11th April 2024

Physiology of the thyroid hormones

Thyroid hormones have a wide range of effects across multiple organs and tissues in the body. Production of thyroid hormones starts with the release of thyrotropin-releasing hormone from the periventricular nucleus of the hypothalamus. TRH binds to G-protein coupled receptors in cells located in the anterior pituitary gland, activating a complex signalling cascade that ends with the activation of protein kinase C, which stimulates thyroid-stimulating hormone production. TSH is released into the blood, where it will bind to G-protein coupled receptors of thyroid follicular cells, initiating the production of thyroglobulins. It also activates protein kinase A, an important enzyme responsible for mediating iodide uptake and oxidation in thyroglobulins via NaI symporters and thyroid peroxidase, respectively. Coupling reactions occur between MIT and DIT, producing T3 and T4, which are released into the circulation in a 20:80 ratio.

Only a small proportion of thyroid hormone remains unbound (~0.2%). The rest react to and are carried by transporter proteins such as thyroxine-binding globulin and albumin. When required, T3/T4 dissociate themselves from their transporter protein and enter the targeted cells either by diffusion or surface carrier proteins. Like most hormones associated with hypothalamus-pituitary axis, the concentration of thyroid hormones is controlled by a negative feedback loop. High concentrations of T3/T4 inhibit the release of TRH and TSH. External influences can affect this system; hormones such as somatostatin and glucocorticoids can inhibit TSH production, while environmental factors such as stress and exercise can increase TRH release.