The role of Nrf2 in thyroid maturation and hormone synthesis in vertebrate models.
Gillotay Pierre, Bangru Sushant, Dassy Benjamin, Haerlingen Benoit, Shankar Meghna P, Fonseca Barbara F, Ziros Panos G, Singh Sumeet P, Sykiotis Gerasimos P, Romitti Mirian, Costagliola Sabine
Abstract
In vertebrates, the thyroid gland synthesizes hormones that act on almost all tissues and are essential for normal growth and metabolism. Thyroid hormone production relies on iodination of thyroglobulin and requires H2O2, which contributes to a relatively high basal oxidative stress in the thyroid that must be tightly controlled to prevent cellular damage. The thyroid has efficient antioxidant and detoxifying enzymes that help it resist H2O2-induced oxidative stress maintaining the homeostasis necessary for hormone synthesis. By regulating the expression of genes involved in cellular detoxification, NRF2 acts as a master regulator of the cellular defense against oxidative stress. Using zebrafish embryos and mouse ESC-derived thyroid organoids, we generated nrf2a/Nrf2 loss-of-function and identified a common dyshormonogenesis phenotype. Although in zebrafish, the driving mechanisms are possibly related to thyroglobulin iodination defects, in thyroid organoids, it is likely due to a reduction in Tg production, consequently affecting folliculogenesis and thyroid hormone production.
Key Findings
- NRF2 acts as a master regulator of cellular defense against oxidative stress in the thyroid gland.
- Loss of NRF2 function in zebrafish and mouse thyroid models leads to dyshormonogenesis.
- NRF2 deficiency causes defects in thyroglobulin iodination in zebrafish and reduces thyroglobulin production in mouse thyroid organoids, impairing folliculogenesis and thyroid hormone synthesis.
Clinical Significance
Understanding NRF2's role in thyroid oxidative stress regulation and hormone synthesis could inform therapeutic strategies for thyroid dysfunctions related to oxidative damage and hormone production defects.
Citation
Gillotay Pierre, Bangru Sushant, Dassy Benjaminet al.. The role of Nrf2 in thyroid maturation and hormone synthesis in vertebrate models. Life science alliance. 2026-Jul.