Distribution and function of melanocortin receptors within the brain

Abstract

Biological responses to pro-opiomelanocortin (POMC)-derived peptides administered in the brain were documented in the 1950s but their molecular mechanisms of action only began to be resolved with the mapping of melanocortin receptor subtypes to specific brain regions in the 1990s. Out of the five melanocortin receptor subtypes, MC3R and MC4R are widely recognised as 'neural' melanocortin receptors. In situ hybridization anatomical mapping of these receptor subtypes to distinct hypothalamic nuclei first indicated their roles in energy homeostasis, roles that were later confirmed with the obese phenotypes exhibited by Mc3R and Mc4R knockout mice. It is perhaps less well known however, that all five melanocortin receptor subtypes have been detected in developing and/or adult brains of various species. This chapter provides a comprehensive summary of the detection and mapping of each melanocortin receptor subtype in mammalian, chicken and fish brains and relates the sites of expression to functions that are either known or proposed for each receptor subtype.