Cerdá-Reverter, J.M., Agulleiro, M.J., R, R.G., Sánchez, E., Ceinos, R., and Rotllant, J. (2011) Fish melanocortin system. European Journal of Pharmacology. 660(1):53-60.
Melanocortin signalling is mediated by binding to a family of G protein-coupled receptors that positively couple to adenylyl cyclase. Tetrapod species have five melanocortin (MC(1)-MC(5)) receptors. The number of receptors varies in fish, zebrafish, for example, having six melanocortin receptors, with two copies of the melanocortin MC(5) receptor, while pufferfish have 4 receptors with no melanocortin MC(3) receptor and one copy of melanocortin MC(5) receptor. Fish genomes also exhibit orthologue genes for agouti-signalling protein (ASP) and -related protein (AGRP). AGRP expression is confined to a small area in the hypothalamus but ASP is expressed in the skin. Fish melanocortin MC(2) receptor is specific for ACTH and requires the cooperation of accessory proteins (MRAP) to reach functional expression. The four other melanocortin MC receptors distinctively bind MSHs. The interaction of α-MSH and melanocortin MC(1) receptor plays a key point in the control of the pigmentation and mutations of melanocortin MC(1) receptor are responsible for reduced melanization. Both melanocortin MC(4) and MC(5) receptor are expressed in the hypothalamus, and central melanocortin MC(4) receptor expression is thought to regulate the energy balance through the modulation of feeding behaviour. In addition, the peripheral melanocortin system also regulates lipid metabolism by acting at hepatic melanocortin MC(2) and MC(5) receptors. Both sea bass melanocortin MC(1) and MC(4) receptors are constitutively expressed in vitro and both ASP and AGRP work as inverse agonists but only after inhibition of the phosphodiesterase system. Accordingly, the overexpression of AGRP and ASP transgenes promotes obesity and reduces melanization in zebrafish, respectively.