Regulation of melanocortin 1 receptor expression at the mRNA and protein levels by its natural agonist and antagonist

Five melanocortin receptors, which form a subfamily of G protein-coupled receptors, are expressed in mammalian tissues and regulate such diverse physiological processes as pigmentation, adrenal function, energy homeostasis, feeding efficiency, and sebaceous gland lipid production, as well as immune and sexual function. Pigmentation in mammals is stimulated by alpha-melanocyte stimulating hormone (MSH), which binds to the melanocortin 1 receptor (Mclr) and induces an activation of melanogenic enzymes through stimulation of adenylate cyclase and protein kinase A. The antagonist agouti signal protein (ASP) interacts with the Mclr and blocks its stimulation by MSH. We examined the influence of ASP or MSH on Mclr gene expression, and we report that both ligands influence the Mclr 5' promoter structure in distinct manners. Our study further shows that MSH regulates Mclr function at both the mRNA and protein levels, whereas ASP acts only on its translation.