Unité Mixte de Recherche 7221, Département Adaptation du Vivant, Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, Alliance Sorbonne Universités, 75231 Paris, France.
Section on Molecular Morphogenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Endocrinology. 2024 Sep 26;165(11). doi: 10.1210/endocr/bqae137.
Thyroid hormones and their receptors (TRs) play critical roles during vertebrate development. One of the most dramatic developmental processes regulated by thyroid hormones is frog metamorphosis, which mimics the postembryonic (perinatal) period in mammals. Here, we review some of the findings on the developmental functions of thyroid hormones and TRs as well as their associated mechanisms of action obtained from this model system. More than 2 decades ago, a dual function model was proposed for TR in anuran development. During larval development, unliganded receptors recruit corepressors to repress thyroid hormone response genes to prevent premature metamorphic changes. Subsequently, when thyroid hormone levels rise, liganded receptors recruit coactivators to activate thyroid hormone response genes, leading to metamorphic changes. Over the years, molecular and genetic approaches have provided strong support for this model and have shown that it is applicable to mammalian development as well as to understanding the diverse effects of thyroid hormones in normal physiology and diseases caused by thyroid hormone signaling dysfunction.
甲状腺激素及其受体 (TR) 在脊椎动物发育过程中发挥着关键作用。甲状腺激素调控的最显著的发育过程之一是青蛙变态，这模拟了哺乳动物的胚胎后（围产期）阶段。在这里，我们回顾了从该模型系统获得的甲状腺激素和 TR 的发育功能及其相关作用机制的一些发现。20 多年前，人们提出了一个双功能模型来解释 TR 在无尾两栖动物发育中的作用。在幼虫发育过程中，未结合配体的受体募集核心抑制剂来抑制甲状腺激素反应基因，以防止过早的变态变化。随后，当甲状腺激素水平上升时，结合配体的受体募集共激活剂来激活甲状腺激素反应基因，导致变态。多年来，分子和遗传方法为该模型提供了强有力的支持，并表明它不仅适用于哺乳动物的发育，也适用于理解甲状腺激素在正常生理和甲状腺激素信号功能障碍引起的疾病中的多种作用。
