Melanocortin receptor

Group of G-protein coupled receptors that mediate the effects of melanocortins - melanotropins (MSH) and adrenocorticotropin (ACTH). 5 melanocortin receptors have been described so far. They are abbreviated as MC1R - MC5R. 2 endogenous antagonists of the melanocortin system are known. Agouti and AGRP.

Melanocortin-1-receptor (MC1R): is expressed on melanocytes and controls skin tanning. This receptor is encoded by the extension locus. After stimulation by alpha-MSH, the MC1 receptor activates a complex signalling cascade leading to melanin (eumelanin) production. This activation can be antagonized by the agouti-signal protein (ASIP).

Melanocortin 2 receptor (MC2R): Also known as ACTH receptor. MC2R is found in the adrenal cortex where it mediates the effects of ACTH (release of glucocorticoids).

Melanocortin 3 receptor (MC3R): Expressed in the brain (particularly in the hypothalamus near the organum vasculosum laminae terminalis), the placenta, intestinal tissue, but not in the adrenal cortex or in melanocytes. MC3R is activated by alpha- beta-gamma melanocyte stimulating hormones and by ACTH.

Melanocortin-4-receptor (MC4R): This receptor is expressed (like MC3R) in the brain (there especially in regions of the hypothalamus near the organum vasculosum laminae terminalis) and in the intestine. MC4R is activated by alpha-MSH, beta-MSH and ACTH. MC4R is involved in the regulation of vegetative reactions and in the regulation of energy homeostasis (e.g. regulation of body temperature). Its activation leads to the suppression of the feeling of hunger and to an increase in libido. Mutations in the MC4R gene can be associated with obesity.

Melanocortin 5 receptor (MC5R): MC5R is expressed in numerous peripheral tissues, such as adrenal glands, adipocytes and leukocytes. Little is known about its effect. It is involved in the exocrine function, especially of the sebaceous glands.

In addition to its effect on MC2R, ACTH is a potent agonist for all melanocortin receptors. Alpha-MSH is an agonist for MC1R, MC3R and MC4R, gamma-MSH is only the agonist for MC3R.

• Melanocortin-1 receptor (MC1R): is expressed on melanocytes and controls skin tanning. This receptor is encoded by the extension locus. After stimulation by alpha-MSH, the MC1 receptor activates a complex signalling cascade leading to melanin (eumelanin) production. This activation can be antagonized by the agouti-signal protein (ASIP).
• Melanocortin 2 receptor (MC2R): Also known as ACTH receptor. MC2R is found in the adrenal cortex where it mediates the effects of ACTH (release of glucocorticoids).
• Melanocortin 3 receptor (MC3R): Expressed in the brain (particularly in the hypothalamus near the organum vasculosum laminae terminalis), the placenta, intestinal tissue, but not in the adrenal cortex or in melanocytes. MC3R is activated by alpha- beta-gamma melanocyte stimulating hormones and by ACTH.
• Melanocortin-4-receptor (MC4R): This receptor is expressed (like MC3R) in the brain (there especially in regions of the hypothalamus near the organum vasculosum laminae terminalis) and in the intestine. MC4R is activated by alpha-MSH, beta-MSH and ACTH. MC4R is involved in the regulation of vegetative reactions and in the regulation of energy homeostasis (e.g. regulation of body temperature). Its activation leads to the suppression of the feeling of hunger and to an increase in libido. Mutations in the MC4R gene can be associated with obesity.
• Melanocortin 5 receptor (MC5R): MC5R is expressed in numerous peripheral tissues, such as adrenal glands, adipocytes and leukocytes. Little is known about its effect. This receptor is involved in the exocrine function of the sebaceous glands in particular.

1. Elincx-Benizri S et al (2014) The Melanocortin 1 Receptor (Mc1r) Variants Do Not Account for the Co-occurrence of Parkinson's Disease and Malignant Melanoma. J Mol Neurosci 54:820-825
2. Taylor NJ et al (2014) Inherited variation at MC1R and ASIP and association with melanoma-specific survival. Int J Cancer doi: 10.1002/ijc.29317