Lysipressin

Neurohypophyseal hormones of two species belonging to the family Dasyuridae, namely Dasyurus viverrinus (Eastern native cat) and Dasyuroides byrnei (Kowari), and of the single living member of the family Phascolarctidae, Phascolarctos cinereus (Koala) have been isolated and characterized by their retention times in high-pressure reverse-phase partition chromatography and either amino acid composition or amino acid sequence through a gas-phase microsequencer. Mesotocin and arginine vasopressin have been identified in the three species. The same hormones have previously been found in a species belonging to the family Phalangeridae, Trichosurus vulpecula (brush-tailed possum), whereas in five species of Macropodidae, mesotocin, lysipressin, and phenypressin have been characterized. Because the four Australian marsupial families examined up to now possess mesotocin and at least a vasopressin-like peptide, it is assumed that the primitive marsupial settler in Australia was endowed with mesotocin and arginine vasopressin.

Neurohypophysial hormones of an Australian marsupial, the Northern bandicoot (Isoodon macrourus), have been identified by their retention times in high-pressure reverse-phase liquid chromatography using two solvent systems and by their molar pressor or uterotonic activities. Two pressor peptides, arginine vasopressin and lysipressin, and two uterotonic peptides, mesotocin and oxytocin, have been characterized. Because mesotocin and arginine vasopressin have been identified in three other Australian marsupial families, it is assumed that a duplication of each ancestral gene occurred in Peramelidae and subsequent mutations in one copy led to the additional oxytocin and lysipressin. A similar dual duplication of neurohypophysial hormones has previously been discovered in the North-American opossum (Didelphis virginiana) so that the duplication propensity seems peculiar to marsupials in contrast to placental mammals.

Mesotocin ([Ile8]-oxytocin), lysipressin ([ Lys8]-vasopressin) and phenypressin ([Phe8]-vasopressin) have been identified in the western gray kangaroo (Macropus fuliginosus) as well as four other macropodids. Lysipressin and phenypressin, which differ by the amino acids in positions 2 (Tyr/Phe) and 8 (Lys/Arg) are likely products of two separate vasopressin-like genes. It is assumed that arginine vasopressin found in most mammals is the product of two identical genes which can be revealed in some species by differential mutations as seen usually in marsupials. The duality can also be revealed by differential mutations in another domain of the precursors, such as the neurophysin (MSEL-neurophysin), as observed in the ox.

Oxytocin, mesotocin ([Ile8]-oxytocin), lysipressin ([Lys8]-vasopressin) and arginine vasopressin have been identified in the North American opossum (Didelphis virginiana) by amino acid composition and high pressure liquid chromatography. The same peptides with the exception of mesotocin have previously been found in two South American opossums (Didelphis marsupialis and Philander opossum). Although a dual heterozygocity could also explain the simultaneous presence of oxytocin/mesotocin on one hand, lysipressin/arginine vasopressin on the other, it is assumed, from the results obtained with individual glands of Australian and South American marsupials, that distinct genes encode for the four peptides.

The neurohypophyseal hormones of the hippopotamus (Hippopotamus amphibius) and collared peccary (Tayassu angulatus) were isolated by molecular sieving and preparative high-pressure liquid chromatography (HPLC). Oxytocin and arginine vasopressin have been identified by their amino acid compositions and their retention times in HPLC. Lysipressin (lysine vasopressin) was not detected in posterior pituitaries of two hippopotami and nine peccaries (less than 2% of arginine vasopressin in molar ratios). Among the suborder Suiformes of Artiodactyla, the families Hippopotamidae and Tayassuidae do not seem to possess lysipressin, in contrast to the family Suidae in which the pig has lysipressin in place of arginine vasopressin.

Neurohypophysial hormones are particularly proper evolutionary tracers. Whereas Eutherian mammals have oxytocin and virtually always arginine vasopressin, nonmammalian tetrapods possess instead mesotocin and vasotocin. The transitions of mesotocin-oxytocin and vasotocin-vasopressin involved in the passage of reptiles-mammals seem to have occurred independently. Australian marsupials are endowed with mesotocin but American marsupials have either oxytocin (South-American opossums) or both oxytocin and mesotocin (North-American opossum). These results suggest that Australian Metatherians have preserved reptilian mesotocin and used it for milk-ejecting function whereas the change mesotocin-oxytocin appeared only in the American line. All marsupials have either arginine vasopressin or lysipressin and phenypressin (Australians) or lysipressin and arginine vasopressin (Americans). It is assumed that the change of vasotocin into arginine vasopressin occurred very early, perhaps in mammal-like reptiles, and duplication of the gene with subsequent mutations has led to the presence of two vasopressin-like peptides in most Metatherians.

Neurohypophysial hormones and neurophysins are derived from common precursors processed during the axonal transport from the hypothalamus to the neurohypophysis. Two neurohormones, an oxytocin-like and a vasopressin-like, on one hand, two neurophysins, termed VLDV-and MSEL-neurophysins according to residues in positions 2, 3, 6 and 7, on the other, are usually found in vertebrate species. In contrast to placental mammals that have oxytocin and arginine vasopressin, marsupials have undergone a peculiar evolution. Two pressor peptides, lysipressin and vasopressin for American species, lysipressin and phenylpressin for Australian macropods, have been identified in individual glands and it is assumed that the primordial vasopressin gene has been duplicated in these lineages. On the other hand, the reptilian mesotocin is still present in Australian species instead of the mammalian oxytocin, while the North American opossum has both hormones and South American opossums have only oxytocin. The neurophysin domain of each precursor is encoded by 3 exons and different evolutionary rates have been found for the 3 corresponding parts of the protein. The central parts, encoded by the central exons, are evolutionarily very stable and nearly identical in the 2 neurophysins of a given species. Recurrent gene conversions have apparently linked the evolutions of the 2 precursor lineages. In mammals, the 3-domain precursor of vasopressin is processed in 2 stages: a first cleavage splitting off vasopressin and a second cleavage separating MSEL-neurophysin from copeptin. Two distinct enzymatic systems seem to be involved in these cleavages. Processing is usually complete at the level of the neurohypophysis, but an intermediate precursor encompassing MSEL -neurophysin and copeptin linked by an arginine residue has been characterized in guinea pig. In vitro processing of this intermediate through trypsin--Sepharose reveals cleavages only in the interdomain region. In non-mammalian tetrapods, such as birds and amphibians, mesotocin and vasotocin are associated with neurophysins in precursors similar to those found in mammals. However, processing of the vasotocin precursor seems to be different from the processing of the vasopressin precursor, with a single cleavage leading to the hormone release.