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 H 2 O 2 , 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 H 2 O 2 -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.
Gillotay et al. (Thu,) studied this question.