Chemistry and Biology in the Biosynthesis and Action of Thyroid Hormones

Abstract

Thyroid hormones (THs) are secreted by the thyroid gland. They control lipid, carbohydrate, and protein metabolism, heart rate, neural development, as well as cardiovascular, renal, and brain functions. The thyroid gland mainly produces l-thyroxine (T4) as a prohormone, and 5'-deiodination of T4 by iodothyronine deiodinases generates the nuclear receptor binding hormone T3. In this Review, we discuss the basic aspects of the chemistry and biology as well as recent advances in the biosynthesis of THs in the thyroid gland, plasma transport, and internalization of THs in their target organs, in addition to the deiodination and various other enzyme-mediated metabolic pathways of THs. We also discuss thyroid hormone receptors and their mechanism of action to regulate gene expression, as well as various thyroid-related disorders and the available treatments.

GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation

“…TH biosynthesis and secretion is controlled by the hypothalamus-pituitary-thyroid axis and is maintained constant via negative feedback regulation (1,2). Thyroidstimulating hormone (TSH), produced by thyrotrophic cells in the pituitary gland, stimulates TH biosynthesis and secretion, while the production of TSH is regulated by the hypothalamic TSHreleasing hormone and modulated by TH via a negative feedback loop.…”

The Remarkable Effect of Halogen Substitution on the Membrane Transport of Fluorescent Molecules in Living Cells

“…It is known that halogen atoms form halogen bonds with electron donors and their halogen bonding ability increases from chlorine to bromine to iodine. [20] Although the thyroid hormones,T4and T3, are known to form halogen bonds with their transport proteins transthyretin (TTR) and thyroxine-binding globulin (TBG), [21] it is not known whether halogen bonding is responsible for the cellular uptake of thyroid hormones by MCT8. [18] Although halogen bonds have attracted significant attention in drug discovery, [19] it remains unclear whether they play key roles beyond their applications in improving drug-target interactions.Matile and co-workers and others showed that halogen bonds can be used for ion transport in synthetic membrane systems.…”

Halogen Bonding in Biomimetic Deiodination of Thyroid Hormones and their Metabolites and Dehalogenation of Halogenated Nucleosides

“…In addition to deiodination, THs undergo a variety of other metabolic pathways, including sulfation, glucuronidation, decarboxylation, and oxidative deamination . These pathways mainly increase the excretion of THs through urine and/or bile.…”