Melanocortin 3 receptor (MC3R) (MC3R)

The Melanocortin 3 receptor (MC3R) is a G protein-coupled receptor (GPCR) primarily expressed in the central nervous system, particularly within the hypothalamic arcuate nucleus, as well as in peripheral tissues like the heart, kidney, and immune cells [3, 5, 7]. It is uniquely characterized by its high affinity for gamma-melanocyte-stimulating hormone (gamma-MSH) peptides, such as gamma3-MSH, which are its most selective endogenous agonists [1, 5, 8]. MC3R plays a pivotal role in energy homeostasis by acting as a metabolic rheostat that regulates nutrient partitioning, favoring the accumulation of lean mass over fat mass [4, 5, 19]. In the brain, it functions as an inhibitory autoreceptor on pro-opiomelanocortin (POMC) neurons, providing a feedback mechanism to modulate the activity of the melanocortin system [3, 6, 10]. Beyond metabolism, MC3R is involved in regulating the timing of puberty, linear growth, circadian rhythms, and cardiovascular functions such as blood pressure and natriuresis [5, 9, 15]. It also exhibits significant anti-inflammatory properties, making it a target for treating conditions like gout and rheumatoid arthritis [13, 18]. Genetic variants and loss-of-function mutations in MC3R are linked to obesity, delayed puberty, and metabolic syndrome [19, 20].

Other names

MC3-RMelanocortin receptor 3BMIQ9OB20OQTL

Activation of the MC3R by agonists like gamma3-MSH stimulates the Gs-protein/adenylyl cyclase pathway, increasing intracellular cAMP levels. It also acts as an inhibitory autoreceptor on POMC neurons in the hypothalamus to regulate the central melanocortin system.