PHM-27
The second peptide on the VIP gene, and what infusing it did in people
The human gene for vasoactive intestinal peptide carries a second 27-residue peptide beside it, found when the precursor was cloned in 1983 and named PHM-27 for its terminal histidine and methionine. The two travel in the same nerves and do much the same things: relax smooth muscle, drive fluid into the gut, nudge pituitary hormones. In human studies PHM was usually the weaker of the pair. It is a research peptide, approved nowhere.
Used in human trials: 23 pmol/kg/min, Continuous infusion, Intravenous (Study: five patients with an ileostomy, ileal output) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
When the human precursor for vasoactive intestinal peptide was cloned in 1983, the sequence held a surprise: a second peptide of 27 amino acids sitting beside VIP. It was named PHM-27, for the histidine at one end and the amidated methionine at the other, and it turned out to be the human version of PHI-27, a peptide already found in pig intestine. Mapping the gene showed the two peptides encoded on adjacent exons, each with its own processing signals.
Because they come from one precursor, PHM and VIP are released together. They have been found side by side in nerves of the human gut, airways, penis, female genital tract and sweat glands, and both are poured out by VIP-producing tumours, where their plasma levels track each other. Messenger RNA for the shared precursor is highest in brain and pancreas.
In people PHM does VIP's work less strongly. Infused into patients with an ileostomy it raised ileal output more than tenfold, with watery, chloride-rich effluent, at plasma levels matching those seen in the watery diarrhoea syndrome caused by VIP-producing tumours. Given to healthy women it increased vaginal blood flow with the same maximum effect as VIP but roughly a tenth of its local potency. In strips of human airway, Fallopian tube, myometrium and erectile tissue it relaxed muscle, again generally weaker than VIP, and giving both together added nothing, which suggests they share a receptor.
At the pituitary the results are more interesting than useful. PHM raised prolactin in healthy volunteers but not in women with prolactin-secreting adenomas, and spinal-fluid PHM was low in people with prolactinoma and rose when their prolactin was treated, which led its investigators to propose it as a prolactin-releasing hormone. It did not change basal ACTH, but it amplified the ACTH response to corticotropin-releasing hormone, and in Cushing's disease a 100 microgram injection raised ACTH in a quarter of patients, fewer than VIP did.
No regulator has approved PHM-27 and nobody has tried it as a treatment. The human studies are small, mostly from the 1980s and early 1990s, and were designed to work out what the peptide does rather than to treat anything. Its longer relative PHV-42 and the porcine peptide PHI-27 are different molecules.
Mechanism of Action
PHM-27 is released with VIP from one precursor and appears to act at VIP's receptor, which is why its effects copy VIP's at lower potency.
One gene, two peptides
PHM-27 and VIP are encoded on adjacent exons of the same precursor and are released together from the same nerves and tumours.
Gut secretion
Infused into people it drove water and chloride into the ileum, raising output more than tenfold.
Smooth muscle relaxation
It relaxed human bronchi, Fallopian tube, myometrium and erectile tissue, usually less strongly than VIP, and the two were not additive.
Pituitary effects
It raised prolactin in healthy subjects, amplified the ACTH response to CRH, and raised ACTH in a minority of Cushing's patients.
Published Research
These are studies of PHM-27 read from their PubMed abstracts: the cloning and gene studies that found it, human infusion and injection studies of gut secretion, blood flow, prolactin, ACTH and growth hormone, measurements in tumours and in anorexia nervosa, and tissue studies of where it sits and what it relaxes. Studies of porcine PHI-27 are a different molecule and are not carded here.
Found inside the cloned VIP precursor
Cloning the DNA for the human VIP messenger RNA showed that the precursor protein holds not only VIP but a second peptide of 27 amino acids. The authors named it PHM-27; it differs by two residues from porcine PHI-27 and is closely related in sequence to VIP itself.
Two adjacent exons, one gene
Mapping the human gene showed PHM-27 and VIP encoded on two short, separate exons about 0.75 kilobases apart, each carrying the hormone's residues and its processing signals, with near-identical splice sites. The authors noted this arrangement would allow alternative processing of the messenger RNA.
In the nerves of the human penis
PHM-like immunoreactivity was found in human penile tissue by radioimmunoassay and staining, highest in the corpus cavernosum and vas deferens, and in the cavernosa it sat entirely in nerves around arteries. Chromatography matched synthetic PHM rather than the porcine peptide.
Released with VIP by VIP-producing tumours
In plasma from 39 patients with VIP-producing tumours, PHM measured with a C-terminal antibody tracked VIP closely, while N-terminal PHM values were higher and correlated poorly. Infusing PHM showed the excess was not explained by slower clearance or by breakdown to smaller fragments; a larger N-terminal form made up most of the signal.
A stronger bronchodilator than isoproterenol
In human bronchi taken at surgery, VIP, PHM and isoproterenol all relaxed the muscle, with VIP and PHM about fifty times more potent than isoproterenol; bronchioles relaxed to isoproterenol but not to either peptide. Propranolol and indomethacin did not block the peptides, pointing to a direct action on airway smooth muscle.
Amplifies the ACTH response to CRH
Given to people, synthetic PHM alone did not change basal ACTH or cortisol, but it strongly increased the ACTH release produced by corticotropin-releasing hormone. With earlier work showing PHM immunoreactivity in the human hypothalamus and pituitary stalk, the authors suggested a physiological role in ACTH control.
Turns the ileum into a secreting organ
Infused at 23 pmol/kg/min into five patients with an ileostomy, PHM raised plasma levels from about 22 to about 6,000 pM and increased ileal output from about 16 to about 177 grams per 30 minutes, with less solid material and more chloride. The plasma levels reached matched the highest seen in watery diarrhoea syndrome, which the authors said PHM may help cause.
Proposed as a prolactin-releasing hormone
The human hypothalamus contained about 19 pmol of PHM, similar to its content of GHRH or CRH, and PHM was measurable in cerebrospinal fluid. Spinal-fluid levels were lower in patients with prolactinomas, rose after bromocriptine corrected the high prolactin, and were low in pregnancy, with prolactin and spinal-fluid PHM inversely correlated. Intravenous PHM raised plasma prolactin, more in women than in men.
Relaxes tissue of the female reproductive tract
PHM and VIP were found together in nerve fibres of the human female genital tract, most densely in the vagina and cervix, where the PHM concentration was four times VIP's. Both peptides relaxed strips of Fallopian tube and myometrium in a dose-dependent way; given together their effect was additive and no greater than VIP alone, suggesting a shared receptor.
Raises vaginal blood flow, about a tenth as potently as VIP
Given to healthy women under the vaginal lining or intravenously, PHM increased vaginal blood flow in proportion to the dose, with flow tracking plasma PHM whichever route was used. Its maximum effect matched VIP's, but injected locally it was about ten times less potent.
In sweat glands and in sweat
Human axillary skin held both VIP and PHM immunoreactivity, with VIP about twice as abundant. Nerve fibres containing both ringed eccrine but not apocrine sweat glands, binding sites for each peptide sat on the secretory cells, and both peptides were measurable in collected sweat.
Exaggerated release after a meal in anorexia nervosa
In untreated patients with anorexia nervosa given a liquid meal, plasma PHM rose higher than in controls and peaked at 30 minutes, in the same pattern as their cholecystokinin, while VIP did not change in either group. Refeeding returned the cholecystokinin pattern to normal.
Weaker than VIP in erectile tissue
Human corpus cavernosum and circumflex vein both contained VIP and PHM in nerve fibres beside smooth muscle. Neither peptide did anything to resting tissue, but both relaxed preparations that had been contracted with noradrenaline; in the corpus cavernosum PHM's maximum relaxation was about 9% against VIP's 22%, while in the vein both were strong.
Where the shared gene is switched on
Northern blotting of ten normal human tissues found VIP and PHM-27 messenger RNA in brain, pancreas, colon, ileum and striated muscle, and none in liver, kidney, lung, heart, prostate or placenta. Brain and gut carried a single 1.7 kilobase transcript, while skeletal muscle showed a 7.0 kilobase one; brain and pancreas had the highest levels.
Raises ACTH in a quarter of Cushing's patients
Given as a 100 microgram intravenous bolus to 12 women with Cushing's disease and 8 healthy women, PHM raised ACTH and cortisol in 3 of the 12 patients and in none of the healthy subjects, against 5 of 12 for VIP and 9 of 12 for CRH. Every PHM responder also responded to VIP, and giving PHM with CRH produced additive rises.
Prolactin rises in healthy people, not in adenoma
Infused at 3.3 micrograms per minute for an hour, PHM-27 raised prolactin in six healthy subjects from about 7.8 to about 13 micrograms/l at 30 minutes but left prolactin unchanged in 11 women with prolactin-secreting adenomas. The infusion was well tolerated with no important adverse events.
A paradoxical growth hormone rise in some patients
In 22 patients with high prolactin, single 100 microgram injections of VIP and of PHM on separate days produced a paradoxical growth hormone rise of at least 50% in 13 patients after VIP and 4 after PHM. Three of the four PHM responders also responded to VIP, which the authors read as PHM acting weakly at the VIP receptor.
Dosing Data
PHM-27 is approved nowhere. These are the amounts given in published human studies, as stated in their abstracts; none was a treatment course.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or 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 PHM-27 is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intravenous). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store PHM-27, 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 PHM-27 stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Continuous infusion; Study: five patients with an ileostomy, ileal output).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: healthy subjects and hyperprolactinaemic women, prolactin: 60 minutes; Study: Cushing's disease and healthy women, ACTH: Single injection, sampling to 120 minutes; Study: patients with high prolactin, growth hormone: Single injection.
When effects appear: unknown; no source on this page gives a time to effect for PHM-27. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: The hour-long prolactin infusion was well tolerated with no important adverse events (PMID 7698720); Infusion raised ileal output more than tenfold with watery effluent, so fluid loss is the expected effect at those levels (PMID 3238051); No safety data beyond single infusions and injections in groups of five to twenty people. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping PHM-27. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the human studies above, which reported little on safety”).
Interactions
- corticotropin-releasing hormone: PHM alone did not change basal ACTH or cortisol but strongly increased the ACTH release produced by CRH in healthy people
- corticotropin-releasing hormone (Cushing's disease): giving PHM together with CRH produced additive rises in ACTH and cortisol in patients with Cushing's disease
Every peptide's record, with its source: the interaction matrix.
Source: human study, PMID 2824555; human study, PMID 8200939.
Checking what you bought
Unknown: no published independent test of PHM-27 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 PHM-27's expected mass, 2,985.4 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Approved nowhere 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
From the human studies above, which reported little on safety.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
PHM-27 is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is PHM-27?
A 27-amino-acid peptide encoded on the same gene as vasoactive intestinal peptide and released with it. The name comes from its histidine at one end and amidated methionine at the other.
?How is it related to VIP?
They sit on adjacent exons of one precursor, travel in the same nerve fibres and act at what appears to be the same receptor. In human studies PHM produced the same kinds of effects as VIP, usually at lower potency.
?What is PHI-27?
The pig version of the same peptide, differing by two residues. Studies of PHI are studies of a different molecule.
?Has PHM-27 been given to people?
Yes, in small research studies: intravenous infusions in patients with an ileostomy and in volunteers, local injection in the vagina, and single 100 microgram injections in pituitary disease.
?Does it affect prolactin?
It raised prolactin in healthy subjects but not in women with prolactin-secreting adenomas. Spinal-fluid levels were low in prolactinoma and rose when the high prolactin was treated, which is why it was proposed as a prolactin-releasing hormone.
?Why would a peptide cause diarrhoea?
Because like VIP it drives water and chloride secretion into the bowel. Infused into people with an ileostomy it raised output more than tenfold, at plasma levels matching those in VIP-producing tumours.
?Is there a PHM-27 product?
No. It is not approved anywhere, and anything sold under the name sits outside a regulated supply.
References
- [other] UniProt P01282 (VIP_HUMAN): intestinal peptide PHM-27 = residues 81-107 with a C-terminal methionine amide, vasoactive intestinal peptide = residues 125-152; read October 30, 2026. Formula and mass computed from the 27-residue sequence as the C-terminal amide. https://www.uniprot.org/uniprotkb/P01282/entry
- [pubmed] Itoh N, et al. "Human preprovasoactive intestinal polypeptide contains a novel PHI-27-like peptide, PHM-27." Nature, 1983;304(5926):547-9. PMID: 6571696.
- [pubmed] Bodner M, et al. "Coding sequences for vasoactive intestinal peptide and PHM-27 peptide are located on two adjacent exons in the human genome." Proc Natl Acad Sci U S A, 1985;82(11):3548-51. PMID: 2987932.
- [pubmed] Yiangou Y, et al. "Peptide histidine methionine (PHM) and the human male genitalia." Neuropeptides, 1985;6(2):133-42. PMID: 3889699.
- [pubmed] Fahrenkrug J, et al. "Cosecretion of peptide histidine methionine (PHM) and vasoactive intestinal peptide (VIP) in patients with VIP-producing tumors." Peptides, 1986;7(5):717-21. PMID: 3797338.
- [pubmed] Palmer JB, et al. "VIP and PHM and their role in nonadrenergic inhibitory responses in isolated human airways." J Appl Physiol (1985), 1986;61(4):1322-8. PMID: 3781947.
- [pubmed] Sasaki A, et al. "Potentiation of peptide histidine methionine (PHM) on corticotropin-releasing hormone (CRH) induced ACTH secretion in humans." J Clin Endocrinol Metab, 1987;65(6):1305-7. PMID: 2824555.
- [pubmed] Calam J, et al. "Peptide histidine methionine (PHM) increases ileostomy output." Regul Pept, 1988;23(1):57-62. PMID: 3238051.
- [pubmed] Sasaki A, et al. "Peptide histidine methionine may be a prolactin-releasing hormone in humans." J Clin Endocrinol Metab, 1988;66(6):1202-7. PMID: 3131380.
- [pubmed] Palle C, et al. "Peptide histidine methionine and vasoactive intestinal peptide: occurrence and relaxant effect in the human female reproductive tract." Biol Reprod, 1989;41(6):1103-11. PMID: 2624870.
- [pubmed] Palle C, et al. "Peptide histidine methionine (PHM) increases vaginal blood flow in normal women." Peptides, 1990;11(3):401-4. PMID: 2381867.
- [pubmed] Eedy DJ, et al. "Vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in human eccrine sweat glands: demonstration of innervation, specific binding sites and presence in secretions." Br J Dermatol, 1990;123(1):65-76. PMID: 2390496.
- [clinical-trial] Harty RF, et al. "Cholecystokinin, vasoactive intestinal peptide and peptide histidine methionine responses to feeding in anorexia nervosa." Regul Pept, 1991;36(1):141-50. PMID: 1796180.
- [pubmed] Kirkeby HJ, et al. "Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) in human penile corpus cavernosum tissue and circumflex veins: localization and in vitro effects." Eur J Clin Invest, 1992;22(1):24-30. PMID: 1348474.
- [pubmed] Schulte-Bockholt A, et al. "Gene expression and transcript size of the prepro-peptide VIP/PHM-27 in normal human tissue." Neurosci Lett, 1993;164(1-2):101-4. PMID: 8152582.
- [pubmed] Watanobe H, et al. "Stimulation by peptide histidine methionine (PHM) of adrenocorticotropin secretion in patients with Cushing's disease: a comparison with the effect of vasoactive intestinal peptide (VIP) and a study on the effect of combined administration of corticotropin-releasing hormone with PHM or VIP." J Clin Endocrinol Metab, 1994;78(6):1372-7. PMID: 8200939.
- [pubmed] Muratori M, et al. "Prolactin responsiveness to peptide histidine methionine-27 in normal subjects and hyperprolactinemic patients." Horm Res, 1994;42(6):257-61. PMID: 7698720.
- [clinical-trial] Watanobe H, et al. "Anomalous growth hormone response to vasoactive intestinal peptide and peptide histidine methionine in patients with prolactinoma or hypothalamic hyperprolactinemia." Neuropeptides, 1994;27(2):137-42. PMID: 7991068.
Sources & Citations
Every study on this page was read from its PubMed record on October 30, 2026. Status comes from Drugs@FDA (openFDA), 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.