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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Thyroid hormone receptor α is a molecular switch of cardiac function between fetal and postnatal life
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Thyroid hormone receptor α is a molecular switch of cardiac function between fetal and postnatal life

机译：甲状腺激素受体α是胎儿和产后心脏功能的分子转换

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摘要

Thyroid hormones are involved in the regulation of many physiological processes and regulate gene transcription by binding to their nuclear receptors TRα and TRβ. In the absence of triiodothy-ronine (T3), the unliganded receptors (aporeceptors) do bind DNA and repress the transcription of target genes. The role of thyroid hormone aporeceptors as repressors was observed in hypothyroid adult mice, but its physiological relevance in nonpathological hypothyroid conditions remained to be determined. Here we show that, in the normal mouse fetus, TRα aporeceptors repress heart rate as well as the expression of TRβ and several genes encoding ion channels involved in cardiac contractile activity. Right after birth, when T3 concentration sharply increases, liganded TRα (holoreceptors) turn on the expression of some of these same genes concomitantly with heart rate increase. These data describe a physiological situation under which conversion of TRα from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process.
机译：甲状腺激素参与许多生理过程的调节，并通过与它们的核受体TRα和TRβ结合来调节基因转录。在没有三碘甲腺嘌呤（T3）的情况下，未配体的受体（无感受器）会结合DNA并抑制靶基因的转录。在甲状腺功能减退的成年小鼠中观察到了甲状腺激素失调受体作为阻遏物的作用，但其在非病理性甲状腺功能减退情况下的生理相关性仍有待确定。在这里，我们表明，在正常的小鼠胎儿中，TRα感受器抑制心率以及TRβ的表达和编码参与心脏收缩活动的离子通道的几种基因。出生后不久，当T3浓度急剧增加时，配体TRα（全受体）就会随着心率的增加而开启某些相同基因的表达。这些数据描述了一种生理情况，在这种情况下，随着T3可用性的变化，TRα从脱辅基受体转变为全受体，在发育过程中起决定性作用。

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