Alpha-MSH
Also known as: α-MSH, Alpha-melanocyte-stimulating hormone, POMC(138-150)
Evidence: Preclinical
Overview
Endogenous 13-residue POMC peptide that activates MC1, MC3, MC4 and MC5 receptors; injected, it changed human skin colour in a small 1961 study. Other effects are from animal models.
Alpha-MSH is residues 138 to 150 of proopiomelanocortin (POMC), N-terminally acetylated and C-terminally amidated, made in the pituitary, brain and skin. Injected alpha- and beta-MSH changed skin colour in volunteers in 1961, and a single 2.5 mg IV dose altered LH secretion in 8 women in 1994; no therapeutic trial of the native peptide has been published. Serum enzymes degrade it, which is why stabilized analogs were made: afamelanotide (Melanotan 1, an approved implant for erythropoietic protoporphyria), Melanotan II and bremelanotide (PT-141) are separate catalog entries, as is its C-terminal tripeptide KPV. Anti-inflammatory and appetite effects come from animal and cell models.
Benefits
Skin darkening (small uncontrolled human study, 1961), reduced food intake via MC4R (mouse genetics), anti-inflammatory effects (animal and cell models)
Dosing reference
- Research dose
- 50 to 200 mcg daily: vendor/community range, no published human dose. The only modern human dosing was a single 2.5 mg IV bolus
- Range
- 50 to 200 mcg, 1x daily
No dosing study exists. The one modern human exposure was a single 2.5 mg IV bolus in 8 women for endocrine research. The route, frequency and cycle used by vendors have no published basis.
Mechanism
Alpha-MSH is cleaved from POMC and acts on melanocortin receptors, a G protein-coupled family first cloned in 1992 alongside the separate ACTH receptor (Mountjoy et al., 1992). MC1R on melanocytes drives eumelanin synthesis. Central MC4R controls feeding: mice lacking MC4R develop obesity with hyperphagia (Huszar et al., 1997). Anti-inflammatory actions include reduced NF-kB activation and pro-inflammatory cytokines and increased IL-10, shown in cell and animal models of dermatitis, colitis, arthritis and fever (Brzoska et al., 2008). Native alpha-MSH is degraded by serum enzymes, and N-terminal acetylation slows its clearance in rabbits (Rudman et al., 1983).
Evidence
Preclinical: animal or in vitro data only
- Injected alpha- and beta-MSH changed skin colour in human volunteers in an uncontrolled study (Lerner and McGuire, 1961)
- Cloning of the human and mouse MSH receptor and the human ACTH receptor defined the melanocortin receptor family (Mountjoy et al., 1992)
- Targeted deletion of MC4R caused maturity-onset obesity with hyperphagia, hyperinsulinemia and hyperglycemia in mice (Huszar et al., 1997)
- Anti-inflammatory effects in animal models of fever, contact dermatitis, colitis, arthritis and organ injury (Brzoska et al., 2008)
- A single 2.5 mg IV bolus in 8 women in the luteal phase raised LH and blunted CRH suppression of LH, without changing ACTH or cortisol (Limone et al., 1994)
- Human-trial status: no therapeutic trial of native alpha-MSH has been published. Human efficacy data belong to stabilized analogs, chiefly afamelanotide (approved implant, EU 2014, US 2019) and bremelanotide (approved 2019); see those entries
References
- Effect of alpha- and beta-melanocyte stimulating hormones on the skin colour of man. Lerner AB, McGuire JS, Nature, 1961
- The cloning of a family of genes that encode the melanocortin receptors. Mountjoy KG, Robbins LS, Mortrud MT, et al., Science, 1992
- Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Huszar D, Lynch CA, Fairchild-Huntress V, et al., Cell, 1997
- Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Brzoska T, Luger TA, Maaser C, et al., Endocrine Reviews, 2008
- Three types of alpha-melanocyte-stimulating hormone: bioactivities and half-lives. Rudman D, Hollins BM, Kutner MH, et al., The American Journal of Physiology, 1983
- 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Sawyer TK, Sanfilippo PJ, Hruby VJ, et al., Proceedings of the National Academy of Sciences of the United States of America, 1980
- Alpha-melanocyte-stimulating hormone antagonizes the inhibitory effect of corticotropin-releasing hormone on luteinizing hormone secretion during the luteal phase in normal women. Limone P, Scipioni T, Calvelli P, et al., The Journal of Clinical Endocrinology and Metabolism, 1994
Side effects
No human safety study of repeated dosing exists. Skin colour change was the effect reported after injection in 1961 (Lerner and McGuire, 1961); the 1994 single IV dose study reported endocrine changes only (Limone et al., 1994). Nausea, flushing and darkening of moles are seen with the analogs and are plausible but not measured for native alpha-MSH. Commonly reported (anecdotal): nausea, flushing.
Storage
- Storage
- Room temperature, away from light
- Lyophilized
- 2 years at room temp
- Reconstituted
- N/A (ready to use)
Pharmacology
- Half-life
- Not measured in humans. In rabbit plasma (in vitro and IV) desacetyl alpha-MSH cleared fastest and diacetyl slowest; native peptide is degraded by serum enzymes
- Bioavailability
- Not measured by any route in any species. Native alpha-MSH is degraded by serum enzymes, unlike its [Nle4,D-Phe7] analog
- Molecular weight
- 1664.9 Da
- Sequence
- [Ac-S]YSMEHFRWGKPV[NH2]