Alpha-MSH

Where it comes from

Made in

POMC neurons of the arcuate nucleus and brainstem; keratinocytes and melanocytes of the skin; the pituitary’s intermediate lobe, which adults barely have

Sent out by

In the brain, leptin and feeding; in the skin, ultraviolet light through p53

Acts on

• Melanocytes (eumelanin)
• Hypothalamic MC4R neurons (satiety)
• Immune cells
• Sebaceous glands

What it does

• Turns on dark pigment after sun exposure
• The brain’s signal of fullness; loss of POMC, or of MC4R, causes severe early obesity
• Calms inflammation and fever

In medicine

• Afamelanotide, an alpha-MSH analogue implant, is approved for erythropoietic protoporphyria, where pigment shields against painful light reactions ¹
• Setmelanotide (2020), an MC4R agonist, treats obesity from POMC, PCSK1 and LEPR deficiency, Bardet-Biedl syndrome (since 2022) and, since 2026, acquired hypothalamic obesity ⁴
• Bremelanotide (2019), another melanocortin analogue, is approved for low sexual desire in premenopausal women

Beyond the body’s own use

• Afamelanotide was tested in two randomised trials of 74 and 94 patients; in the American one, median pain-free time in sunlight over six months was 69 hours against 41 on placebo ¹
• Setmelanotide was approved on single-arm phase 3 trials: eight of ten patients with POMC deficiency and five of eleven with LEPR deficiency lost at least a tenth of their weight in a year, and hunger scores fell ²
• Melanotan II, an unapproved analogue injected for tanning, is linked in case reports to new and darkening moles, and four published reports describe a melanoma arising in a mole during or soon after use ³
• Health authorities in several countries have issued safety warnings about melanotan I and II; the preparations involved are unapproved and are not reviewed for safety, effectiveness or quality, so neither purity nor dose is known ³