Melanocyte-stimulating hormone


The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone, β-melanocyte-stimulating hormone, and γ-melanocyte-stimulating hormone that are produced by cells in the pars intermedia of the anterior lobe of the pituitary gland.
Synthetic analogues of α-MSH, such as afamelanotide, melanotan II, and bremelanotide, have been developed and researched.

Biosynthesis

The various forms of MSH are generated from different cleavages of the proopiomelanocortin protein, which also yields other important neuropeptides like adrenocorticotropic hormone.
Melanocytes in skin make and secrete MSH in response to ultraviolet light, where it increases synthesis of melanin. Some neurons in arcuate nucleus of the hypothalamus make and secrete α-MSH in response to leptin; α-MSH is also made and secreted in the anterior lobe of the pituitary gland.

Function

Acting through melanocortin 1 receptor, α-MSH stimulates the production and release of melanin by melanocytes in skin and hair.
Acting in the hypothalamus, α-MSH suppresses appetite. α-MSH secreted in the hypothalamus also contributes to sexual arousal.

In amphibians

In some animals production of MSH is increased when the animal is in a dark location. This causes pigment to be dispersed in pigment cells in the toad's skin, making it become darker, and harder for predators to spot. The pigment cells are called melanophores and therefore, in amphibians, the hormone is often called melanophore-stimulating hormone.

In humans

An increase in MSH will cause darker skin in humans too. MSH increases in humans during pregnancy. This, along with increased estrogens, causes increased pigmentation in pregnant women. Cushing's disease due to excess adrenocorticotropic hormone may also result in hyperpigmentation, such as acanthosis nigricans in the axilla. Most people with primary Addison's disease have darkening of the skin, including areas not exposed to the sun; characteristic sites are skin creases, nipple, and the inside of the cheek, new scars become hyperpigmented, whereas older ones do not darken. This occurs because MSH and ACTH share the same precursor molecule, proopiomelanocortin.
Different levels of MSH are not the major cause of variation in skin colour. However, in many red-headed people, and other people who do not tan well, there are variations in their hormone receptors, causing them to not respond to MSH in the blood.

Structure of MSH

The different forms of MSH belong to a group called the melanocortins. This group includes ACTH, α-MSH, β-MSH, and γ-MSH; these peptides are all cleavage products of a large precursor peptide called proopiomelanocortin. α-MSH is the most important melanocortin for pigmentation.
The different forms of MSH have the following amino acid sequences:
α-MSH:Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val
β-MSH :Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
β-MSH :Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
γ-MSH:Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly

Synthetic MSH

Synthetic analogues of α-MSH have been developed for human use. Two of the better known are afamelanotide in testing by Clinuvel Pharmaceuticals and bremelanotide by Palatin Technologies. Others include modimelanotide and setmelanotide.