Chapter 6 - Thyroid-Stimulating Hormone

Abstract

Thyroid-stimulating hormone (TSH) is a glycoprotein produced by the thyrotroph cells in the anterior pituitary and is pivotal for thyroid gland development and thyroid hormone production. Precise temporal regulation is required for proper thyrotroph cell development and function. Mutations in genes critical to thyrotroph ontogeny are found in patients with aberrant TSH production. TSH consists of two noncovalently linked subunits, α and β, that are encoded by two separate genes on different chromosomes. The β-subunit is specific for TSH, while the α-subunit is common to all glycoproteins hormones. Thyroid hormone and thyrotrophin-releasing hormone (TRH) are the most important regulators of TSH biosynthesis and secretion, although a plethora of hormones, substances, and drugs have been described to be of influence as well. Production of bioactive TSH, mainly in response to TRH stimulation, involves a process of cotranslational glycosylation and folding that enables combination between the nascent α- and β-subunits. TSH is stored in secretory granules and released into the circulation in a regulated manner, displaying a dual and diurnal pattern. Circulating TSH binds to specific cell-surface receptors on the thyroid gland where it stimulates the production of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). T4 is primarily a prohormone that is metabolized peripherally to T3, which acts, mainly through genomic action, on multiple organs and tissues to modulate many metabolic processes as well as result in negative inhibition of TSH output. The introduction of sensitive TSH assays has allowed accurate measurement of the concentration of circulating TSH and has led to recognition of abnormal TSH production related to abnormal hypothalamic–pituitary–thyroid axis functions.