Melanocortin 4 receptor distribution in the human hypothalamus

Abstract

ObjectiveThe melanocortin 4 receptor (MC4R) is an essential regulator of energy homeostasis and metabolism, andMC4Rmutations represent the most prevalent monogenetic cause of obesity in humans known to date. Hypothalamic MC4Rs in rodents are well characterized in neuroanatomical and functional terms, but their expression pattern in the human hypothalamus is unknown.Design and methodsTo determine the topographic distribution and identity of cells expressingMC4RmRNA in the human hypothalamus, locked nucleic acidin situhybridization was performed on nine human postmortem hypothalami. In addition, co-expression ofMC4Rwith glial fibrillary acidic protein (GFAP), vasopressin/oxytocin (AVP/OXT), corticotropin-releasing hormone (CRH), neuropeptide Y (NPY), agouti-related protein (AgRP), and α-melanocyte stimulating hormone (α-MSH) was examined.ResultsMost intenseMC4RmRNA expression was present in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and the nucleus basalis of Meynert. MostMC4R-positive cells in the SON also expressed AVP/OXT. Co-expression with AVP/OXT in the PVN was less abundant. We did not observe co-expression ofMC4RmRNA and GFAP, CRH, NPY, AgRP, or α-MSH. However, fiber-like staining of NPY, AgRP, and α-MSH was found adjacent toMC4R-positive cells in the PVN.ConclusionExpression ofMC4RmRNA in the human hypothalamus is widespread and in close approximation to endogenous MC4R binding partners AgRP and α-MSH.