NIH R01 · 2025
Thyroid Hormone Signaling in a Triiodothyronine-Only Hormonal Environment
PROJECT SUMMARY/ ABSTRACT Thyroid hormones (THs), T4 and T3, are synthesized in the thyroid gland under the influence of TSH, and play a critical role in regulating thermogenesis, energy expenditure (EE), and even thyroid function. T4 is primarily formed at the N-terminus of thyroglobulin (Tg), while de novo synthesis of T3 (the most active TH) occurs mostly at the C-terminal ChEL domain of Tg. In the body, all T4 is produced in the thyroid, while T3 is generated largely through deiodination of T4 in various tissues. Hypothyroidism, affecting 5-10% of the population, often presents with goiter, reduced EE, and weight gain. Although T4 treatment normalizes TSH in hypothyroid patients, it…
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