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首页> 外文期刊>Molecular and Cellular Biology >Both thyroid hormone and 9-cis retinoic acid receptors are required to efficiently mediate the effects of thyroid hormone on embryonic development and specific gene regulation in Xenopus laevis.
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Both thyroid hormone and 9-cis retinoic acid receptors are required to efficiently mediate the effects of thyroid hormone on embryonic development and specific gene regulation in Xenopus laevis.

机译：甲状腺激素和9-顺式视黄酸受体都需要有效介导甲状腺激素对非洲爪蟾胚胎发育和特定基因调控的影响。

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Tissue culture transfection and in vitro biochemical studies have suggested that heterodimers of thyroid hormone receptors (TRs) and 9-cis retinoic acid receptors (RXRs) are the likely in vivo complexes that mediate the biological effects of thyroid hormone, 3,5,3'-triiodothyronine (T3). However, direct in vivo evidence for such a hypothesis has been lacking. We have previously reported a close correlation between the coordinated expression of TR and RXR genes and tissue-dependent temporal regulation of organ transformations during Xenopus laevis metamorphosis. By introducing TRs and RXRs either individually or together into developing Xenopus embryos, we demonstrate here that RXRs are critical for the developmental function of TRs. Precocious expression of TRs and RXRs together but not individually leads to drastic, distinct embryonic abnormalities, depending upon the presence or absence of T3, and these developmental effects require the same receptor domains as those required for transcriptional regulation by TR-RXR heterodimers. More importantly, the overexpressed TR-RXR heterodimers faithfully regulate endogenous T3 response genes that are normally regulated by T3 only during metamorphosis. That is, they repress the genes in the absence of T3 and activate them in the presence of the hormone. On the other hand, the receptors have no effect on a retinoic acid (RA) response gene. Thus, RA- and T3 receptor-mediated teratogenic effects in Xenopus embryos occur through distinct molecular pathways, even though the resulting phenotypes have similarities.
机译：组织培养转染和体外生化研究表明，甲状腺激素受体（TRs）和9-顺式视黄酸受体（RXRs）的异二聚体可能是体内复合物，介导甲状腺激素的生物学作用3,5,3' -三碘甲状腺素（T3）。但是，缺乏关于这种假设的直接体内证据。我们先前已报道非洲爪蟾变态期间TR和RXR基因的协调表达与器官转化的组织依赖性时间调控之间存在密切的相关性。通过将TRs和RXRs单独或一起引入发育中的非洲爪蟾胚胎，我们在这里证明RXRs对TRs的发育功能至关重要。 TRs和RXRs的过早表达，但不是单独导致严重，明显的胚胎异常，这取决于T3的存在与否，并且这些发育效应需要与TR-RXR异源二聚体转录调控所需的受体结构域相同的受体结构域。更重要的是，过表达的TR-RXR异二聚体忠实地调节内源性T3响应基因，该基因通常仅在变态期间才受T3调控。也就是说，它们在不存在T3的情况下抑制基因，而在存在激素的情况下激活它们。另一方面，受体对视黄酸（RA）反应基因没有影响。因此，非洲爪蟾和T3受体介导的致畸作用通过不同的分子途径发生，即使所得表型具有相似性。

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