Melanocyte-stimulating hormone

pro-opiomelanocortin
Identifiers
Symbol	POMC
Entrez	5443
HUGO	9201
OMIM	176830
RefSeq	NM_000939
UniProt	P01189
Other data
Locus	Chr. 2 p23

Melanocyte-stimulating hormone

Identifiers
ChEMBL	CHEMBL214332 N
NY (what is this?)  (verify)

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 (α-MSH), β-melanocyte-stimulating hormone (β-MSH), and γ-melanocyte-stimulating hormone (γ-MSH) that are produced by cells in the intermediate lobe of the pituitary gland.

Synthetic analogues of α-MSH, such as afamelanotide (melanotan I; Scenesse), melanotan II, and bremelanotide (PT-141), have been developed and researched.

Function

MSH stimulate the production and release of melanin (a process referred to as melanogenesis) by melanocytes in skin and hair. MSH actions in the brain have effects on appetite and sexual arousal.

In amphibians

In some animals (such as the claw-toed frog Xenopus laevis) 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

See also: Melanocortin receptor

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 syndrome due to excess adrenocorticotropic hormone (ACTH) may also result in hyperpigmentation, such as acanthosis nigricans in the axilla. Most people with primary Addison's disease have darkening (hyperpigmentation) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the hands), nipple, and the inside of the cheek (buccal mucosa), new scars become hyperpigmented, whereas older ones do not darken. This occurs because MSH and ACTH share the same precursor molecule, proopiomelanocortin (POMC).

Different levels of MSH are not the major cause of racial 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

proopiomelanocortin derivatives
POMC
γ-MSH	ACTH		β-lipotropin
	α-MSH	CLIP	γ-lipotropin		β-endorphin
				β-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 (POMC). 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 (human):	Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
β-MSH (porcine):	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 (melanotan I) in testing by Clinuvel Pharmaceuticals and bremelanotide by Palatin Technologies. Others include modimelanotide and setmelanotide.

• Afamelanotide (brand name Scenesse) has been approved for the treatment of erythropoietic protoporphyria in Europe and is also being investigated as a method of photoprotection in the treatment of polymorphous light eruption, actinic keratosis and squamous cell carcinoma (a form of skin cancer).

• An additional analogue called melanotan II causes enhanced libido and erections in most male test subjects and arousal with corresponding genital involvement in most female test subjects. Bremelanotide (formerly PT-141) which stemmed from melanotan II research is currently under development for its aphrodisiac effects. These effects are mediated by actions in the hypothalamus on neurons that express MC₃ and MC₄ receptors.

See also

• Melanocyte-inhibiting factor
• Agouti-related peptide
• Agouti signalling peptide
• Nelson's syndrome

External links

• Melanocyte-Stimulating Hormones at the US National Library of Medicine Medical Subject Headings (MeSH)
• Clinuvel Pharmaceuticals
• Palatin Technologies