Notes on the History of Cellular Uptake and Deiodination of Thyroid Hormone

Abstract

In this mini review on the history of the research devoted to thyroid hormone metabolism two pathways are discussed, i.e. uptake and subsequent deiodination in cells and tissues. In the 1950's the investigations of these processes were greatly stimulated when 131I became available for research purposes. The true nature of both mechanisms surfaced in the 1970's when it became apparent that transport of thyroid hormones into cells was a regulated carrier mediated process, while deiodination appeared to be catalyzed by different types of enzymes. Kinetic data indicated that these processes were of great importance in the ultimate regulation of thyroid hormone bio-availability.

TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

“…Additional mechanisms of homeostasis include autoregulation, where clearance of iodothyronines increases with their plasma levels [64–66], increased degradation of TSH in hyperthyroidism [67], possible ultrashort feedback control of TRH secretion, [68] and numerous mechanisms involving control of thyroid hormone transporters and receptor density [15, 17, 69–73]. Moreover, iodothyronines are subject to enterohepatic circulation that is a target of additional control signals [16, 74] and due to the prokinetic effects of iodothyronines possibly including thyroid hormones themselves [75, 76].…”

New insights into the role of thyroid hormone in cardiac remodeling: time to reconsider?

“…Passage of T4 may be passive, given the lipophilic nature or transporter-and energy-dependent [12]. T4 is converted to triiodothyronine (T3) by de-iodinases which are selenoproteins (type-1 and type-2 de-iodinases, D1 and D2), while T3 is degraded by type-3 de-iodinase, D3 [13].…”

Thyroid Hormones and Thyromimetics

“…Cellular passage of thyroid hormones was long thought to be passive, considering their hydrophobic nature. It is now evident that thyroid hormone uptake is both transporter and energy dependent [227] and also that intracellular thyroid An OATP family member, OATPC1, displays high affinity and allows both import and efflux for L-T 4 , but not for L-T 3 [229], which suggests that OATPC1 may be an important transporter of L-T 4 across the blood-brain barrier (BBB). As mentioned above in Section 2.4.3, MCT8 is another transporter with high affinity for L-T 4 and L-T 3 in rodents [230], while the human version is more specific for L-T 3 .…”