Question 1

What is Alpha-MSH?

Accepted Answer

Alpha-melanocyte-stimulating hormone (α-MSH) is a 13-amino acid neuropeptide derived from proopiomelanocortin (POMC) that serves as the endogenous agonist for melanocortin receptors MC1R-MC5R. It is a master regulator of pigmentation, inflammation, energy homeostasis, and sexual function. α-MSH stimulates melanin production through MC1R, suppresses appetite through MC4R, reduces inflammation through MC1R/MC3R, and modulates immune function. α-MSH is the parent compound from which therapeutic analogs (Melanotan I/afamelanotide, Melanotan II, PT-141/bremelanotide, setmelanotide) have been developed. The C-terminal tripeptide KPV retains potent anti-inflammatory activity. α-MSH's pleiotropic effects through the melanocortin system make it a template for drug development across dermatology, metabolic disease, inflammation, and sexual dysfunction.

Question 2

How does Alpha-MSH work?

Accepted Answer

α-MSH activates melanocortin receptors (MC1R-MC5R), all Gs-coupled GPCRs that increase cAMP. MC1R on melanocytes drives eumelanin synthesis through MITF-mediated tyrosinase expression. MC4R in hypothalamus suppresses appetite through POMC neuron activation. MC1R/MC3R on immune cells suppress NF-κB and reduce pro-inflammatory cytokines. MC4R in PVN stimulates sexual arousal through oxytocin and dopamine pathways.

Question 3

What are the research applications of Alpha-MSH?

Accepted Answer

Pigmentation Disorders

Afamelanotide (Melanotan I, Scenesse) is approved for erythropoietic protoporphyria.

Anti-Inflammatory Research

α-MSH and analogs reduce inflammation in models of IBD, arthritis, and neuroinflammation.

Obesity

Setmelanotide (MC4R agonist) is approved for genetic obesity from POMC/LEPR/PCSK1 deficiency.

Sexual Dysfunction

Bremelanotide (PT-141) approved for HSDD.

Question 4

What are the biological pathways affected by Alpha-MSH?

Accepted Answer

MC1R/cAMP/MITF/tyrosinase for melanogenesis. MC4R/POMC/α-MSH for appetite regulation. MC1R/NF-κB inhibition for anti-inflammation. MC4R/oxytocin/dopamine for sexual function.

Question 5

What are the potential side effects of Alpha-MSH?

Accepted Answer

Nausea, facial flushing, skin darkening (via MC1R), appetite changes. Effects depend on receptor selectivity of the specific analog used.

Question 6

How should Alpha-MSH be stored?

Accepted Answer

α-MSH has a short half-life (~minutes) in vivo due to rapid enzymatic degradation. The methionine residue is oxidation-prone. Synthetic analogs with D-amino acid substitutions and cyclization provide enhanced stability for therapeutic use.

Question 7

What is the regulatory status of Alpha-MSH?

Accepted Answer

Native α-MSH is an endogenous hormone. Therapeutic analogs are separately regulated: afamelanotide (EMA-approved), setmelanotide (FDA-approved), bremelanotide (FDA-approved).

Question 8

Where can I find research studies on Alpha-MSH?

Accepted Answer

Scientific studies on Alpha-MSH can be found in peer-reviewed journals through databases like PubMed and Google Scholar.

Question 9

What quality standards should Alpha-MSH meet for research?

Accepted Answer

Research-grade Alpha-MSH should meet high purity standards, typically >95% purity, with proper analytical certification and storage requirements.

Alpha-MSH