Endocrine Abstracts

Objective: The autoregulatory response of thyroid follicles to excess iodine involves different steps and processes, most notably the acute inhibition of thyroglobulin (Tg) iodination called the Wolff-Chaikoff phenomenon, and the subsequent downregulation of the sodium-iodide symporter (NIS) during the so-called escape from the Wolff-Chaikoff phenomenon. The molecular mechanisms involved in these phenomena are still incompletely understood. In previous studies, we have found paradoxical autoregulatory responses in mice with altered redox signaling. Specifically, mice lacking the ubiquitous transcription factor Nrf2 that mediates the transcriptional antioxidant response show increased levels of thyroidal iodinated Tg (Tg-I) at baseline compared to wild-type (WT) mice, as well as a paradoxical increase in thyroidal Tg-I in response to iodine excess. We aimed to test the dependence of autoregulatory responses on the oxidative status of follicles.

Methods: WT and Nrf2 KO mice were treated (or not) via the drinking water for 2 weeks with N-acetyl-cysteine (NAC) that promotes scavenging of intracellular oxidants. During the second week, half of the mice were treated with excess iodine (sodium iodide 0.05%) in the drinking water (total of 8 × 8=64 mice). Mice were then sacrificed, and the thyroid, pituitary and serum were harvested for analysis.

Results: Iodine treatment increased pituitary beta-TSH mRNA levels in all mice compared to respective untreated controls. Iodine-treated Nrf2 KO mice showed significantly higher pituitary beta-TSH mRNA levels than respective WT mice; this difference was completely abolished by NAC treatment. Iodine-treated Nrf2 KO mice were also the only group in which NAC treatment did not decrease the levels of Tg-I compared to no NAC treatment. In contrast, the response of NIS to excess iodine was independent of both genotype and NAC treatment.

Conclusions: Thyroid autoregulation in response to excess iodine comprises an oxidation-dependent component (inhibition of Tg iodination) and an oxidation-independent one (NIS downregulation).