The prolactin/vasoinhibin axis in humans features the generation, secretion, and actions of the pleiotropic pituitary hormones prolactin and vasoinhibins under control of the hypothalamus, the pituitary gland, and the target tissue microenvironment. Vasoinhibins are generated by proteolytic cleavage of full-length prolactin at various cleavage sites. The evolutionary history of vasoinhibins is largely unknown.
The prolactin protein sequences of the primate species Human, Chimpanzee, Gorilla, Orangutan, Gibbon, Vervet AGM, Olive baboon, Macaque, Marmoset, Tarsier, Bushbaby, and Mouse Lemur, and the prolactin gene tree were retrieved from the ENSEMBL data base. A multiple sequence alignment was performed, using Clustal Omega. Five known cleavage sites within the human prolactin protein sequence, defined by fully conserved sequence motifs required for the generation of vasoinhibins with molecular masses of 15, 16.8, 17.2, 17.7, and 18 kilodalton (kDa), were the focus of the comparison.
The prolactin protein sequence of all hominoidea (Human, Chimpanzee, Gorilla, Orangutan, and Gibbon) demonstrated the presence of all 5 cleavage sites present in the human sequence. Species from the taxon Old world monkeys (Vervet AGM, Olive baboon, Macaque) lack the cleavage site for the 17.2 kDa vasoinhibin. The marmoset (Simians) prolactin sequence does not feature the 16.8 kDa vasoinhibin cleavage site, the Tarsier (Dry nose primates) lacks the 16.8, and the 15 kDa cleavage sites, the Bushbaby the 15, 16.8, and the 17.7 kDa cleavage sites, and the Mouse Lemur (Wet nose lemurs) the 15 and 16.8 kDa cleavage sites.
The variation in the number of cleavage sites likely translates into a corresponding difference in the number of vasoinhibins present in the respective species. The ascending number of cleavage sites throughout primate evolution may represent prolactin gain-of-function events and constitutes an endocrinological distinctive feature between primates, which could affect the pleiotropic profile of biological effects of the prolactin/vasoinhibin axis.