Murata Y
Department of Teratology and Genetics, Nagoya University, Japan.
Nagoya J Med Sci. 1998 Oct;61(3-4):103-15.
Thyroid hormone is essential for normal development and maintaining metabolic homeostasis. In mediating the thyroid hormone action, the thyroid hormone receptor (TR) plays a key role. Almost one decade ago, the cloning of TR was achieved, revealing the existence of at least two genes, TR alpha and TR beta, which encode TR. From these genes several TR isoforms can be generated by alternative splicing. They are designated as TR alpha 1, TR alpha 2 (inactive form), TR beta 1 and TR beta 2. Since the discovery of these TR isoforms, many studies have attempted to demonstrate their relative contribution to mediate thyroid hormone in various tissues. The distinct tissue distribution and the ontogenic expression of the TR isoforms, and the fact that TR gene abnormalities associated with the syndrome of resistance to thyroid hormone (RTH) have been found only in the TR beta gene, indicate that products of TR alpha and TR beta have distinct roles. However, no direct evidence of the distinct roles of the TR isoforms has been shown. Gene knockouts of either TR isoform would provide important information to understanding their specific roles. In this review, the history of the TR isoform discovery and studies attempting to demonstrate the specific roles of TR isoforms are summarized, and recent reports dealing with knockouts of TR isoforms are comprehensively presented.
甲状腺激素对于正常发育和维持代谢稳态至关重要。在介导甲状腺激素作用过程中，甲状腺激素受体（TR）发挥着关键作用。大约十年前，TR被克隆出来，揭示了至少存在两个编码TR的基因，即TRα和TRβ。通过可变剪接，从这些基因可产生几种TR亚型。它们被命名为TRα1、TRα2（无活性形式）、TRβ1和TRβ2。自从发现这些TR亚型以来，许多研究试图证明它们在各种组织中介导甲状腺激素的相对作用。TR亚型独特的组织分布和个体发育表达，以及仅在TRβ基因中发现与甲状腺激素抵抗综合征（RTH）相关的TR基因异常这一事实，表明TRα和TRβ的产物具有不同的作用。然而，尚未有直接证据表明TR亚型具有不同的作用。任一TR亚型的基因敲除将为理解它们的特定作用提供重要信息。在这篇综述中，总结了TR亚型发现的历史以及试图证明TR亚型特定作用的研究，并全面介绍了有关TR亚型基因敲除的最新报道。
