Campo Aurora, Lafont Anne-Gaëlle, Lefranc Benjamin, Leprince Jérôme, Tostivint Hervé, Kamech Nédia, Dufour Sylvie, Rousseau Karine
Muséum National d'Histoire Naturelle, Research Unit BOREA (Biology of Aquatic Organisms and Ecosystems), CNRS 7208, IRD 207, Sorbonne Université, Université de Caen Normandie, Université des Antilles, Paris, France.
Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U1239, Normandy University, Rouen, France.
Front Endocrinol (Lausanne). 2018 Jun 11;9:304. doi: 10.3389/fendo.2018.00304. eCollection 2018.
In mammals, neurokinin B (NKB) is a short peptide encoded by the gene . It is involved in the brain control of reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons, mainly kisspeptin. We investigated genes and peptides in a basal teleost, the European eel, which shows an atypical blockade of the sexual maturation at a prepubertal stage. Two paralogous genes ( and ) were identified in the eel genome, each encoding two peptides (NKBa or b and NKB-related peptide NKB-RPa or b). Amino acid sequence of eel NKBa is identical to human NKB, and the three others are novel peptide sequences. The four eel peptides present the characteristic C-terminal tachykinin sequence, as well as a similar alpha helix 3D structure. genes were identified in 52 species of vertebrates, and a phylogeny analysis was performed on the predicted TAC3 pre-pro-peptide sequences. A synteny analysis was also done to further assess the evolutionary history of genes. Duplicated enes in teleosts likely result from the teleost-specific whole genome duplication (3R). Among teleosts, TAC3b precursor sequences are more divergent than TAC3a, and a loss of gene would have even occurred in some teleost lineages. NKB-RP peptide, encoded beside NKB by gene in actinopterygians and basal sarcopterygians, would have been lost in ancestral amniotes. Tissue distribution of eel and mRNAs showed major expression of both transcripts in the brain especially in the diencephalon, as analyzed by specific qPCRs. Human NKB has been tested on primary culture of eel pituitary cells. Human NKB dose-dependently inhibited the expression of , while having no effect on other glycoprotein hormone subunits (, and ) nor on . Human NKB also dose-dependently inhibited the expression of GnRH receptor (r2). The four eel peptides have been synthesized and also tested . They all inhibited the expression of both and of . This reveals a potential dual inhibitory role of the four peptides encoded by the two genes in eel reproduction, exerted at the pituitary level on both luteinizing hormone and GnRH receptor.
在哺乳动物中，神经激肽B（NKB）是一种由该基因编码的短肽。它通过刺激促性腺激素释放激素（GnRH）神经元，主要是 kisspeptin，参与大脑对生殖的控制。我们研究了一种基底硬骨鱼——欧洲鳗鲡中的相关基因和肽，欧洲鳗鲡在青春期前阶段表现出性成熟的非典型阻滞。在鳗鲡基因组中鉴定出两个旁系同源基因（ 和 ），每个基因编码两种肽（NKBa或b以及NKB相关肽NKB-RPa或b）。鳗鲡NKBa的氨基酸序列与人类NKB相同，其他三种是新的肽序列。这四种鳗鲡肽具有特征性的C末端速激肽序列，以及相似的α螺旋三维结构。在52种脊椎动物中鉴定出了相关基因，并对预测的TAC3前体肽序列进行了系统发育分析。还进行了共线性分析以进一步评估相关基因的进化历史。硬骨鱼中的重复基因可能源于硬骨鱼特有的全基因组复制（3R）。在硬骨鱼中，TAC3b前体序列比TAC3a更具差异性，并且在一些硬骨鱼谱系中甚至可能发生了 基因的丢失。在辐鳍鱼类和基底肉鳍鱼类中，由 基因在NKB旁边编码的NKB-RP肽在祖先羊膜动物中可能已经丢失。通过特异性定量PCR分析，鳗鲡 和 基因的mRNA组织分布显示这两种转录本在大脑中主要表达，尤其是在间脑中。已经在鳗鲡垂体细胞的原代培养物上测试了人类NKB。人类NKB剂量依赖性地抑制 的表达，而对其他糖蛋白激素亚基（ 、 和 ）以及 没有影响。人类NKB还剂量依赖性地抑制GnRH受体（r2）的表达。已经合成并测试了这四种鳗鲡肽。它们都抑制了 和 的表达。这揭示了由两个 基因编码的四种肽在鳗鲡生殖中潜在的双重抑制作用，在垂体水平对促黄体生成素和GnRH受体都有作用。
