Functions of Triiodothyronine (T3)
Triiodothyronine (T3) is the most active form of thyroid hormone that exerts physiological actions through control of DNA transcription and protein synthesis, regulating critical metabolic functions throughout the body.
Mechanism of Action
- T3 diffuses into the cell nucleus and binds to thyroid receptor proteins attached to DNA, activating gene transcription and synthesis of messenger RNA and cytoplasmic proteins 1
- The majority of T3 (approximately 80%) is derived from T4 by deiodination in peripheral tissues, making T3 the predominant active hormone at the nuclear receptor 1, 2
- T3 binds to nuclear thyroid receptors with higher affinity than T4, making it more potent (approximately 4 times more biologically active than T4) 1
Metabolic Functions
- T3 regulates daily rhythms in glucose metabolism, with faster glucose clearance occurring during the early active phase 3
- T3 controls lipolysis and fatty acid oxidation during fasting states, influencing serum triglyceride levels and overall lipid metabolism 3
- T3 increases the force and speed of systolic contraction and the speed of diastolic relaxation in cardiac tissue, affecting heart function 4
Tissue-Specific Functions
Cardiovascular System
- T3 decreases systemic vascular resistance, including coronary vascular tone 4
- T3 increases resting heart rate and left ventricular contractility 4
- T3 enhances isovolumic ventricular relaxation, improving cardiac function 4
Thyroid Gland
- T3 is involved in the tissue conversion of T4 to T3 within the thyroid gland itself 4
- T3 participates in thyroid-stimulating hormone (TSH) secretion regulation through negative feedback 4
Bone Development
- T3 is crucial for bone health, influencing the production of collagen type I through hydroxylases that require iron for their catalytic activity 4
- T3 affects bone mineral density and overall bone health 4
Skin
- T3 is essential for skin homeostasis, regulating keratinocyte proliferation and functional differentiation 5
- Alterations in T3 levels can lead to skin conditions such as alopecia, dermatitis, and other dermatological manifestations 5
Regulation and Metabolism
- T3 production is primarily regulated by thyroid-stimulating hormone (TSH) from the pituitary gland 6
- T3 shows distinct daily rhythmic patterns that differ between diurnal humans and nocturnal rodents 3
- T3 has a shorter half-life (≤2 days) compared to T4 (6-7 days), allowing for more rapid changes in metabolic activity 1
- T3 is highly protein-bound (99.5%) in circulation, with only the unbound hormone being metabolically active 1
Clinical Implications
- Abnormal T3 levels can lead to thyroid dysfunction, manifesting as either hypothyroidism (insufficient T3) or hyperthyroidism (excess T3) 6
- T3 deficiency can result in decreased metabolic rate, while excess T3 increases metabolic rate 3
- Iron deficiency can impair the conversion of T4 to T3, affecting thyroid function 4, 6
- Selenium is required for the deiodination of T4 to T3 via the selenoenzyme Type 1 5'-deiodinase 6
Alternate Metabolic Pathways
- T3 can undergo sulfation and glucuronidation of the phenolic hydroxyl group, providing additional mechanisms for regulating the supply of active hormone 2
- T3 can be converted to diiodothyronine (T2) through further deiodination 2
- T3 can undergo oxidative deamination and decarboxylation of the alanine side chain to form iodothyroacetic acids 2