Elucidation of reproductive endocrine system in hagfish

盲鳗既没有颌也没有椎骨，被认为是已知的最原始的脊椎动物，无论是现存的还是灭绝的。盲鳗长期以来一直是脊椎动物进化的谜，这不仅是因为它们的进化位置，还因为我们对其基本过程缺乏了解。盲鳗生殖内分泌系统的关键因素尚未阐明。在这里，我们报告了首次从盲鳗的垂体中鉴定出促性腺激素（GTH）。盲鳗GTH由α和β两个亚基组成，它们合成并共定位于腺垂体的同一细胞中。盲鳗GTHα和β的细胞活性和转录活性与性腺发育阶段显著相关。纯化的天然GTH在体外诱导性腺激素的释放。从我们的系统发育分析中，我们提出祖先的甲状腺激素α亚基和β亚基分别产生脊椎动物糖蛋白激素家族的GTHα和GTHβ。我们假设盲鳗的单一功能GTH的识别为最早的脊椎动物中存在垂体-性腺系统提供了关键证据，该系统可能是从祖先的，前脊椎动物的神经内分泌机制进化而来的，通过逐渐出现新的控制水平，垂体，这在原脊索动物中没有发现。

Hagfishes, which lack both jaws and vertebrae, are considered the most primitive vertebrate known, living or extinct. Hagfishes have long been the enigma of vertebrate evolution not only due to their evolutionary position but also due to our lack of knowledge on fundamental processes. Key elements of the reproductive endocrine system in hagfish have yet to be elucidated. Here we report the first identification of a gonadotropic hormone (GTH) from the pituitary of the hagfish Paramyxine atami. The hagfish GTH consists of two subunits, α and β, which are synthesized and colocalized in the same cells of the adenohypophysis. The cellular and transcriptional activities of hagfish GTHα and β were significantly correlated with the developmental stages of the gonad. The purified native GTH induced the release of gonadal sex steroids in vitro. From our phylogenetic analysis, we propose that ancestral thyrostimulin alpha subunit and beta subunit gave rise to GTHα and GTHβ of the vertebrate glycoprotein hormone family, respectively. We hypothesize that the identity of a single functional GTH of the hagfish provides critical evidence for the existence of a pituitary-gonadal system in the earliest divergent vertebrate that likely evolved from an ancestral, pre-vertebrate exclusively neuroendocrine mechanism by gradual emergence of a new control level, the pituitary, that is not found in the Protochordates.