Manzon Lori A, Youson John H, Holzer Guillaume, Staiano Leopoldo, Laudet Vincent, Manzon Richard G
Department of Zoology and Division of Life Sciences, University of Toronto, Toronto, ON M1A 1C4, Canada.
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, École Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Gen Comp Endocrinol. 2014 Aug 1;204:211-22. doi: 10.1016/j.ygcen.2014.05.030. Epub 2014 Jun 4.
Sea lampreys (Petromyzon marinus) are members of the ancient class Agnatha and undergo a metamorphosis that transforms blind, sedentary, filter-feeding larvae into free-swimming, parasitic juveniles. Thyroid hormones (THs) appear to be important for lamprey metamorphosis, however, serum TH concentrations are elevated in the larval phase, decline rapidly during early metamorphosis and remain low until metamorphosis is complete; these TH fluctuations are contrary to those of other metamorphosing vertebrates. Moreover, thyroid hormone synthesis inhibitors (goitrogens) induce precocious metamorphosis and exogenous TH treatments disrupt natural metamorphosis in P. marinus. Given that THs exert their effects by binding to TH nuclear receptors (TRs) that often act as heterodimers with retinoid X receptors (RXRs), we cloned and characterized these receptors from P. marinus and examined their expression during metamorphosis. Two TRs (PmTR1 and PmTR2) and three RXRs (PmRXRs) were isolated from P. marinus cDNA. Phylogenetic analyses group the PmTRs together on a branch prior to the gnathostome TRα/β split. The three RXRs also group together, but our data indicated that these transcripts are most likely either allelic variants of the same gene locus, or the products of a lamprey-specific duplication event. Importantly, these P. marinus receptors more closely resemble vertebrate as opposed to invertebrate chordate receptors. Functional analysis revealed that PmTR1 and PmTR2 can activate transcription of TH-responsive genes when treated with nanomolar concentrations of TH and they have distinct pharmacological profiles reminiscent of vertebrate TRβ and TRα, respectively. Also similar to other metamorphosing vertebrates, expression patterns of the PmTRs during lamprey metamorphosis suggest that PmTR1 has a dynamic, tissue-specific expression pattern that correlates with tissue morphogenesis and biochemical changes and PmTR2 has a more uniform expression pattern. This TR expression data suggests that THs, either directly or via a metabolite, may function to positively modulate changes at the tissue or organ levels during lamprey metamorphosis. Collectively the results presented herein support the hypothesis that THs have a dual functional role in the lamprey life cycle whereby high levels promote larval feeding, growth and lipogenesis and low levels promote metamorphosis.
海七鳃鳗（Petromyzon marinus）是古老的无颌纲成员，会经历变态发育，将盲眼、固着、滤食性的幼体转变为自由游动的寄生性幼体。甲状腺激素（THs）似乎对七鳃鳗的变态发育很重要，然而，血清TH浓度在幼体阶段升高，在变态发育早期迅速下降，并在变态发育完成前一直保持在低水平；这些TH波动与其他变态发育的脊椎动物相反。此外，甲状腺激素合成抑制剂（致甲状腺肿物质）会诱导早熟变态，而外源性TH处理会破坏海七鳃鳗的自然变态。鉴于THs通过与甲状腺激素核受体（TRs）结合发挥作用，而TRs通常与视黄酸X受体（RXRs）形成异二聚体，我们从海七鳃鳗中克隆并鉴定了这些受体，并研究了它们在变态发育过程中的表达。从海七鳃鳗cDNA中分离出两个TRs（PmTR1和PmTR2）和三个RXRs（PmRXRs）。系统发育分析将PmTRs聚集在一个分支上，位于有颌类动物TRα/β分裂之前。三个RXRs也聚集在一起，但我们的数据表明，这些转录本很可能是同一基因座的等位基因变体，或者是七鳃鳗特有的复制事件的产物。重要的是，这些海七鳃鳗受体与脊椎动物受体更为相似，而非无脊椎脊索动物受体。功能分析表明，当用纳摩尔浓度的TH处理时，PmTR1和PmTR2可以激活TH反应基因的转录，并且它们具有独特的药理学特征，分别让人联想到脊椎动物的TRβ和TRα。同样与其他变态发育的脊椎动物相似，七鳃鳗变态发育过程中PmTRs的表达模式表明，PmTR1具有动态的、组织特异性的表达模式，与组织形态发生和生化变化相关，而PmTR2具有更均匀的表达模式。这种TR表达数据表明，THs可能直接或通过一种代谢产物，在七鳃鳗变态发育过程中对组织或器官水平的变化起正向调节作用。本文呈现的结果共同支持了这样一种假设，即THs在七鳃鳗生命周期中具有双重功能作用，高水平促进幼体摄食、生长和脂肪生成，低水平促进变态发育。
