Chemical Biology of Thyroid Hormones

Abstract

March 2023 | 137 thyroid gland to make thyroid hormones (THs). Upon reaching an optimum concentration in the blood plasma, the secretion of T4 from the thyroid gland is stopped by a negative feedback mechanism. [3,4] THs regulate different physiological functions of the human body like cardiovascular function, normal growth, and maturation of bones and overall metabolism of fat, protein, and carbohydrate. They also control the body temperature, heart rate and protein synthesis. This general article highlights the basic chemistry associated with THs synthesis, transport, and metabolism (Figure 1). Biosynthesis of thyroid hormonesThe biosynthesis of THs takes place in the colloidal lumen of thyroid follicular cells with the help of thyroglobulin (Tg, a highly crosslinked glycoprotein), thyroid peroxidase (TPO), iodide (I-), and hydrogen peroxide albumin (HSA). T4 then enters the target cells through membrane-associated transporters like monocarboxylate transporter 8 (MCT8),10 (MCT10) and organic anion transporter 1c1 (OATP1C1). Subsequently, T4 undergoes monodeiodination by iodothyronine deiodinase (DIOs) enzymes to produce the active form of thyroid hormone T3, which further binds with the thyroid nuclear receptors and recognizes different thyroid hormone-responsive elements (TREs) of target genes and regulates the gene translation. The secretion of THs by thyroid are controlled by hypothalamus and pituitary. Hypothalamus secretes thyrotropin-releasing hormone (TRH), a tripeptide (pyro glutamyl-histidyl-proline amide), which stimulates the pituitary to synthesize and release the thyroid-stimulating hormone (TSH) which signals the