Elucidation of reproductive endocrine system in hagfish

鳗鱼既没有颌骨也没有脊椎骨，被认为是已知的最原始的脊椎动物，要么存活，要么灭绝。鳗鱼长期以来一直是脊椎动物进化的谜团，这不仅是因为它们的进化地位，也是因为我们对基本过程缺乏了解。鳗鱼生殖内分泌系统的关键因素尚未阐明。在此，我们首次从八目鳗的脑垂体中鉴定出一种促性腺激素(GTH)。鳗鱼GTH由α和β两个亚基组成，这两个亚基是在腺垂体的同一细胞中合成和共存的。鳗鱼Gth、α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体外诱导性类固醇释放。根据我们的系统发育分析，我们认为脊椎动物糖蛋白激素家族的Gthα和Gthβ分别是由祖先的甲状腺刺激素α亚基和β亚基引起的。我们假设，鳗鱼的单一功能GTH的同一性为最早的分叉脊椎动物中存在脑垂体-性腺系统提供了关键证据，该系统可能是从祖先、前脊椎动物特有的神经内分泌机制进化而来的，其进化过程是通过逐渐出现一个新的控制水平，即在原脊椎动物中没有的脑下垂体。

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.