Ontogeny and phylogeny of neuropeptides: Protein precursors and enzymic processing

Abstract

Neurohypophysial hormones are nonapeptides derived from precursors containing two or three domains, namely the hormonal moiety, a small protein, neurophysin (93/95 residues) and occasionally a glycopeptide, copeptin (39 residues). Enzymic processing of the precursors is very fast and separate domains are usually found in neurohypophysis. These fragments can be used on one hand to trace two phylogenetic lineages in vertebrates, on the other hand to follow expression of the precursor genes during the early stages of development. Regarding the hormonal domains, whereas mammalian species possess virtually always vasopressin and oxytocin, nonmammalian tetrapods have vasotocin ([Ile 3]-vasopressin) and mesotocin ([Ile 8]-oxytocin). Concerning the neurophysin domains, the two types MSEL-neurophysin (vasopressin-associated) and VLDV-neurophysin (oxytocin-associated) identified in mammals, have been also detected in nonmammalian tetrapods suggesting the association of MSEL-neurophysin with vasotocin and VLDV-neurophysin with mesotocin. About copeptin, recognition in lower vertebrates is difficult, likely because of a high number of substitutions. The three distinct domains correspond roughly to separate coding regions within the genes and could therefore have had autonomous evolutionary histories. Studies carried out with bovine fetus at the ages of 3 and 7 months reveal the same neuropeptides as those identified in the adult, but vasopressin gene is expressed 3 and 4 times more than oxytocin gene whereas in the adult both genes are roughly equally productive. This research fails, however, to identify vasotocin in fetus and to demonstrate a molecular recapitulation of neurohypophysial hormones, as previously suggested on the basis of pharmacological and immunological data.