Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada.
Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada.
Mol Cell Endocrinol. 2017 Dec 25;459:28-42. doi: 10.1016/j.mce.2017.06.015. Epub 2017 Jun 16.
As one of the most basal living vertebrates, lampreys represent an excellent model system to study the evolution of thyroid hormone (TH) signaling. The lamprey hypothalamic-pituitary-thyroid and reproductive axes overlap functionally. Lampreys have 3 gonadotropin-releasing hormones and a single glycoprotein hormone from the hypothalamus and pituitary, respectively, that regulate both the reproductive and thyroid axes. TH synthesis in larval lampreys takes place in an endostyle that transforms into typical vertebrate thyroid tissue during metamorphosis; both the endostyle and follicular tissue have all the typical TH synthetic components found in other vertebrates. Furthermore, lampreys also have the vertebrate suite of peripheral regulators including TH distributor proteins (THDPs), deiodinases and TH receptors (TRs). Although at the molecular level the components of the lamprey thyroid system are ancestral to other vertebrates, their functions have been largely conserved. TH signaling as it relates to lamprey metamorphosis represents a particularly interesting phenomenon. Unlike other metamorphosing vertebrates, lamprey THs increase throughout the larval period, peak prior to metamorphosis and decline rapidly at the onset of metamorphosis; patterns of deiodinase activity are consistent with these increases and declines. Moreover, goitrogens (which suppress TH levels) initiate precocious metamorphosis, and exogenous TH treatment blocks goitrogen-induced metamorphosis and disrupts natural metamorphosis. Despite this clear physiological difference, TH action via TRs is consistent with higher vertebrates. Based on observations that TRs are upregulated in a tissue-specific fashion during morphogenesis and the finding that lamprey TRs upregulate genes via THs in a fashion similar to higher vertebrates, we propose the following hypothesis for further testing. THs have a dual role in lampreys where high TH levels promote larval feeding and growth and then at the onset of metamorphosis TH levels decrease rapidly; at this time the relatively low TH levels function via TRs in a fashion similar to that of other metamorphosing vertebrates.
作为最基础的活体脊椎动物之一，七鳃鳗是研究甲状腺激素（TH）信号转导进化的极佳模型系统。七鳃鳗的下丘脑-垂体-甲状腺和生殖轴在功能上重叠。七鳃鳗的下丘脑和垂体分别分泌 3 种促性腺激素释放激素和 1 种糖蛋白激素，分别调节生殖轴和甲状腺轴。幼体七鳃鳗的 TH 合成发生在咽上，在变态过程中转化为典型的脊椎动物甲状腺组织；咽上和滤泡组织都具有其他脊椎动物中发现的所有典型的 TH 合成成分。此外，七鳃鳗还具有包括 TH 分布蛋白（THDP）、脱碘酶和 TH 受体（TR）在内的脊椎动物外周调节剂。虽然在分子水平上，七鳃鳗甲状腺系统的组成部分是其他脊椎动物的祖先，但它们的功能在很大程度上是保守的。与七鳃鳗变态相关的 TH 信号转导是一个特别有趣的现象。与其他变态的脊椎动物不同，七鳃鳗的 TH 在整个幼体期内增加，在变态前达到峰值，在变态开始时迅速下降；脱碘酶活性的模式与这些增加和下降一致。此外，甲状腺肿（抑制 TH 水平）引发早熟变态，外源性 TH 处理可阻止甲状腺肿引起的变态，并破坏自然变态。尽管存在这种明显的生理差异，但 TH 通过 TR 的作用与高等脊椎动物一致。基于观察到 TR 在形态发生过程中以组织特异性方式上调，以及发现七鳃鳗 TR 通过 TH 上调基因的方式与高等脊椎动物相似，我们提出以下假设进行进一步测试。TH 在七鳃鳗中具有双重作用，高 TH 水平促进幼体的摄食和生长，然后在变态开始时 TH 水平迅速下降；此时相对较低的 TH 水平通过 TR 以类似于其他变态脊椎动物的方式发挥作用。
