Melanocyte-stimulating hormone (MSH) - Melanotropin hormone

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What is melanocyte-stimulating hormone?

The melanocyte-stimulating hormones (aka MSH, intermedin or melanotropin) are a group of naturally occurring peptide hormones.

Melanotropin peptides are primarily produced and secreted by the pituitary gland. The hypothalamus and skin cells (keratinocytes) also contribute to the production of the melanotropin hormone. Though the main function of melanotropin hormones is in stimulating the melanocytes to produce melanin, they have been found to be effective in reducing appetite and in increasing the libido.

Melanotropin peptides belong to the peptide group known as melanocortins. The precursor of melanotropin is a larger peptide known as pro-opiomelanocortin (POMC). POMC is cleaved to form three fragments, one of which is adrenocorticotropic hormone (ACTH or corticotropin). ACTH can be further fragmented to form alpha melanocyte stimulating hormone. The remaining two fragments of POMC cleave to form beta-M-S hormone and gamma-M-S hormone. The alpha type of hormone has 13 amino acids, whereas the beta and gamma types of melanotropin have 18 and 11 amino acids respectively.

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Research organizations have developed synthetic analogs of melanotropin and are experimenting on their utility in melanin production as well as many other fields of human pathophysiology. Afamelanotide (melanotan-1) is a synthetic melanotropin being researched for photoprotection of patients with photosensitivity and debilitating diseases. Another analog named melanotan II and its derivative bremelanotide are being investigated for aphrodisiac effects.

Functions of melanotropin

The primary function of melanocyte-stimulating hormone is in stimulating the pigment cells to produce melanin. In lower animals like claw-toed frog, melanotropin makes the pigments in the skin to disperse and cause the skin to appear darker in dim light. The pigments are known as melanophores and the melanotropin is termed melanophore-stimulating hormone.

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These melanotropin peptides have anti-inflammatory properties. They also modulate the immune system. Melanotropin peptides are also found to regulate melatonin and endorphins production. Melanotropin synthetic analogs have different functions like reducing the appetite and aphrodisiac effects.

Conditions caused by increased melanotropin activity

The activity of the stimulating hormone increases in pregnant women. Combined with increased estrogens, most often, melanotropin causes hyperpigmentation in pregnant women. Oral contraceptive pills intake may also give similar results in some individuals. Increased activity of the melanocyte stimulating hormone can cause moles, tan and freckles. Administration of melanotropin can cause skin darkening even without sun exposure. In Addison’s disease and Cushing’s syndrome, there is increased release of adrenocorticotropic hormone. ACTH breaks down into melanotropin and causes hyperpigmentation.

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Tan development goes through the following sequence of events. When the keratinocyte cells in the basal layer of epidermal skin are exposed to ultraviolet radiation, the transcription factor p53 (the tumor-suppressor protein) is activated. p53 activates the POMC promoter. POMC cleaves to form the melanotropin. Melanocortin-1-receptor (MC1R) is expressed in melanocytes and is activated by melanotropin. By a biosynthetic cascade of reactions the melanin pigment is produced inside the melanosomes.

Melanocyte-stimulating hormone is found to complement leptin in regulating food intake, metabolism and body weight. Increase in melanotropin activity causes anorexia and decrease in bodyweight. Melanocyte-stimulating hormone deficiency can cause hypopigmentation, risk of sunburn and DNA damage, inflammatory diseases, body pain, thirst, frequent urination, sleeping problems, increased food intake, obesity and type 2 diabetes mellitus.

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Reference: 1.Hunt G, Todd C, Cresswell JE, Thody AJ. Alpha-melanocyte stimulating hormone and its analogue Nle4DPhe7 alpha-MSH affect morphology, tyrosinase activity and melanogenesis in cultured human melanocytes. J Cell Sci. 1994 Jan;107 ( Pt 1):205-11. 2.Valverde P, Healy E, Jackson I, Rees JL, Thody AJ. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat Genet. 1995 Nov;11(3):328-30. 3.Costa JL1, Hochgeschwender U, Brennan M. The role of melanocyte-stimulating hormone in insulin resistance and type 2 diabetes mellitus. Treat Endocrinol. 2006;5(1):7-13.

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