Melanocyte-stimulating hormone

The melanocyte-stimulating hormones (collectively referred to as MSH or intermedins) are a class of peptide hormones that in nature are produced by cells in the intermediate lobe of the pituitary gland. Synthetic analogs of these naturally occurring hormones have also been developed and researched.

Function
They stimulate the production and release of melanin (melanogenesis) by melanocytes in skin and hair. MSH signals to 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
An increase in MSH will cause a darkening in humans too. Melanocyte-stimulating hormone 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 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), also old scars may darken. This occurs because melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) share the same precursor molecule, Pro-opiomelanocortin (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.

See melanocortin receptor for more information.

Structure of MSH
Melanocyte-stimulating hormone belongs to a group called the melanocortins. This group includes ACTH, alpha-MSH, beta-MSH and gamma-MSH; these peptides are all cleavage products of a large precursor peptide called pro-opiomelanocortin (POMC). Alpha-MSH is the most important melanocortin for pigmentation.

The different melanocyte-stimulating hormones have the following amino acid sequences:

Synthetic MSH
Synthetic analogs of alpha-MSH have been developed for human use. Two of the better known are afamelanotide (melanotan-1) in testing by Clinuvel Pharmaceuticals in Australia and bremelanotide by Palatin Technologies, a New Jersey company.


 * Afamelanotide (formerly CUV1647) is being investigated as a method of photoprotection in patients with erythropoietic protoporphyria, polymorphous light eruption, actinic keratosis and squamous cell carcinoma (a form of skin cancer).


 * An additional analog called Melanotan II causes enhanced libido and erections in most male test subject and arousal with corresponding genital involvement in most female test subjects. Bremelanotide (formerly PT-141) which stemmed from Melanotan II research was previously under development by the New Jersey company for its aphrodisiac effects. These effects are mediated by actions in the hypothalamus on neurons that express MC3 and MC4  receptors.