Melanocortin System
Definition
The melanocortin system is a neuroendocrine signalling network centred on five melanocortin receptors (MC1R–MC5R) and their peptide ligands derived from proopiomelanocortin (POMC). It regulates diverse physiological functions including pigmentation, energy homeostasis, inflammation, sexual function, and adrenal steroidogenesis.
Components and Receptors
The system comprises:
- MC1R — Expressed in melanocytes; regulates skin and hair pigmentation. Target of α-MSH and afamelanotide
- MC2R — The ACTH receptor on adrenal cortex; regulates cortisol production
- MC3R — Expressed in the hypothalamus and gut; involved in energy homeostasis and nutrient partitioning
- MC4R — Key hypothalamic receptor for appetite regulation and energy expenditure. Mutations cause monogenic obesity
- MC5R — Found in exocrine glands; role in sebaceous gland function
Endogenous ligands include α-MSH, β-MSH, γ-MSH, and ACTH (agonists) and agouti-related peptide (AgRP, an inverse agonist at MC3R/MC4R).
Relevance to Peptide Research
Multiple research peptides target melanocortin receptors. Melanotan II and PT-141 (bremelanotide) are non-selective melanocortin agonists studied for tanning and sexual function. Setmelanotide is a selective MC4R agonist approved for rare genetic obesity. The melanocortin system’s breadth — spanning pigmentation, appetite, inflammation, and sexual function — makes it one of the most pharmacologically targeted peptide receptor families.
Related Peptides
Peptide profiles that reference “Melanocortin System” in their research content.