Summary
Highlights
Thyroid hormone (T4 and T3) circulates in the bloodstream bound to thyroxine-binding globulins. T4, the major component, enters target cells and is converted to the active form, T3, by the enzyme 5'-deiodinase. T3 then binds to a receptor, forming a complex with retinoic acid, which acts as a transcription factor to stimulate specific gene sequences, leading to protein synthesis, particularly sodium-potassium ATPases. This process increases energy consumption, leading to a decrease in cellular ATP, which in turn boosts metabolism, oxygen usage, and heat production. Thyroid hormone also increases the number and size of mitochondria.
Thyroid hormone primarily increases blood glucose levels by stimulating glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis (formation of glucose from non-carbohydrate sources like glycerol, amino acids, and lactate). It also increases the number of LDL receptors on liver cells, leading to increased uptake of LDL from the blood and thus lowering blood LDL levels.
Thyroid hormone enhances cardiac contractility by increasing the expression of beta-1 adrenergic receptors in myocardial cells. This leads to increased sensitivity to epinephrine and norepinephrine, resulting in increased stroke volume, cardiac output, and blood pressure. It also acts on the SA and AV nodes, increasing heart rate and blood pressure by the same mechanism.
Thyroid hormone is crucial for CNS development, promoting dendrite formation, myelination (leading to faster action potentials), and the number of synapses. In hyperthyroidism, this can manifest as anxiety and irritability due to heightened neurological activity.
Thyroid hormone regulates the balance between osteoclast (bone resorption) and osteoblast (bone deposition) activity, playing a role in bone remodeling. It stimulates interstitial growth at epiphyseal plates, contributing to bone lengthening, and aids in endochondral ossification, the process of turning cartilage into bone.
In adipose tissue, thyroid hormone promotes lipolysis, the breakdown of triglycerides into fatty acids and glycerol. The released glycerol can then be used by the liver for gluconeogenesis. In muscles, it regulates protein metabolism by balancing anabolism and catabolism. However, in hyperthyroidism, catabolism predominates, leading to muscle weakness and atrophy.
Due to increased metabolic rate and heat production, thyroid hormone causes vasodilation in the skin, increasing blood flow which results in a flushed appearance and radiates heat. It also enhances sweat production through eccrine and apocrine glands, aiding in evaporative cooling. In the GI tract, thyroid hormone stimulates glandular secretions and increases smooth muscle motility, facilitating normal digestion. Excessive thyroid hormone can lead to increased GI motility and secretions, often resulting in diarrhea, while insufficient hormone can cause constipation.