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The melanocyte-stimulating hormones (collectively referred to as MSH) are a class of peptide hormones produced by cells in the intermediate lobe of the pituitary gland.

They stimulate the production and release of melanin (melanogenesis) by melanocytes in skin and hair. MSH is also produced by a subpopulation of neurons in the arcuate nucleus of the hypothalamus. MSH released into the brain by these neurons has effects on appetite and sexual arousal.

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.

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. In Addison's disease high levels of adrenocorticotropic hormone (ACTH) production also leads to high MSH levels, which cause an abnormal darkening.

Different levels of MSH are not the major cause of racial variation in skin colour. 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.

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:

Two synthetic analogs of alpha-MSH, based upon a peptide called Melanotan are being developed for human use, one by an Australian company the other by a New Jersey company.

• Alpha-MSH topical cream is being investigated as a possible therapeutic aid in the treatment of melanoma.

• 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^{[citation needed]}. Bremelanotide (formerly PT-141) the peptide that is being developed by the New Jersey company is a close analog of melanotan II that shares its aphrodisiac effects and is currently in clinical trials to treat erectile dysfunction and sexual arousal disorder. These effects are mediated by actions in the hypothalamus on neurons that express MC3 MC3R and MC4 MC4R receptors.

• MeSH Melanocyte-Stimulating+Hormones