Back to Search Start Over

The role of thyroglobulin in thyroid hormonogenesis.

The role of thyroglobulin in thyroid hormonogenesis.

Authors :
Citterio CE
Targovnik HM
Arvan P
Source :
Nature reviews. Endocrinology [Nat Rev Endocrinol] 2019 Jun; Vol. 15 (6), pp. 323-338.
Publication Year :
2019

Abstract

In humans, the thyroid hormones T <subscript>3</subscript> and T <subscript>4</subscript> are synthesized in the thyroid gland in a process that crucially involves the iodoglycoprotein thyroglobulin. The overall structure of thyroglobulin is conserved in all vertebrates. Upon thyroglobulin delivery from thyrocytes to the follicular lumen of the thyroid gland via the secretory pathway, multiple tyrosine residues can become iodinated to form mono-iodotyrosine (MIT) and/or di-iodotyrosine (DIT); however, selective tyrosine residues lead to preferential formation of T <subscript>4</subscript> and T <subscript>3</subscript> at distinct sites. T <subscript>4</subscript> formation involves oxidative coupling between two DIT side chains, and de novo T <subscript>3</subscript> formation involves coupling between an MIT donor and a DIT acceptor. Thyroid hormone synthesis is stimulated by TSH activating its receptor (TSHR), which upregulates the activity of many thyroid gene products involved in hormonogenesis. Additionally, TSH regulates post-translational changes in thyroglobulin that selectively enhance its capacity for T <subscript>3</subscript> formation - this process is important in iodide deficiency and in Graves disease. 167 different mutations, many of which are newly discovered, are now known to exist in TG (encoding human thyroglobulin) that can lead to defective thyroid hormone synthesis, resulting in congenital hypothyroidism.

Details

Language :
English
ISSN :
1759-5037
Volume :
15
Issue :
6
Database :
MEDLINE
Journal :
Nature reviews. Endocrinology
Publication Type :
Academic Journal
Accession number :
30886364
Full Text :
https://doi.org/10.1038/s41574-019-0184-8