Iodothyronine deiodinase structure and function: from ascidians to humans

Abstract

Iodothyronine deiodinases are important mediators of thyroid hormone (TH) action. They are present in tissues throughout the body where they catalyse 3,5,3 0 -triiodothyronine (T 3 ) production and degradation via, respectively, outer and inner ring deiodination. Three different types of iodothyronine deiodinases (D1, D2 and D3) have been identified in vertebrates from fish to mammals. They share several common characteristics, including a selenocysteine residue in their catalytic centre, but show also some type-specific differences. These specific characteristics seem very well conserved for D2 and D3, while D1 shows more evolutionary diversity related to its Km, 6-n-propyl-2-thiouracil sensitivity and dependence on dithiothreitol as a cofactor in vitro. The three deiodinase types have an impact on systemic T 3 levels and they all contribute directly or indirectly to intracellular T 3 availability in different tissues. The relative contribution of each of them, however, varies amongst species, developmental stages and tissues. This is especially true for amphibians, where the impact of D1 may be minimal. D2 and D3 expression and activity respond to thyroid status in an opposite and conserved way, while the response of D1 is variable, especially in fish. Recently, a number of deiodinases have been cloned from lower chordates. Both urochordates and cephalochordates possess selenodeiodinases, although they cannot be classified in one of the three vertebrate types. In addition, the cephalochordate amphioxus also expresses a non-selenodeiodinase. Finally, deiodinase-like sequences have been identified in the genome of non-deuterostome organisms, suggesting that deiodination of externally derived THs may even be functionally relevant in a wide variety of invertebrates.

Zebrafish as a Model for Monocarboxyl Transporter 8-Deficiency

“…TSH is secreted by the pituitary and regulates the function of the thyroid gland. TSH consists of ␣-and ␤-subunits (39,40). As the localization of the deiodinase genes had not been previously described in zebrafish, the spatial expression of the three deiodinases was monitored using whole mount ISH (Fig.…”

Plasma thyroid hormones and corticosterone levels in blood of chicken embryos and post hatch chickens exposed during incubation to 1800 MHz electromagnetic field

“…One of the factors that may reduce blood T 4 and T 3 concentrations in the embryos exposed to 1800 MHz electromagnetic fields is the negative impact of RM-EMF on iodine uptake by the thyroid gland [15], which may decrease the synthesis and secretion of T 4 by thyrocytes, followed by T 3 , the main source of which in avian blood peripheral deiodination of T 4 is catalyzed by D1 and D2 deiodinases [23,24]. It is known that one of the main indicators of stress reactions in chickens is an increase in their blood corticosterone levels [25][26][27].…”

Iodothyronine Deiodinases: Key Enzymes Behind the Action of Thyroid Hormone

“…Although metamorphosis of amphibian tadpoles is initiated and maintained obligatorily by T 3 , different tissues such as limb, tail, intestine and gill respond to the same concentration of plasma thyroid hormones at different timing. This seems enabled in part by the fact that different tissues express D2 and D3 at different timing, thereby increasing and decreasing intracellular T 3 concentrations of specific cells largely independent of plasma thyroid hormone concentrations (Becker et al, 1997;Brown and Cai, 2007;Darras and Van Herck, 2012).…”