Document Type
Article
Publication Date
3-18-2019
Abstract
In humans, the thyroid hormones T3 and T4 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 T4 and T3 at distinct sites. T4 formation involves oxidative coupling between two DIT side chains, and de novo T3 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 T3 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.
Recommended Citation
Citterio, C.E., Targovnik, H.M. & Arvan, P. The role of thyroglobulin in thyroid hormonogenesis. Nat Rev Endocrinol 15, 323–338 (2019). https://doi.org/10.1038/s41574-019-0184-8
Copyright
Springer
Included in
Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Other Pharmacy and Pharmaceutical Sciences Commons
Comments
This article was originally published in Nature Reviews Endocrinology, volume 15, in 2019. https://doi.org/10.1038/s41574-019-0184-8
The Link to Full Text button above directs users to a free read-only version of the article.