Triiodothyronine (T3) Associated Diseases and Disorders
Physiological functions of triiodothyronine (T₃), the biologically active thyroid hormone.
T₃ is the principal active thyroid hormone that regulates basal metabolism, growth, CNS development, thermogenesis, cardiovascular function, and potentiates catecholamine sensitivity, affecting almost every tissue.
🔹 What is triiodothyronine (T₃)?
- T₃ is the primary active thyroid hormone at the cellular level.
- Most circulating T₃ (~80%) is produced by peripheral deiodination of T₄ (thyroxine).
- It binds to thyroid hormone receptors (TRs) in the nucleus and regulates transcription of many target genes.
🔹 Core physiological functions of T₃
| System / Domain | Physiological Function | Mechanism / Outcome |
| ⚡ Basal metabolic rate (BMR) | Increases metabolic rate in almost all tissues | Stimulates mitochondrial biogenesis, increases Na⁺/K⁺-ATPase activity, enhances ATP turnover and oxygen consumption, generates heat (thermogenesis) |
| 🧠 CNS development and function | Essential for brain maturation (especially fetal and early postnatal) | Promotes neuronal differentiation, myelination, axonal growth, synaptogenesis |
| 🦴 Growth & skeletal development | Supports linear growth and bone maturation | Synergizes with growth hormone (GH) and insulin-like growth factor 1 (IGF-1) |
| ❤️ Cardiovascular system | Maintains normal heart rate and cardiac output | Increases β-adrenergic receptor expression, enhances myocardial contractility and diastolic relaxation, increases cardiac output |
| 🍽️ Carbohydrate metabolism | Stimulates glucose turnover | ↑ Gluconeogenesis, ↑ glycogenolysis, ↑ intestinal glucose absorption |
| 🩸 Lipid metabolism | Mobilizes lipid stores | ↑ Lipolysis, ↓ cholesterol via ↑ LDL receptor expression, ↑ fatty acid oxidation |
| 🧬 Protein metabolism | Controls protein turnover | Stimulates both protein synthesis and breakdown (net effect depends on T₃ levels) |
| 🛌 Neuromuscular function | Regulates muscle tone and reflexes | Influences contractile proteins and neuromuscular transmission |
| 🦠 Thermogenesis | Critical for heat production | Stimulates uncoupling proteins and mitochondrial function in brown adipose tissue |
| 🛡️ Sympathetic nervous system modulation | Potentiates catecholamine action | Upregulates β-adrenergic receptors in heart and other tissues; explains “adrenergic-like” symptoms of hyperthyroidism |
🔹 Developmental roles
✅ In fetal and infant development:
- T₃ is essential for:
- Normal brain development (deficiency → irreversible intellectual disability)
- Skeletal maturation
- Lung development and surfactant production
🔹 Molecular mechanism
- T₃ binds nuclear thyroid hormone receptors (TRα, TRβ) → receptor heterodimerizes with RXR → binds thyroid hormone response elements (TREs) on DNA → regulates transcription.
- Compared to T₄, T₃ has about 3–5 times greater receptor affinity and activity.