Department of Pharmacology, University of Athens, 75 Mikras Asias Ave., Goudi, 11527, Athens, Greece.
Laboratory of Organ Regeneration, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Stezzano 87, 24126, Bergamo, Italy.
J Mol Evol. 2020 Jan;88(1):88-103. doi: 10.1007/s00239-019-09908-1. Epub 2019 Aug 27.
Thyroid hormone (TH) signalling is a key modulator of fundamental biological processes that has been evolutionarily conserved in both vertebrate and invertebrate species. TH may have initially emerged as a nutrient signal to convey environmental information to organisms to induce morpho-anatomical changes that could maximise the exploitation of environmental resources, and eventually integrated into the machinery of gene regulation and energy production to become a key regulator of development and metabolism. As such, TH signalling is particularly sensitive to environmental stimuli, and its alterations result in fundamental changes in homeostasis and physiology. Stressful stimuli of various origins lead to changes in the TH-TH receptor (TR) axis in different adult mammalian organs that are associated with phenotypical changes in terminally differentiated cells, the reactivation of foetal development programmes, structural remodelling and pathological growth. Here, we discuss the evolution of TH signalling, review evolutionarily conserved functions of THs in essential biological processes, such as metamorphosis and perinatal development, and analyse the role of TH signalling in the phenotypical and morphological changes that occur after injury, repair and regeneration in adult mammalian organs. Finally, we examine the potential of TH treatment as a therapeutic strategy for improving organ structure and functions following injury.
甲状腺激素（TH）信号是调节基本生物过程的关键调节剂，在脊椎动物和无脊椎动物中都得到了进化上的保守。TH 最初可能作为一种营养信号出现，将环境信息传递给生物体，诱导形态解剖学变化，从而最大限度地利用环境资源，最终整合到基因调控和能量产生的机制中，成为发育和代谢的关键调节剂。因此，TH 信号对环境刺激特别敏感，其改变会导致内稳态和生理学的根本变化。各种来源的应激刺激会导致不同成年哺乳动物器官中 TH-TH 受体（TR）轴的改变，与终末分化细胞的表型变化、胎儿发育程序的重新激活、结构重塑和病理性生长有关。在这里，我们讨论了 TH 信号的进化，回顾了 TH 在变态和围产期发育等基本生物过程中的进化保守功能，并分析了 TH 信号在成年哺乳动物器官损伤、修复和再生后发生的表型和形态变化中的作用。最后，我们探讨了 TH 治疗作为改善损伤后器官结构和功能的治疗策略的潜力。
