Laboratory of Comparative Endocrinology, Biology Department, KU Leuven, Leuven, Belgium.
Endocrinology. 2021 Jun 1;162(6). doi: 10.1210/endocr/bqab039.
Iodothyronine deiodinases are enzymes capable of activating and inactivating thyroid hormones (THs) and have an important role in regulating TH action in tissues throughout the body. Three types of deiodinases (D1, D2, and D3) were originally defined based on their biochemical characteristics. Cloning of the first complementary DNAs in the 1990s (Dio1 in rat and dio2 and dio3 in frog) allowed to confirm the existence of 3 distinct enzymes. Over the years, increasing genomic information revealed that deiodinases are present in all chordates, vertebrates, and nonvertebrates and that they can even be found in some mollusks and annelids, pointing to an ancient origin. Research in nonmammalian models has substantially broadened our understanding of deiodinases. In relation to their structure, we discovered for instance that biochemical properties such as inhibition by 6-propyl-2-thiouracil, stimulation by dithiothreitol, and temperature optimum are subject to variation. Data from fish, amphibians, and birds were key in shifting our view on the relative importance of activating and inactivating deiodination pathways and in showing the impact of D2 and D3 not only in local but also whole body T3 availability. They also led to the discovery of new local functions such as the acute reciprocal changes in D2 and D3 in hypothalamic tanycytes upon photostimulation, involved in seasonal rhythmicity. With the present possibilities for rapid and precise gene silencing in any species of interest, comparative research will certainly further contribute to a better understanding of the importance of deiodinases for adequate TH action, also in humans.
碘甲状腺原氨酸脱碘酶是能够激活和失活甲状腺激素 (THs) 的酶，在调节全身组织中 TH 作用方面具有重要作用。最初根据其生化特性定义了三种脱碘酶 (D1、D2 和 D3)。20 世纪 90 年代克隆的第一个 cDNA（大鼠的 Dio1 和青蛙的 dio2 和 dio3）证实了 3 种不同酶的存在。多年来，不断增加的基因组信息表明脱碘酶存在于所有脊索动物、脊椎动物和无脊椎动物中，甚至在一些软体动物和环节动物中也存在，这表明其起源古老。非哺乳动物模型的研究大大拓宽了我们对脱碘酶的理解。在与它们的结构相关的研究中，我们发现，例如，生化特性（如被 6-丙基-2-硫尿嘧啶抑制、被二硫苏糖醇刺激和最适温度）会发生变化。来自鱼类、两栖动物和鸟类的数据改变了我们对激活和失活脱碘途径相对重要性的看法，并表明 D2 和 D3 的影响不仅存在于局部，还存在于全身 T3 的可用性。它们还导致了新的局部功能的发现，例如光刺激下下丘脑的成神经细胞中 D2 和 D3 的急性相互变化，参与季节性节律。由于目前在任何感兴趣的物种中都可以快速和精确地进行基因沉默，因此比较研究肯定会进一步有助于更好地理解脱碘酶对适当 TH 作用的重要性，包括在人类中。
