Abstract
Prolactin-releasing peptide (PrRP) is one of the RF-amide peptides and was originally identified in the bovine hypothalamus as a stimulator of prolactin (PRL) release. Independently, another RF-amide peptide was found in Japanese crucian carp and named Carassius-RFa (C-RFa), which shows high homology to PrRP and stimulates PRL secretion in teleost fish. Therefore, C-RFa has been recognized as fish PrRP. However, recent work has revealed that PrRP and C-RFa in non-mammalian vertebrates are encoded by separate genes originated through duplication of an ancestral gene. Indeed, both PrRP and C-RFa are suggested to exist in teleost, amphibian, reptile, and avian species. Therefore, we propose that non-mammalian PrRP (C-RFa) be renamed PrRP2. Despite a common evolutionary origin, PrRP2 appears to be a physiological regulator of PRL, whereas this is not a consistent role for PrRP itself. Further work revealed that the biological functions of PrRP and PrRP2 are not limited solely to PRL release, because they are also neuromodulators of several hypothalamus–pituitary axes and are involved in some brain circuits related to the regulation of food intake, stress, and cardiovascular functions. However, these actions appear to be different among vertebrates. For example, central injection of PrRP inhibits feeding behavior in rodents and teleosts, while it stimulates it in chicks. Therefore, both PrRP and PrRP2 have acquired diverse actions through evolution. In this review, we integrate the burgeoning information of structures, expression profiles, and multiple biological actions of PrRP in higher vertebrates, as well as those of PrRP2 in non-mammals.
Highlights
DISCOVERY OF PROLACTIN-RELEASING PEPTIDES Hinuma et al [1] first identified a peptide, which is a ligand of the orphan 7-transmembrane receptor hGR3, by using a reversepharmacological technique
CONCLUDING REMARKS Prolactin-releasing peptide was originally identified as a stimulator of PRL release in mammals
Further work revealed that prolactinreleasing peptide (PrRP) had less effect on PRL release, PrRP has been shown to be involved in many physiological actions, such as reproduction, endocrine functions, feeding behavior and metabolism, and stress response in mammals, and possibly in other vertebrates (Table 2)
Summary
Human PrRP genes are located on chromosomes 9q36 and 2q37.3, respectively. The genomic organization and promoter function of the rat PrRP gene have been examined by Yamada et al [6]. Based on PrRP genes in non-mammalian vertebrates, the amino acid sequence of their preproPrRPs was predicted and its sequence showed low-to-moderate homology to mammalian PrRP. C-RFa homologs were isolated from several teleosts, such as chum salmon and tilapia, and their amino acid sequences are identical to the crucian carp [7,8,9] This amino acid sequence shows similarity to those of mammalian PrRP-20 (Figure 1). Chicken and X. tropicalis preproPrRP2, respectively, have low homology with their preproPrRP [5, 15] Their amino acid sequences suggest the occurrence of a longer form of PrRP2 such as PrRP2-31 in X. laevis [16] as shown in chickens. These PrRP-Rs share a slight homology with the neuropeptide Y (NPY) receptor in amino acid sequences, and a micromolar level
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