Morvan-Dubois Ghislaine, Demeneix Barbara A, Sachs Laurent M
Mol Cell Endocrinol. 2008 Oct 10;293(1-2):71-9. doi: 10.1016/j.mce.2008.06.012. Epub 2008 Jun 28.
Amphibian metamorphosis is a well-established model for dissecting the mechanisms underlying thyroid hormone (TH) action. How the pro-hormone, T(4), the active form, T(3), the deiodinases and the nuclear receptors (TRs) contribute to metamorphosis in Xenopus has been extensively investigated. Our recent work has concentrated on two key ideas in TH signalling in Xenopus: first, that there could be active roles for both liganded and unliganded receptors, and second, that ligand availability is a determining factor orchestrating these actions and is tightly controlled in target tissues. Recently, we addressed these questions at stages preceding metamorphosis, i.e. during embryogenesis, before differentiation of a functional thyroid gland. We show that repression by unliganded TR is essential to craniofacial and eye development during early development and that at these stages all three deiodinases are active. These results open new perspectives on the potential roles of TH signalling during embryogenesis.
两栖动物变态是剖析甲状腺激素(TH)作用机制的一个成熟模型。前体激素T4、活性形式T3、脱碘酶和核受体(TRs)如何促成非洲爪蟾的变态已得到广泛研究。我们最近的工作集中在非洲爪蟾TH信号传导的两个关键观点上:第一,结合配体和未结合配体的受体都可能发挥积极作用;第二,配体可用性是协调这些作用的决定性因素,并且在靶组织中受到严格控制。最近,我们在变态前的阶段,即在胚胎发育期间、功能性甲状腺分化之前,解决了这些问题。我们表明,未结合配体的TR的抑制作用对于早期发育过程中的颅面和眼睛发育至关重要,并且在这些阶段所有三种脱碘酶都是活跃的。这些结果为TH信号传导在胚胎发育过程中的潜在作用开辟了新的视角。