Deiodinases control local cellular and systemic thyroid hormone availability.
Level 5 - mechanism / opinion, no new human data
Narrative review of biochemical and mechanistic data
PubMed 36206932 · doi:10.1016/j.freeradbiomed.2022.09.024
What was done
This narrative review synthesized biochemical characteristics, reaction mechanisms, and regulatory factors of the iodothyronine deiodinase family of selenoproteins (DIO1, DIO2, and DIO3), which control local and systemic activation of thyroxine (T4) to triiodothyronine (T3) and their subsequent inactivation.
What was found
The abstract provides no numerical data. Mechanistically, DIO1 and DIO2 activate T4 into active T3, whereas DIO3 inactivates both T4 and T3. Deiodinases display species- and tissue-specific regulation governed by thyroid hormone levels, cytokines, growth factors, and pathophysiological states. Because DIOs hold high priority for selenium allocation, their expression and translation are only modestly impacted by selenium status except during severe deficiency. Genetic variants, SNPs, rare mutations, endocrine disruptors, and pharmacological inhibitors also alter DIO activity, and a crystal structure has been resolved for DIO3.
Why it matters
Understanding the biochemical mechanisms of deiodinases clarifies how tissues independently regulate local thyroid hormone signaling and informs the development of isozyme-selective drugs.
Limits
The abstract describes a broad narrative synthesis without systematic search criteria, meta-analysis, or novel human clinical outcome data. No quantitative effect sizes or sample sizes are reported.
Cited by
- supports T4 is an inactive thyroid hormone, whereas T3 is the active thyroid hormone.