Department of Cell and Systems BiologyUniversity of Toronto, 25 Harbord Street, Toronto, Ontario, Canada L4A IK6Department of Ecology and EvolutionUniversity of Toronto, Toronto, Ontario, CanadaDepartment of Life SciencesUniversity of Toronto Scarborough, Toronto, Ontario, Canada
Department of Cell and Systems BiologyUniversity of Toronto, 25 Harbord Street, Toronto, Ontario, Canada L4A IK6Department of Ecology and EvolutionUniversity of Toronto, Toronto, Ontario, CanadaDepartment of Life SciencesUniversity of Toronto Scarborough, Toronto, Ontario, CanadaDepartment of Cell and Systems BiologyUniversity of Toronto, 25 Harbord Street, Toronto, Ontario, Canada L4A IK6Department of Ecology and EvolutionUniversity of Toronto, Toronto, Ontario, CanadaDepartment of Life SciencesUniversity of Toronto Scarborough, Toronto, Ontario, Canada.
J Mol Endocrinol. 2014 Jun;52(3):T43-60. doi: 10.1530/JME-13-0238. Epub 2014 Apr 7.
Corticotrophin-releasing hormone (CRH) is the pivotal neuroendocrine peptide hormone associated with the regulation of the stress response in vertebrates. However, CRH-like peptides are also found in a number of invertebrate species. The origin of this peptide can be traced to a common ancestor of lineages leading to chordates and to arthropods, postulated to occur some 500 million years ago. Evidence indicates the presence of a single CRH-like receptor and a soluble binding protein system that acted to transduce and regulate the actions of the early CRH peptide. In vertebrates, genome duplications led to the divergence of CRH receptors into CRH1 and CRH2 forms in tandem with the development of four paralogous ligand lineages that included CRH; urotensin I/urocortin (Ucn), Ucn2 and Ucn3. In addition, taxon-specific genome duplications led to further local divergences in CRH ligands and receptors. Functionally, the CRH ligand-receptor system evolved initially as a molecular system to integrate early diuresis and nutrient acquisition. As multicellular organisms evolved into more complex forms, this ligand-receptor system became integrated with the organismal stress response to coordinate homoeostatic challenges with internal energy usage. In vertebrates, CRH and the CRH1 receptor became associated with the hypothalamo-pituitary-adrenal/interrenal axis and the initial stress response, whereas the CRH2 receptor was selected to play a greater role in diuresis, nutrient acquisition and the latter aspects of the stress response.
促肾上腺皮质激素释放激素（CRH）是与脊椎动物应激反应调节相关的关键神经内分泌肽激素。然而，许多无脊椎动物物种中也发现了类似 CRH 的肽。这种肽的起源可以追溯到导致脊索动物和节肢动物的谱系的共同祖先，据推测发生在大约 5 亿年前。有证据表明存在单一的 CRH 样受体和可溶性结合蛋白系统，该系统作用于转导和调节早期 CRH 肽的作用。在脊椎动物中，基因组加倍导致 CRH 受体与 CRH1 和 CRH2 形式的分化，同时还出现了包括 CRH 在内的四个同源配体谱系的平行分化。此外，分类特异性基因组加倍导致 CRH 配体和受体的进一步局部分化。从功能上讲，CRH 配体-受体系统最初作为一个分子系统进化，用于整合早期利尿和营养获取。随着多细胞生物进化成更复杂的形式，这种配体-受体系统与生物体的应激反应相结合，以协调与内部能量使用相关的同态挑战。在脊椎动物中，CRH 和 CRH1 受体与下丘脑-垂体-肾上腺/间肾轴和初始应激反应相关，而 CRH2 受体被选择在利尿、营养获取和应激反应的后期方面发挥更大的作用。
