Melanin-concentrating hormone (MCH) is a 19 amino acid peptide originally isolated from the salmon pituitary gland (in fish the length of the peptide is 17 amino acids)¹. In rodents and humans the peptide is synthesized in the brain and is involved in a number of physiological effects, although it is best known for its central role in the control of appetite control. For example, central administration of MCH in mice leads to obesity and conversely, knockout of the MCH gene in mice yields lean animals with an increased metabolic rate and reduced body fat^2,3.

MCH exerts its effects by binding MCHR1 and MCHR2, two receptors belonging to the superfamily of G-protein coupled receptors (GPCRs). Like all members of the family, MCHR1 and MCHR2 have seven transmembrane domains, an extracellular N-terminal and intracellular C-terminal tails. MCHR1 and MCHR2 activation both lead to an increase in intracellular Ca²⁺ concentration³.

In rat, MCHR1 expression is quite broad, and is strongly detected in the brain. Expression of the receptor is also seen in the eye, skeletal muscle, tongue, pituitary, intestine and lymphocytes^4,5. MCHR1 is also expressed in adipose tissue where it regulates leptin secretion³. In human, MCHR1 is mostly localized to the brain and pituitary. MCHR2 displays similar localization to that of MCHR1 in the brain^5,6. As MCHR2 is a pseudogene in rodents, studying its function is quite challenging. 

In the brain, MCHR1 is localized in many areas that are known to be involved in various psychological disorders. Indeed, MCHR1^-/- animals display antianxiety- and antidepressant-like behavior^7,8. Therefore, antagonizing the activity of MCHR1 could indeed serve as a means to treat depression and obesity⁹.