TRα2——未调好的第二小提琴还是微调甲状腺激素作用？

Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.

Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.

Int J Mol Sci. 2022 Jun 23;23(13):6998. doi: 10.3390/ijms23136998.

Thyroid hormones (THs) control a wide range of physiological functions essential for metabolism, growth, and differentiation. On a molecular level, TH action is exerted by nuclear receptors (TRs), which function as ligand-dependent transcription factors. Among several TR isoforms, the function of TRα2 remains poorly understood as it is a splice variant of TRα with an altered C-terminus that is unable to bind T3. This review highlights the molecular characteristics of TRα2, proposed mechanisms that regulate alternative splicing and indications pointing towards an antagonistic function of this TR isoform in vitro and in vivo. Moreover, remaining knowledge gaps and major challenges that complicate TRα2 characterization, as well as future strategies to fully uncover its physiological relevance, are discussed.

甲状腺激素（THs）控制着广泛的生理功能，这些功能对新陈代谢、生长和分化至关重要。在分子水平上，TH 的作用是通过核受体（TRs）发挥的，核受体作为配体依赖性转录因子发挥作用。在几种 TR 同种型中，TRα2 的功能知之甚少，因为它是 TRα 的剪接变体，其 C 末端发生改变，无法结合 T3。本综述强调了 TRα2 的分子特征，提出了调节选择性剪接的机制，并指出了这种 TR 同种型在体外和体内具有拮抗作用的迹象。此外，还讨论了仍存在的知识空白和使 TRα2 特征复杂化的主要挑战，以及充分揭示其生理相关性的未来策略。