It has been postulated for decades that thyroid hormones are released from thyrocytes by simple diffusion.
Second, the genetic alterations of the PDS gene found in patients with the Pendred syndrome, which lead to a loss of the anion transport activity of pendrin and to a constant and severe hearing loss, only have a moderate impact on the thyroid functioning, generally a euthyroid goiter Vesicles carrying lysosomal enzymes 3 conveyed their content to prelysosomes or late endosomes LE and lysosomes L. The proximal region of the C-terminal half portion of Tg contains five repeats of another type of cysteine-rich motives. C and D, fluorescence images of the top C and the bottom D of the follicle after 2hr of incubation. The effects of T4 in vivo are mediated via T3 T4 is converted to T3 in target tissues. The transport of iodide from the cytoplasm to the follicle lumen should be a passive process, the electrical and concentration gradients being favorable.
Thyroxine 3,5,3',5'-tetraiodothyronine is produced by follicular cells of the thyroid gland. Identifying the donor tyrosyls has attracted considerable investigational interest over the past several decades. It can be solubilized using detergents such as deoxycholate or digitonin.
In addition to its role as component of the iodoamino acids, iodine is associated with cleavage of peptide bonds of Tg, at least in vitro A French-Canadian patient with a transient CH initially detected by neonatal screening presented a compound heterozygozity for a hemizygous missense mutation GS inherited from the father and a deletion removing the part of the gene coding for the catalytic core of Duox2 inherited from the mother.
In the thyroid, the specificity of the thyroid hormone machinery using Duox lays on TPO. Three of them had low free T4 at birth, mild thyroid enlargement. Megalin, that binds multiple unrelated ligands, interacts with Tg with a high affinity.
The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin. It has been suggested that this region of the Tg molecule may modulate its own degradation and hormone release Part of Tg molecules are conveyed via a vesicle transport system to the second type of endocytic compartments, late endosomes or prelysosomes. An extensive literature has sought to identify the iodinating species, but the issue is still not resolved see for a detailed review.
B, schematic representation of the membrane topology of the NIS polypeptide chain deduced from secondary structure prediction analyses In pig, insoluble Tg contains more iodine than did the kDa Tg, and had virtually no thyroid hormone The ER retains the abnormal proteins, which cannot then proceed for further maturation. Most of the time Duox activity is associated to a peculiar peroxidase activity like in oocyte with the ovoperoxidase involved in the fertilization process or with the lactoperoxidase in lung epithelia or in the gut ;;; The exopeptidase lysosomal dipeptidase II may also be involved in release of free T4, but from a site in Tg other than residue 5
Thyroid Hormone Synthesis Overview Thyroid Hormones are amine hormones and so their synthesis is based on the amino acid tyrosine. Correction of this defect by site-directed mutagenesis returned Tg export to normal in transfected cells. Hydrogen peroxide might be a regulatory factor of Tg expression, based on experimental work showing increased Tg promoter activity with reduced Pax-8 and TTF-1
This receptor binds Tg at acidic pH and recognizes both sugar moities and peptide determinants on Tg Glycosylation is essential for enzymatic activity In the model of Levy et al.
Thyroid Peroxidase then "organifies" the generated I2 by covalently linking it with the tyrosine residues present in Thyroglobulin. The thyroid follicles are surrounded by a lining of follicular epithelial cells and contain an acellular lumen full of proteinacious material termed the Thyroid Colloid. In humans, renal iodide clearance depends principally on glomerular filtration, without evidence of tubular secretion or of active transport with a transfer maximum Degroot LJ, Niepomniszcze H. From Pitt-Rivers, R. Human Tg may contain four different types of carbohydrate units.
The primary synthetic organ of Thyroid Hormones is the thyroid gland which produces about twenty times more T4 compared to T3. It is reasonable to think that Tg molecules following this route are the more mature molecules with a high hormone content but, this has not been firmly demonstrated. Maruo et al. These mice develop severe goitrous congenital hypothyroidism with undetectable serum T4 and high serum TSH levels
The usual acceptor for iodide is thyroglobulin, which is currently believed to be iodinated within apical secretory vesicles at the cell border just prior to liberation into the colloid, or possibly after liberation into the colloid. It was already suggested in that H2O2 would be produced at the apical plasma membrane of the thyrocyte by an enzyme that requires calcium and NADPH originating from the stimulation of the pentose phosphate pathway Some data suggest that iodide entering the gland by active transport segregates from that generated by deiodination of Tg within the gland 82; The generation of the iodothyronine residue involves the formation of an ether bond between the iodophenol part of a donor tyrosyl and the hydroxyl group of the acceptor tyrosyl Fig A French-Canadian patient with a transient CH initially detected by neonatal screening presented a compound heterozygozity for a hemizygous missense mutation GS inherited from the father and a deletion removing the part of the gene coding for the catalytic core of Duox2 inherited from the mother. A baculovirus system expressing the fragment of Tg, either normal or mutated on tyrosyl residues, showed that iodination of a fragment containing tyrosyls only at residue 5, and formed T4 as did the intact normal peptide, but this fragment could also form T4 with substitutions at residue 5 or