Neuromedins U and S involvement in the regulation of the hypothalamo-pituitary-adrenal axis

Abstract

We reviewed neuromedin U (NMU) and neuromedin S (NMS) involvement in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis function. NMU and NMS are structurally related and highly conserved neuropeptides. They exert biological effects via two GPCR receptors designated as NMUR1 and NMUR2 which show differential expression. NMUR1 is expressed predominantly at the periphery, while NMUR2 in the central nervous system. Elements of the NMU/NMS and their receptors network are also expressed in the HPA axis and progress in molecular biology techniques provided new information on their actions within this system. Several lines of evidence suggest that within the HPA axis NMU and NMS act at both hypothalamic and adrenal levels. Moreover, new data suggest that NMU and NMS are involved in central and peripheral control of the stress response.

Keywords: adrenal; hypothalamus; neuromedin S; neuromedin U; pituitary.

Figure 1

Amino acid sequences of neuromedin U from some mammalian, avian, piscine, and amphibian species. The box, highlighting the C-terminal pentapeptide, shows conservation of this sequence in vertebrates, except of goldfish. From Mitchell et al. (2009a), modified. Amino acid sequences were acquired from NCBI. Numbers after NMU denote peptide length.

Figure 2

Amino acid sequences of neuromedin S from some mammalian and amphibian species. The box, highlighting the C-terminal decapeptide, shows conservation of this sequence in vertebrates. NMU and NMS share the same amidated C-terminal heptapeptide. Amino acid sequences were acquired from NCBI. Numbers after NMS denote peptide length.

Figure 3

Schematic structure of prepro-NMU and prepro-NMS in humans. Data from Protein Knowledgebase (UniProtKB) P48645 and Q5H8A3, respectively. Schematic structure of prepro-NMU is modified from Austin et al. (1995). Numbers refer to residues and cleavage sites are given in red. Asterisk marks amidated asparagine.

Figure 4

Schematic representation of human NMUR1 and NMUR2 receptors. NMUR1 receptor is composed of 426 amino acid residues while NMUR2 of 415. Amino acid sequences were acquired from NCBI, accession numbers AAG24793.1 and EAW61653.1, respectively.