Melanocyte-stimulating hormone beta
The POMC-derived melanocortin peptide that rodents lack, tied to human appetite and body weight through its MC4R action
Beta-MSH is one of the melanocortin peptides the body cuts from the large pro-opiomelanocortin protein. Humans make it; rodents, the usual laboratory animal, do not, which left it in the shadow of its better-known relative alpha-MSH for years. Human genetics brought it forward: a rare change in its sequence turned up in children with severe early-onset obesity and weakened its grip on the MC4R receptor, the appetite receptor. Beta-MSH itself is not a medicine; the drugs built on this pathway are separate molecules.
No established human dose Details ↓
Recommended Dosing
No established human dose
Beta-MSH is studied in people through genetics and measurement, not by giving it: the human studies here screen for variants in its sequence, measure it in cerebrospinal fluid, or define its true human form. The feeding and anti-inflammatory effects come from injecting it into the brains of animals or from cell assays, not from any human treatment.
What is it?
Beta-MSH is a melanocortin: one of a set of short peptides, along with alpha-MSH, gamma-MSH and ACTH, that the body cuts from a single large precursor called pro-opiomelanocortin. In humans it is released from beta-lipotropin, a larger fragment of that precursor, and carries the His-Phe-Arg-Trp core that all the melanocortins share and use to activate their receptors. It was first identified in pituitary extracts in the late 1950s, and its exact human form was debated for decades, with some arguing that a shorter 18-residue version is the true product in human tissues outside the pituitary.
What sets beta-MSH apart is a quirk of biology: rodents do not make it. Because mice and rats, the usual models of appetite research, produce only alpha-MSH from their pro-opiomelanocortin, most melanocortin work focused on alpha-MSH, and beta-MSH's role in people went unexamined. That changed when human genetics pointed straight at it.
In 2006 two groups reported the same finding. Screening 538 people with severe early-onset obesity, one group found five unrelated children carrying a rare missense variant in the beta-MSH sequence, Tyr221Cys, which was far more common than in the general population and tracked with obesity in their families. The variant peptide bound and activated the MC4R receptor poorly, and the children were hyperphagic and tall, both hallmarks of MC4R receptor deficiency. The second group described the same variant and reached the same conclusion from laboratory and brain studies: beta-MSH matters for human body-weight control.
Binding work supports the genetics. In cell and brain-slice assays, beta-MSH bound the MC4R receptor with higher affinity than alpha-MSH and activated the G-proteins in the hypothalamic nuclei that regulate feeding; food restriction raised beta-MSH in several of those nuclei while leaving alpha-MSH unchanged. These findings led some researchers to propose beta-MSH, not alpha-MSH, as the main MC4R signal in the regions that set appetite, though this remains debated.
Beta-MSH has other reported roles. It is anti-inflammatory in the brain through MC3R and MC4R receptors in animal models, and a recent human study found its level raised in the cerebrospinal fluid of people with painful restless legs syndrome. A dog carrying a natural pro-opiomelanocortin mutation that removes beta-MSH and beta-endorphin, but not alpha-MSH, is hungrier and burns less energy, echoing the human obesity link. The anti-obesity drugs built on the melanocortin pathway, such as setmelanotide, are separate molecules and are not covered here.
Mechanism of Action
Beta-MSH is cut from pro-opiomelanocortin and activates melanocortin receptors, chiefly MC4R in the hypothalamic nuclei that control appetite; rodents do not make it, so its biology is read mainly from humans and other species.
Appetite
It binds the MC4R receptor with high affinity; a variant that weakens that binding tracks with human obesity.
POMC processing
It is released from beta-lipotropin, one of several melanocortins from the same precursor.
Inflammation
In animal brain it is anti-inflammatory through MC3R and MC4R receptors.
Published Research
These are studies of beta-MSH itself, read from their PubMed abstracts: the human obesity-genetics studies, a human cerebrospinal-fluid study, work on its human form, binding and anti-inflammatory studies, a peptide-display study, and two reviews. Rodents do not make beta-MSH, so animal cards are labelled; studies whose subject is a melanocortin drug belong to that drug.
A variant in its sequence tracks with obesity
Screening 538 people with severe early-onset obesity found five unrelated children with the rare Tyr221Cys variant in the beta-MSH region, significantly more common than in the general population and co-segregating with obesity. The variant peptide bound and activated the MC4R receptor poorly, and carriers were hyperphagic with increased linear growth.
A second report of the same link
An independent group reported the same missense mutation in the beta-MSH coding region (Y5C) associated with early-onset obesity, and concluded from cell, animal and post-mortem human brain studies that beta-MSH plays a critical role in the hypothalamic control of human body weight.
The true human form of the peptide
Using two radioimmunoassays on human pituitary, hypothalamus and tumour extracts, the authors found that a shorter 18-residue peptide, not the classic 22-residue form once thought artefactual, is a normal product of pro-opiomelanocortin in human non-pituitary tissue.
Raised in painful restless legs syndrome
In 42 patients with restless legs syndrome and 44 controls, cerebrospinal fluid beta-MSH was significantly higher in those with painful restless legs than in non-painful cases or controls, and the ratio of melanocortins to beta-endorphin was highest in painful disease.
It activates a second receptor, GPR139
ACTH and alpha- and beta-MSH, and their shared His-Phe-Arg-Trp core, all activated the orphan receptor GPR139 in cells expressing the human receptor, showing beta-MSH signals beyond the classic melanocortin receptors.
Higher MC4R affinity than alpha-MSH
Beta-MSH bound the human MC4R receptor and rat hypothalamic MC4R receptors with higher affinity than alpha-MSH, activated G-proteins in the feeding-related hypothalamic nuclei, and rose there with food restriction while alpha-MSH did not, leading the authors to propose it as the key MC4R ligand for appetite.
Anti-inflammatory in the brain
In mice, beta-MSH suppressed bacterial-toxin-induced brain inflammation by blocking nuclear translocation of NF-kappaB and reducing nitric oxide production; an MC4R-preferring receptor antagonist blocked the effect, pointing to MC4R and possibly MC3R receptors.
A dog model without beta-MSH is hungrier
A common dog pro-opiomelanocortin mutation prevents production of beta-MSH and beta-endorphin but not alpha-MSH. Affected dogs had markedly lower energy expenditure and increased food-cue motivation; in cells, beta-MSH signalled at melanocortin receptors as well as alpha-MSH.
It suppresses feeding in chickens
Beta-MSH injected into the brain ventricles of chickens reduced food intake for 540 minutes and changed the expression of appetite-related genes in the hypothalamus, including corticotrophin-releasing factor and mesotocin, implicating those systems in its anorexigenic effect.
A display system maps its MC4R activity
A high-throughput cell-surface display platform screened over 2,000 single-residue variants of beta-MSH against an MC4R reporter, identifying positions that change receptor activation and a D5H mutant with enhanced activity, offering a route to designing melanocortin peptides.
Beta-MSH in the satiety pathway
A review of the authors' work on the melanocortin system in feeding and energy balance, setting out the case that beta-MSH is an endogenous MC4R ligand whose signalling changes with nutritional state.
Beta-MSH is poorly conserved across species
A historical review of melanotrophins notes that beta-MSH is much less conserved through evolution than alpha- or gamma-MSH and in some species is not even processed from beta-lipotropin, and cautions about assay cross-reactivity in measuring the melanocortins.
No Established Human Dose
Beta-MSH is studied in people through genetics and measurement, not by giving it: the human studies here screen for variants in its sequence, measure it in cerebrospinal fluid, or define its true human form. The feeding and anti-inflammatory effects come from injecting it into the brains of animals or from cell assays, not from any human treatment. There is no human preparation and no established human dose.
What this rests on: PMID 16459314, PMID 16459315, PMID 12732337.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Melanocyte-stimulating hormone beta is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Melanocyte-stimulating hormone beta has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Melanocyte-stimulating hormone beta, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Melanocyte-stimulating hormone beta stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Melanocyte-stimulating hormone beta. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Melanocyte-stimulating hormone beta lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: A loss-of-function variant in its sequence is associated with hyperphagia and early-onset obesity in people (PMID 16459314); In animals, brain injection suppressed feeding (PMID 32738351); loss of it in a dog model raised hunger and lowered energy use (PMID 38446876); No human safety data: it has not been administered to people in the sources read. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Melanocyte-stimulating hormone beta. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Beta-MSH is measured in people, not given, so there are no human adverse-event data”).
Interactions
Unknown: a PubMed search for human interaction studies of Melanocyte-stimulating hormone beta (reviewed 2026-10-30) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Melanocyte-stimulating hormone beta products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Melanocyte-stimulating hormone beta's expected mass, 2,204.4 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere in the sources read). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Beta-MSH is measured in people, not given, so there are no human adverse-event data. These notes come from the genetics and animal work above.
Contraindications & Cautions
No product label exists; the peptide is not given to people.
Legal Status
Beta-MSH is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is beta-MSH?
An 18-amino-acid melanocortin peptide cut from pro-opiomelanocortin, the same precursor that yields alpha-MSH and ACTH. It acts on melanocortin receptors, chiefly MC4R.
?Why do rodents not make it?
Mice and rats process their pro-opiomelanocortin to alpha-MSH but not beta-MSH, which is why beta-MSH's role was studied in humans and other species.
?How is beta-MSH linked to obesity?
A rare variant in its sequence, Tyr221Cys, was found in children with severe early-onset obesity; it binds the MC4R appetite receptor poorly and runs in affected families.
?Is it stronger than alpha-MSH?
At the MC4R receptor, beta-MSH bound with higher affinity than alpha-MSH in cell and brain assays, which is why some researchers see it as the key appetite signal there.
?Can you take beta-MSH?
No. There is no human preparation and no established human dose; in research it has been given only to animals or studied in cells.
?Is setmelanotide the same thing?
No. Setmelanotide is a melanocortin-receptor drug, a separate molecule; beta-MSH is one of the body's own melanocortins.
References
- [clinical-trial] Lee YS, et al. "A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance." Cell Metab, 2006;3(2):135-40. PMID: 16459314.
- [clinical-trial] Biebermann H, et al. "A role for beta-melanocyte-stimulating hormone in human body-weight regulation." Cell Metab, 2006;3(2):141-6. PMID: 16459315.
- [pubmed] Bertagna X, et al. "Human beta-melanocyte-stimulating hormone revisited." Proc Natl Acad Sci U S A, 1986;83(24):9719-23. PMID: 2432601.
- [clinical-trial] Koo BB, et al. "The Melanocortin and Endorphin Neuropeptides in Patients with Restless Legs Syndrome." Ann Neurol, 2024;95(4):688-699. PMID: 38308537.
- [pubmed] Nøhr AC, et al. "The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW." Neurochem Int, 2017;102:105-113. PMID: 27916541.
- [pubmed] Harrold JA, et al. "beta-MSH: a functional ligand that regulated energy homeostasis via hypothalamic MC4-R?." Peptides, 2003;24(3):397-405. PMID: 12732337.
- [pubmed] Muceniece R, et al. "Beta-MSH inhibits brain inflammation via MC(3)/(4) receptors and impaired NF-kappaB signaling." J Neuroimmunol, 2005;169(1-2):13-9. PMID: 16154641.
- [pubmed] Dittmann MT, et al. "Low resting metabolic rate and increased hunger due to β-MSH and β-endorphin deletion in a canine model." Sci Adv, 2024;10(10):eadj3823. PMID: 38446876.
- [pubmed] Cao C, et al. "The anorexigenic effect of beta-melanocyte-stimulating hormone involves corticotrophin-releasing factor and mesotocin in birds." Neurosci Lett, 2020;736:135282. PMID: 32738351.
- [pubmed] Lin A, et al. "A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor." Cell Genom, 2025;5(11):100988. PMID: 40930102.
- [review] Harrold JA, et al. "Melanocortin-4 receptors, beta-MSH and leptin: key elements in the satiety pathway." Peptides, 2006;27(2):365-71. PMID: 16290320.
- [review] Lowry P. "60 YEARS OF POMC: Purification and biological characterisation of melanotrophins and corticotrophins." J Mol Endocrinol, 2016;56(4):T1-T12. PMID: 26643914.
- [other] UniProt P01189 (COLI_HUMAN), pro-opiomelanocortin; residues 217-234 are beta-MSH (DEGPYRMEHFRWGSPPKD). Read October 30, 2026. https://www.uniprot.org/uniprotkb/P01189/entry
Sources & Citations
Every study on this page was read from its PubMed record on October 30, 2026. Regulatory status comes from Drugs@FDA (openFDA) and the EMA medicines list, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.