Deiodinases control local cellular and systemic thyroid hormone availability

Area of Science:

• Biochemistry
• Endocrinology
• Nutritional Science

Background:

• Iodothyronine deiodinases (DIOs) are selenoproteins controlling thyroid hormone (T4, T3) availability.
• DIO1 and DIO2 activate T4 to T3, while DIO3 inactivates T4 and T3.
• DIOs exhibit species-specific expression, regulation, and function.

Purpose of the Study:

• To review the biochemical characteristics and reaction mechanisms of DIO selenoproteins.
• To explore the relationships between DIOs and their importance in T3 provision.
• To discuss factors impacting DIO functions.

Main Methods:

• Literature review of biochemical characteristics, reaction mechanisms, and regulation of DIOs.
• Analysis of species-specific expression, function, and inhibitor sensitivities.
• Examination of the impact of nutritional, pharmacological, and environmental factors.

Main Results:

• DIOs are critical for systemic and local thyroid hormone availability.
• Thyroid hormone status, growth factors, and cytokines are key regulators.
• Selenium status has a modest impact, with function impaired only in severe deficiency.
• DIO variants and polymorphisms have been identified, with drug development ongoing.

Conclusions:

• DIOs are essential selenoproteins with diverse roles in thyroid hormone metabolism.
• Understanding DIOs is crucial for managing thyroid hormone-related conditions.
• Further research into DIO isozyme-selective drugs and modulators is warranted.