Thyroxine

Thyroxine, also known as T₄, is a hormone produced by the thyroid gland. It is the primary form of thyroid hormone found in the blood and acts as a prohormone of the more active thyroid hormone, triiodothyronine (T₃).<ref name="Li_2020">Template:Cite journal</ref> Thyroxine and its active metabolites are essential for regulating metabolic rate, supporting heart and muscle function, promoting brain development, and maintaining bone health.<ref name="Kim_2013">Template:Cite journal</ref><ref name="Mullur_2014">Template:Cite journal</ref>

Regulation

Thyroxine has a half-life of approximately one week and hence maintains relatively stable blood levels. Its production and release are controlled through a complex feedback loop involving the hypothalamus, pituitary gland, and thyroid gland. This regulatory system ensures that optimal hormone levels are maintained.<ref name = "Rousset_2015">Template:Cite book</ref>

Biosynthesis

File:Thyroxine biosynthesis.svg

Biosynthesis of thyroxine<ref name = "Rousset_2015" />

Thyroxine biosynthesis is a multi-step process that occurs in follicular cell within the thyroid gland. The synthesis of thyroxine requires adequate iodine supply and appropriate hormonal control.<ref name="Sorrenti_2021">Template:Cite journal</ref><ref name = "Shahid_2023">Template:Cite book</ref><ref name = "Rousset_2015" />

The process begins with the active uptake of iodide from the bloodstream by thyroid follicular cells through the sodium/iodide symporter (NIS) located in the basolateral membrane. Once inside the cell, iodide is transported to the follicular lumen, where it undergoes oxidation by the enzyme thyroid peroxidase (TPO) in the presence of hydrogen peroxide generated by the NADPH oxidase DUOX2.<ref name = "Shahid_2023" /> The oxidized iodine then iodinates tyrosyl residues of thyroglobulin (Tg), a glycoprotein synthesized by thyroid cells and stored in the follicular lumen.<ref name="Sorrenti_2021" /> This process, known as organification, results in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT) residues within the Tg molecule.<ref name = "Shahid_2023" /><ref name = "Rousset_2015" />

The final step in thyroxine synthesis involves the free radical mediated coupling of two DIT residues, catalyzed by TPO, to form T₄ while still attached to the Tg backbone.<ref name="Sorrenti_2021" /><ref name = "Shahid_2023" /> When thyroid hormone is needed, Tg is internalized by thyrocytes, and proteolytic enzymes in lysosomes cleave the T₄ from Tg, allowing for its release into the bloodstream.<ref name = "Rousset_2015" /> This intricate biosynthetic pathway is tightly regulated by thyroid-stimulating hormone (TSH) from the pituitary gland, which influences virtually every stage of thyroid hormone production.<ref name = "Rousset_2015" />