Triiodothyronine (T3)
Also known as: T3, liothyronine, reverse T3, rT3
The biologically active thyroid hormone — 3–5 times more potent than T4 — produced mostly by peripheral deiodination of T4 and acting on nuclear receptors to raise metabolic rate and drive growth and development.
Overview
Only ≈20 % of circulating T3 is secreted directly by the thyroid; ≈80 % comes from outer-ring deiodination of T4 in liver, kidney and muscle. T3 is less tightly protein-bound (free ≈0.3 %), has a half-life of ≈1 day and binds nuclear thyroid-hormone receptors (TRα, TRβ) with ≈10-fold higher affinity than T4. The receptors sit on thyroid response elements of DNA as heterodimers with the retinoid X receptor; binding T3 releases co-repressors, recruits co-activators and changes gene transcription.
Actions: (1) metabolism — increased Na⁺/K⁺-ATPase activity, oxygen consumption, basal metabolic rate and heat production (uncoupling protein-1 in brown fat); increased glucose absorption, glycogenolysis, gluconeogenesis, lipolysis and LDL-receptor expression (low cholesterol); (2) cardiovascular — increased β1-adrenergic receptor number, α-myosin heavy chain and SERCA2, giving tachycardia, increased contractility and cardiac output, and reduced systemic vascular resistance; (3) growth and development — essential with GH for linear growth and skeletal maturation, and for fetal and neonatal brain development (neuronal migration, myelination); (4) other — increased gut motility, ventilatory drive, bone turnover, and speed of muscle relaxation.
- Location
Source: thyroid follicular cells (≈20 %) and peripheral tissues by deiodination of T4 (≈80 %). Targets: nearly all tissues.
Function
- Raises basal metabolic rate, oxygen consumption and thermogenesis.
- Increases heart rate, contractility and cardiac output; sensitises tissues to catecholamines.
- Essential for CNS development and skeletal growth and maturation.
- Regulates carbohydrate, lipid and protein metabolism.
- Physiology
Class: iodothyronine (amine with steroid-like behaviour). Receptor: nuclear TRα/TRβ (heterodimer with RXR). Half-life ≈1 day. Free fraction ≈0.3 %; free T3 ≈3–7 pmol/L. Reverse T3 (from type 3 deiodinase) is inactive.
- Regulation
Generation of T3 is regulated tissue by tissue through deiodinases: fasting, critical illness, glucocorticoids, amiodarone, propranolol and propylthiouracil reduce T4→T3 conversion, while hypothyroidism up-regulates type 2 deiodinase in the brain to protect neural T3.
Clinical significance
Non-thyroidal illness ("sick euthyroid")
In starvation and severe illness, T3 falls and reverse T3 rises (reduced type 1 and increased type 3 deiodinase), often with normal or low TSH — an adaptive reduction in metabolic rate that is not treated with thyroid hormone.
T3 toxicosis
Early Graves disease or a toxic nodule may raise T3 before T4; measure free T3 when TSH is suppressed but free T4 is normal.
Cretinism (congenital hypothyroidism)
Lack of thyroid hormone in fetal/neonatal life causes intellectual disability, short stature, coarse facies, macroglossia, umbilical hernia and prolonged jaundice — preventable by newborn screening and early levothyroxine.
Test yourself
Which hormone acts mainly through an intracellular (nuclear) receptor?
- Glucagon
- Triiodothyronine (T3)
- Epinephrine
- Insulin
Answer: Triiodothyronine (T3)
Thyroid hormones enter cells via transporters (e.g. MCT8) and bind nuclear thyroid-hormone receptors that act as transcription factors. Glucagon and epinephrine use GPCRs (cAMP); insulin uses a receptor tyrosine kinase.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.