvolvedinthegenerationofiodide,MIT,DIT,T3,andT4.