Bianco Antonio C, da Conceição Rodrigo R
Division of Endocrinology, Diabetes and Metabolism, Rush University Medical Center, Chicago, IL, USA.
Programa de Pos-Graduacao em Medicina, Endocrinologia Clinica, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil.
Methods Mol Biol. 2018;1801:67-83. doi: 10.1007/978-1-4939-7902-8_8.
Thyroid hormone signaling is customized in a time and cell-specific manner by the deiodinases, homodimeric thioredoxin fold containing selenoproteins. This ensures adequate T3 action in developing tissues, healthy adults and many disease states. D2 activates thyroid hormone by converting the pro-hormone T4 to T3, the biologically active thyroid hormone. D2 expression is tightly regulated by transcriptional mechanisms triggered by endogenous as well as environmental cues. There is also an on/off switch mechanism that controls D2 activity that is triggered by catalysis and functions via D2 ubiquitination/deubiquitination. D3 terminates thyroid hormone action by inactivation of both T4 and T3 molecules. Deiodinases play a role in thyroid hormone homeostasis, development, growth and metabolic control by affecting the intracellular levels of T3 and thus gene expression on a cell-specific basis. In many cases, tight control of these pathways by T3 is achieved with coordinated reciprocal changes in D2-mediated thyroid hormone activation D3-mediated thyroid hormone inactivation.
脱碘酶以时间和细胞特异性方式定制甲状腺激素信号传导，脱碘酶是含硒蛋白的同二聚体硫氧还蛋白折叠体。这确保了在发育中的组织、健康成年人以及许多疾病状态下甲状腺激素具有足够的作用。D2通过将前体激素T4转化为生物活性甲状腺激素T3来激活甲状腺激素。D2的表达受到内源性以及环境信号触发的转录机制的严格调控。还存在一种开/关开关机制，该机制通过催化触发并通过D2泛素化/去泛素化发挥作用来控制D2活性。D3通过使T4和T3分子失活来终止甲状腺激素的作用。脱碘酶通过影响细胞内T3水平并因此在细胞特异性基础上影响基因表达，在甲状腺激素稳态、发育、生长和代谢控制中发挥作用。在许多情况下，通过D2介导的甲状腺激素激活与D3介导的甲状腺激素失活的协调相互变化，实现了T3对这些途径的严格控制。
