1. Academic Validation
  2. The role of thyroglobulin in thyroid hormonogenesis

The role of thyroglobulin in thyroid hormonogenesis

  • Nat Rev Endocrinol. 2019 Jun;15(6):323-338. doi: 10.1038/s41574-019-0184-8.
Cintia E Citterio 1 2 Héctor M Targovnik 1 2 Peter Arvan 3
Affiliations

Affiliations

  • 1 Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología/Cátedra de Genética, Buenos Aires, Argentina.
  • 2 CONICET-Universidad de Buenos Aires, Instituto de Inmunología, Genética y Metabolismo (INIGEM), Buenos Aires, Argentina.
  • 3 Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, MI, USA. parvan@umich.edu.
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.

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