Phylogeny of the corticotropin-releasing factor family of peptides in the metazoa

The corticotropin-releasing factor (CRF) family of peptides consists of four distinct paralogs found on separate chromosomes in vertebrates. Among invertebrates, the family has been relatively well characterized in the insects where at least 2 or 3 paralogs, a CRF-binding protein ortholog and a CRF receptor variant have been found. The conservation of structure and function of this system in insects imply that the CRF system evolved in ancestral species well before the Precambrian explosion. The CRF family peptides association with diuresis and feeding may have developed early in its evolution. However, CRF’s role in the hypothalamo–pituitary–adrenal axis and regulation of the glucocorticoids in association with energy metabolism appears to have developed in the chordate lineage.