The state of art on the immune and neuroendocrine functions of corticotrophin-releasing hormone and urocortin in invertebrates

Corticotrophin-releasing hormone (CRH) and urocortin (UCN) are well-known peptides whose functions, in mammals, include different aspects of stress-response, such as the activation of the hypothalamus-hypophysis-adrenal gland axis and the reduction of the appetite, respectively. Expecially in vertebrates, numerous sequences are now available for CRH, UCN and their paralogs that are collectively dubbed as CRH-family members.Together with a better understanding of their functions, the increased availability of CRHfamily member sequences allowed sequence comparison and the consequent flourishing of evolutive hypotheses. Even if problems and conundrums still persist about the origin and the diversification of the CRH-family components, there is growing evidence that this family of peptides, the related receptors and their binding proteins evolved before the split of deuterostomian and protostomian lineages. In invertebrates, CRH-like molecules have been isolated and described mainly in insects whereas no sequence information have so far been derived from other models, such as molluscs or annelids. In insects, the molecules considered as the most probable paralogs of vertebrate CRH-family members are usually ascribed to the group of diuretic hormones. However, in numerous invertebrate taxa, morphological, functional and molecular data indicate the presence of CRH and/or UCN orthologs in circulating and immune-related cell types, that we refer to as immunocytes. Here we review the evidence connecting the presence of invertebrate CRH- and UCN-like peptides to the immune and neuroendocrine system, suggesting that their involvement with the stress response is probably one of their most primitive characteristic, despite the different anatomical scenario within which the stress response occurs in divergent metazoan taxa.