Cortistatin
The cortical peptide that copies somatostatin's hormone effects and adds some of its own
Cortistatin was found in the brain cortex as a peptide that looks much like somatostatin and binds the same five receptors. Infused into volunteers, the human 17-residue form lowered growth hormone and insulin exactly as somatostatin did. What makes it interesting is the rest: it also binds the ghrelin receptor, human immune cells make it rather than somatostatin, and in mice it protects against sepsis, colitis and arthritis. It is approved nowhere and has only ever been given as a short research infusion.
Used in human trials: 2.0 mcg/kg/h, Continuous infusion, Intravenous (Study: healthy men, human cortistatin-17 against somatostatin-14) 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?
Cortistatin is a small cyclic peptide first described in the cerebral cortex, named for where it was found and for its likeness to somatostatin. The two share most of the ring that binds the receptor, and cortistatin binds all five somatostatin receptors with similar strength. In people the precursor yields a 17-residue peptide and a longer 29-residue one; rodents make a 14-residue form whose sequence is not identical to the human peptide.
On hormones it does what somatostatin does. In healthy volunteers, in people with acromegaly or a prolactinoma, and in patients with Cushing's disease, two-hour infusions of human cortistatin-17 lowered growth hormone, prolactin where it was high, and insulin to the same extent as somatostatin-14. In the Cushing's group both peptides lowered cortisol, and about half the patients showed a clear fall in ACTH as well. Nothing in these studies separates the two peptides at the pituitary or the pancreas.
The differences lie elsewhere. Cortistatin, unlike somatostatin, binds the ghrelin receptor and a second receptor called MrgX2, and the two peptides are made in different places. In human lymphoid tissue and blood cells it is cortistatin, not somatostatin, that is expressed, and its production rises as monocytes mature and after bacterial endotoxin. That led to a run of animal studies in which cortistatin reduced deaths from endotoxaemia and sepsis models, eased induced colitis and arthritis, and raised the pain threshold in rats. In rats it also deepened slow-wave sleep, and its precursor messenger RNA rose four-fold after a day without sleep.
Human studies outside the infusion work have only measured it. Plasma cortistatin was lower in people newly diagnosed with type 2 diabetes and tracked their glucose, insulin and HbA1c in the expected direction, and it was lower in people with hypertension, especially when blood pressure was uncontrolled. These are associations in small groups and say nothing about cause.
No regulator has approved cortistatin, and the human studies are short infusions in six to a dozen people at a time. The therapeutic claims made for it, in sepsis, bowel disease, arthritis and pain, all rest on rodent models.
Mechanism of Action
Cortistatin acts on the somatostatin receptors, which explains its hormone effects, and on two receptors somatostatin does not touch, which is the current explanation for the rest.
Somatostatin receptors
It binds all five, lowering growth hormone, prolactin where raised, and insulin in people just as somatostatin does.
Ghrelin receptor and MrgX2
Cortistatin also binds GHS-R1a and MrgX2; somatostatin binds neither, which is offered as the reason their effects differ.
Immune cells
Human lymphoid tissue and blood cells express cortistatin rather than somatostatin, and production rises with endotoxin.
Sleep and pain in rodents
Given into rat brain ventricles it deepens slow-wave sleep and raises the pain threshold; its precursor rises after sleep deprivation.
Published Research
These are studies of cortistatin read from their PubMed abstracts: the human infusion studies in volunteers and in pituitary disease, the work on where it is made in human tissue and immune cells, rodent studies of inflammation, pain and sleep, two studies measuring it in blood, and two reviews. Two earlier human infusions used the rat 14-residue peptide, a different molecule, and are listed under References instead of carded.
The human peptide is identified and tested
A human gene resembling rat cortistatin predicted mature peptides of 29 and 17 residues. Synthetic human cortistatin-17 bound all five human somatostatin receptors much as the rat 14-residue form does and lowered cAMP through them; given into rat brain ventricles it flattened cortical and hippocampal EEG.
The human 17-residue form behaves the same
Six healthy men received human cortistatin-17, rat cortistatin-14 and somatostatin-14 on separate days. All three lowered growth hormone and insulin to the same extent and blunted the growth hormone responses to GHRH and ghrelin equally, while prolactin, ACTH and cortisol were unaffected. The authors concluded that cortistatin's endocrine effects run through the classical somatostatin receptors.
Same effects in pituitary tumour patients
In patients with acromegaly or a prolactinoma and in healthy controls, cortistatin-17 and somatostatin-14 lowered growth hormone equally in acromegaly and in controls, lowered prolactin in prolactinoma, and lowered insulin in every group by the same amount.
Partial effect on ACTH in Cushing's disease
In nine patients with Cushing's disease, two-hour infusions of cortistatin-17 or somatostatin-14 both lowered cortisol, and five of the nine showed a clear fall in both ACTH and cortisol. Only the cortistatin arm reached statistical significance for ACTH; growth hormone did not change and insulin fell with both peptides.
Immune cells make cortistatin, not somatostatin
Across human lymphoid tissues and immune cells, cortistatin messenger RNA was widespread while somatostatin was found only in thymus tissue. Cortistatin rose as monocytes matured into macrophages and dendritic cells and after bacterial endotoxin, and it displaced an octreotide tracer from thymus tissue, which led the authors to propose cortistatin rather than somatostatin as the natural ligand in the human immune system.
Where cortistatin and MrgX2 sit in human tissue
In 56 non-tumour and 108 tumour samples, cortistatin protein was found in some gut, pancreatic, parathyroid and pituitary cells and patchily in neuroendocrine tumours, despite widespread messenger RNA. Protein for its specific receptor MrgX2 appeared only in the neurohypophysis and testis among the tissues tested.
Protects mice from lethal endotoxaemia
Cortistatin reduced inflammatory mediators from endotoxin-activated macrophages and, given to mice, cut deaths after bowel perforation or injection of endotoxin or E. coli, with less organ damage. The effect came with lower local and systemic levels of a wide range of cytokines, chemokines and acute phase proteins.
Eases experimental colitis
In mice with induced colitis, cortistatin reduced weight loss, diarrhoea and bowel inflammation and improved survival, including when treatment started after the disease was established. The authors tied the effect to a damped inflammatory and T helper 1 response and partly to regulatory T cells making interleukin-10.
Reduces collagen-induced arthritis
Given after arthritis had begun in mice, cortistatin lessened joint swelling and protected cartilage and bone, lowered inflammatory cytokines and chemokines, reduced the collagen-specific T cell response and raised interleukin-10 and TGF-beta. It acted on joint lining cells through both somatostatin and ghrelin receptors.
Raises the pain threshold in rats
Cortistatin injected into the brain ventricles of rats raised the threshold at which a painful stimulus produced a defensive response, which the authors took as evidence that it takes part in the system regulating pain perception.
Deepens slow-wave sleep
Cortistatin-14 given into rat brain ventricles increased deep slow-wave sleep and slow-wave activity in both light and dark periods. Precursor messenger RNA cycled over the day and was four times higher after 24 hours of sleep deprivation, falling back after eight hours of recovery sleep.
Lower blood cortistatin in new type 2 diabetes
In 60 people with newly diagnosed type 2 diabetes and 38 matched controls, plasma cortistatin measured by immunoassay was substantially lower in the patients. It correlated positively with HDL cholesterol and negatively with fasting glucose, insulin, insulin resistance and HbA1c.
Lower blood cortistatin in hypertension
Among 81 people with essential hypertension and 75 people with normal blood pressure, plasma cortistatin was lower in the hypertensive group and lower still in those whose blood pressure was uncontrolled. It fell as systolic pressure and serum creatinine rose, and the association held after adjustment.
A distinct regulator, not a copy of somatostatin
This review gathers the cell-culture, animal and knockout-mouse work on cortistatin's effects on growth hormone, prolactin and ACTH. Both peptides bind the five somatostatin receptors similarly, but they differ on truncated receptor variants, and only cortistatin binds the ghrelin receptor and MrgX2, which with their different tissue distribution is offered as the reason their effects are not identical.
Cortistatin as an immune signal
This review argues that cortistatin helps maintain immune tolerance in two ways: by shifting the balance between inflammatory and anti-inflammatory factors, and by encouraging regulatory T cells that suppress self-reactive effector cells. The evidence it reviews is from animal models of immune disease.
Dosing Data
Cortistatin is approved nowhere. These are the infusion rates used in published human studies of the human 17-residue peptide, 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 Cortistatin 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 Cortistatin, 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 Cortistatin stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Continuous infusion; Study: healthy men, human cortistatin-17 against somatostatin-14).
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 men, human cortistatin-17 against somatostatin-14: 120 minutes; Study: acromegaly, prolactinoma and healthy controls: 120 minutes; Study: Cushing's disease, nine patients: 120 minutes.
When effects appear: unknown; no source on this page gives a time to effect for Cortistatin. 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: Insulin fell during every infusion and rebounded at the end of the infusion in the Cushing's disease study (PMID 17893252); No safety data beyond single infusions of two hours in groups of six to a dozen people; Nothing is known about repeated dosing, any other route, or long-term use. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Cortistatin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the short infusion studies above, which reported little on safety”).
Interactions
- GHRH: an infusion of human cortistatin-17 blunted the growth hormone response to GHRH, as somatostatin-14 did
- ghrelin: cortistatin-17 blunted ghrelin's growth hormone response and abolished ghrelin's inhibition of insulin
Every peptide's record, with its source: the interaction matrix.
Source: human study, PMID 15336231.
Checking what you bought
Unknown: no published independent test of Cortistatin 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 Cortistatin's expected mass, 2,151.5 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 short infusion studies above, which reported little on safety.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Cortistatin is a research peptide; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is cortistatin?
A cyclic neuropeptide closely related to somatostatin, first found in the brain cortex. People make a 17-residue and a 29-residue form from the CORT gene.
?How is it different from somatostatin?
On hormone release in people it is not: infusions lowered growth hormone and insulin by the same amount. It differs in binding the ghrelin receptor and MrgX2, and in being the form that human immune cells make.
?Has cortistatin been given to people?
Yes, but only as two-hour intravenous infusions in small research studies of volunteers and of patients with acromegaly, prolactinoma or Cushing's disease.
?Is it a treatment for inflammation?
Not in people. The sepsis, colitis, arthritis and pain results are all from mice and rats; no human trial of cortistatin in an inflammatory disease was found.
?Does cortistatin affect sleep?
In rats, injected into the brain, it increased deep slow-wave sleep, and its precursor rose after sleep deprivation. There is no human sleep study here.
?Why do some papers about cortistatin concern cancer chemistry?
Because cortistatin A, a steroid alkaloid from a marine sponge, shares the name. It is an unrelated molecule.
?Can you buy cortistatin?
There is no approved product. Anything sold under the name sits outside a regulated supply, with no check on identity or amount.
References
- [other] UniProt O00230 (CORT_HUMAN): cortistatin-29 = residues 77-105, cortistatin-17 = 89-105, cortistatin-14 = 92-105, one disulfide bond; read October 30, 2026. Formula and mass computed for cortistatin-17 with that disulfide. https://www.uniprot.org/uniprotkb/O00230/entry
- [pubmed] Fukusumi S, et al. "Identification and characterization of a novel human cortistatin-like peptide." Biochem Biophys Res Commun, 1997;232(1):157-63. PMID: 9125122.
- [clinical-trial] Gottero C, et al. "Cortistatin-17 and -14 exert the same endocrine activities as somatostatin in humans." Growth Horm IGF Res, 2004;14(5):382-7. PMID: 15336231.
- [clinical-trial] Grottoli S, et al. "Cortistatin-17 and somatostatin-14 display the same effects on growth hormone, prolactin, and insulin secretion in patients with acromegaly or prolactinoma." J Clin Endocrinol Metab, 2006;91(4):1595-9. PMID: 16449338.
- [clinical-trial] Giordano R, et al. "The activation of somatostatinergic receptors by either somatostatin-14 or cortistatin-17 often inhibits ACTH hypersecretion in patients with Cushing's disease." Eur J Endocrinol, 2007;157(4):393-8. PMID: 17893252.
- [pubmed] Dalm VA, et al. "Cortistatin rather than somatostatin as a potential endogenous ligand for somatostatin receptors in the human immune system." J Clin Endocrinol Metab, 2003;88(1):270-6. PMID: 12519865.
- [pubmed] Allia E, et al. "Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours." J Pathol, 2005;207(3):336-45. PMID: 16161007.
- [pubmed] Gonzalez-Rey E, et al. "Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia." J Exp Med, 2006;203(3):563-71. PMID: 16492802.
- [pubmed] Gonzalez-Rey E, et al. "Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease." Proc Natl Acad Sci U S A, 2006;103(11):4228-33. PMID: 16537513.
- [pubmed] Gonzalez-Rey E, et al. "Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses." Ann Rheum Dis, 2007;66(5):582-8. PMID: 17151007.
- [pubmed] Méndez-Díaz M, et al. "Cortistatin, a modulatory peptide of sleep and memory, induces analgesia in rats." Neurosci Lett, 2004;354(3):242-4. PMID: 14700741.
- [pubmed] Bourgin P, et al. "Cortistatin promotes and negatively correlates with slow-wave sleep." Eur J Neurosci, 2007;26(3):729-38. PMID: 17686045.
- [pubmed] Chen W, et al. "Circulating levels of cortistatin are correlated with metabolic parameters in patients with newly diagnosed type 2 diabetes mellitus." Peptides, 2017;94:86-90. PMID: 28526556.
- [pubmed] Chen W, et al. "Reduced plasma cortistatin is related to clinical parameters in patients with essential hypertension." Peptides, 2024;177:171225. PMID: 38642617.
- [review] Ibáñez-Costa A, et al. "Cortistatin: A new link between the growth hormone/prolactin axis, stress, and metabolism." Growth Horm IGF Res, 2017;33:23-27. PMID: 28157571.
- [review] Gonzalez-Rey E, et al. "Emergence of cortistatin as a new immunomodulatory factor with therapeutic potential in immune disorders." Mol Cell Endocrinol, 2008;286(1-2):135-40. PMID: 17850953.
- [clinical-trial] Broglio F, et al. "Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans." J Clin Endocrinol Metab, 2002;87(8):3783-90. PMID: 12161511.
- [clinical-trial] Benso A, et al. "Effects of cortistatin-14 and somatostatin-14 on the endocrine response to hexarelin in humans." J Endocrinol Invest, 2003;26(7):599-603. PMID: 14594107.
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.
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