Relaxin-3
The brain member of the relaxin family: made in one brainstem nucleus, studied for appetite, stress, arousal and memory in rodents, and only measured in people
Relaxin-3 is a two-chain peptide of the insulin and relaxin family that the brain makes in a small cluster of brainstem neurons, the nucleus incertus. Its own receptor, RXFP3, sits in brain areas that handle stress, arousal, memory and eating. Given into rat brains it makes them eat more, raises stress and reproductive hormones and shifts the hippocampal theta rhythm. In people it has only been measured, in blood, tissue and genes, and it has never been given to anyone.
No established human dose Details ↓
Recommended Dosing
No established human dose
Relaxin-3 has not been given to people in any study on this page. The human evidence is measurement only: blood levels compared between groups of women, children and young men, gene variants tested in patients and in UK Biobank, and the peptide located in post-mortem brain, testis and prostate.
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What is it?
Relaxin-3 is the newest of the human relaxins and the one that belongs to the brain. It was found in 2001 by searching the human genome for genes that looked like relaxin, and like insulin it is built from two short chains, an A chain of 24 amino acids and a B chain of 27, held together by three disulfide bonds. It is sometimes called INSL7 or insulin-like peptide 7. Its sequence has changed very little across mammals and lower vertebrates.
The name invites confusion with relaxin-2, the pregnancy hormone that was developed as the heart-failure drug serelaxin. The two share a family resemblance and relaxin-3 can activate the relaxin-2 receptor, RXFP1, in the laboratory, but they behave as different hormones. Relaxin-3 has its own receptor, RXFP3, which no other family member switches on, and the bulk of it is made inside the brain. In people with newly diagnosed diabetes the two moved independently: relaxin-2 was lower than in healthy people and relaxin-3 was unchanged.
Most relaxin-3 comes from one small cluster of GABA-releasing neurons in the floor of the brainstem, the nucleus incertus, with smaller groups nearby. Their fibres run forward to the septum, hippocampus, hypothalamus and thalamus, places that deal with alertness, memory, stress and appetite. The neurons carry receptors for CRF, the brain's main stress signal, and in rats stress or a CRF injection switches most of them on. A study of post-mortem human brains published in 2024 found the same nucleus in people, with relaxin-3 present across the hippocampus.
What relaxin-3 does has been worked out almost entirely in rats and mice. Injected into the brain it makes fed rats eat, and two weeks of infusion adds weight, more readily in females than in males. It raises stress hormones through hypothalamic CRH and vasopressin, raises luteinising hormone through GnRH, and in the septum it supports the hippocampal theta rhythm that goes with spatial memory. Knockout mice that cannot make it are surprisingly normal, with small changes in anxiety-like behaviour and less night-time wheel running, which fits the view of reviewers that relaxin-3 tunes arousal rather than switching any one behaviour on or off.
Human evidence is thin and consists only of measurements. Serum levels have been reported higher in women with metabolic syndrome and in children with autism, and lower in boys with delayed puberty, while plasma levels did not differ in diabetes. A gene study in antipsychotic-treated patients linked variants to weight and cholesterol problems, but a far larger UK Biobank analysis found no link between relaxin-3 system variants and depression, anxiety or metabolic syndrome. A 2021 systematic review found no high-quality clinical study at all.
Nobody has given relaxin-3 to a person in any study read for this page, and there is no relaxin-3 medicine. Drug researchers have instead built receptor-selective analogues and stapled mimetics; these are separate molecules, still in animal and laboratory testing. Anything sold online as relaxin-3 is outside any regulated supply.
Mechanism of Action
Relaxin-3 is released by brainstem neurons onto forebrain areas that carry its receptor, RXFP3. In rodents that signalling shifts eating, stress hormones, reproductive hormones and arousal; none of these actions has been tested in people.
Appetite
Brain injections or infusions make rats eat more and gain weight, with females more sensitive than males.
Stress axis
Its neurons respond to CRF and stress, and the peptide in turn releases CRH and vasopressin from the hypothalamus, raising ACTH and corticosterone in rats.
Arousal and memory
Through the medial septum it supports the hippocampal theta rhythm and spatial memory in rats; mice without it run less during their active phase.
Reproductive hormones
In male rats it raises luteinising hormone by releasing GnRH from the hypothalamus.
Published Research
These are studies of relaxin-3 and its gene, read from their PubMed abstracts: the papers that matched it to its receptors and made it synthetically, rat and mouse studies of appetite, stress, reproduction, memory and arousal, human tissue maps, five studies that measured it in human blood or genes, a test on human sperm, and two reviews. Every human study here measured relaxin-3; none gave it.
Found by fishing its receptor out of pig brain
Researchers searching for the natural partner of an orphan brain receptor, then called GPCR135 and now RXFP3, purified the active substance from pig brain and found it was the product of the relaxin-3 gene. Recombinant human relaxin-3 switched the receptor on at sub-nanomolar concentrations, no other insulin or relaxin family peptide did, and the gene was active mainly in a brainstem cluster known as the nucleus incertus.
A second receptor, mostly outside the brain
The same group showed that a related orphan receptor, GPCR142 (now RXFP4), also responded to relaxin-3 at nanomolar levels while ignoring every other family member. Its messenger RNA turned up in human kidney, testis, thymus, placenta, prostate, colon and several glands as well as brain, and no complete rat version of the receptor could be found.
Hard to make in the lab
Unlike relaxin-1 and relaxin-2, human relaxin-3 did not fold correctly when its two chains were simply mixed, so the authors built each chain separately and closed the three disulfide bonds one at a time. The synthetic peptide activated relaxin receptors in cells and, given to live animals, stimulated drinking through relaxin receptors in the brain, and structural work showed it is less tightly helical than the other two human relaxins.
Nucleus incertus neurons respond to stress
In rats, relaxin-3 was made chiefly by neurons of the nucleus incertus in the pons, stored in dense-cored vesicles and carried in fibres to the septum, hippocampus, lateral hypothalamus and thalamus. Nearly all of these neurons carried the CRF1 stress-hormone receptor; injecting CRF into the brain or restraining the rats in water activated most of them and raised relaxin-3 gene activity.
Rats eat more after a brain injection
Human relaxin-3 injected into the brain ventricles, or directly into the paraventricular nucleus of the hypothalamus, significantly increased what already-fed male rats ate over the next hour, early in both the light and the dark phase. Relaxin-2 given in the same molar amount had no such effect, which pointed to a receptor that relaxin-3 activates and relaxin-2 does not.
Two weeks of infusion added weight
Rats given relaxin-3 continuously into the brain by osmotic minipump for 14 days ate more and gained more weight than rats given the vehicle, without moving more or less. Their blood leptin and insulin were higher at the end, consistent with the extra fat they had laid down.
A push on the reproductive axis
Central injections of human relaxin-3 raised luteinising hormone in the blood of male rats within 30 minutes, and blocking GnRH outside the brain prevented the rise. In tissue it released GnRH from hypothalamic slices and a GnRH cell line but did not act on the pituitary directly, and relaxin-2 had no effect, so the authors place relaxin-3's reproductive action at the hypothalamus.
Theta rhythm and spatial memory
In rats, relaxin-3 signalling in the medial septum, the pacemaker for the hippocampal theta rhythm, changed septal and hippocampal firing and promoted theta activity. The peptide's own signalling in the septum supported spontaneous alternation in a maze, a simple spatial memory test, and nucleus incertus fibres were seen touching the septal neurons that drive the hippocampus.
Mice without the gene look almost normal
Knockout mice lacking relaxin-3 grew and weighed the same as their littermates and performed normally in tests of movement, pain, social contact, fear memory and depression-like behaviour. The differences were narrow: more entries into the open arms of an elevated maze, a sign of lower anxiety, and a stronger startle response to sudden noise.
Less running at night without relaxin-3
In relaxin-3 knockout mice backcrossed onto the C57BL/6J strain, a broad test battery again found no clear deficits in coordination, memory, anxiety or stress responses. Given running wheels in the home cage, though, the knockout mice ran much less during the dark phase, when mice are normally active, and spent more time still, which fits a role in arousal and the sleep-wake cycle.
Stress hormones rise through CRH
In male rats a brain injection of human relaxin-3 raised corticosterone within 30 minutes, and injections into the paraventricular nucleus raised ACTH and prolactin as well. Hypothalamic tissue exposed to relaxin-3 released corticotrophin-releasing hormone and vasopressin, while pituitary tissue did not respond, so its effect on the stress axis appears to start in the hypothalamus.
Female rats respond more strongly
Given into the brain at three doses, relaxin-3 increased short-term eating in female rats at the lowest dose and raised 24-hour weight gain at the highest, neither of which happened in males. Males instead showed the stronger stress response, with higher corticosterone and more CRF activity in the paraventricular nucleus, so the two sexes reacted along different lines.
Relaxin-3 given through the nose
Relaxin-3 sprayed into the nose of rats increased their food intake, which points to the nose as a possible route of delivery. The same study built a stapled, protease-resistant mimetic and tested it for anxiety- and depression-like behaviour; that compound is a different molecule, and its results belong to it rather than to relaxin-3.
Located in human brain, testis and prostate
Antibody staining of human and rhesus monkey tissue placed relaxin-3 in brainstem tegmental nuclei, in the space around the sperm-producing tubules of the testis and in the supporting stroma of the prostate. The rhesus form of the peptide, cloned for the study, protected cultured human nerve cells, an action not tested further in the abstract.
The human nucleus incertus, mapped for the first time
Post-mortem sections of the human pons revealed a cluster of GABA-making neurons containing relaxin-3 and the CRH type 1 receptor in the place where the nucleus incertus sits in other species. Relaxin-3 was also detected in hippocampal neurons that lack its messenger RNA, consistent with delivery from elsewhere, and in one Alzheimer's disease brain the relaxin-3 neurons carried abnormal tau.
Higher in women with metabolic syndrome
Among 300 women, the 150 with metabolic syndrome had higher serum relaxin-3 than the 150 healthy controls, and the level rose with each part of the syndrome: waist size, blood pressure, glucose and blood fats. The design shows an association at one point in time and cannot say whether relaxin-3 contributes to the syndrome or follows it.
No difference in newly diagnosed diabetes
In 33 people with newly found type 2 diabetes and 38 healthy people of similar age, plasma relaxin-3 did not differ between groups and did not track glucose, insulin, HbA1c, blood pressure or cholesterol. Relaxin-2, measured alongside, was lower in the diabetes group, which shows that the two hormones behave differently.
Lower in boys with delayed puberty
Thirty young males with delayed puberty had lower serum relaxin-3 than 30 matched controls, along with lower testosterone, LH and FSH and smaller testes. Across both groups relaxin-3 rose with age, Tanner stage, testis size and sex hormones and fell as body mass index went up.
Higher in children with autism
Serum relaxin-3 was higher in 50 children with autism spectrum disorder than in 30 controls. Within the autism group, higher levels went with lower listening-response scores, more speech problems and a stronger desire to drink, and with less fussy eating and weaker satiety responses.
Gene variants and weight gain on antipsychotics
Ten variants in the relaxin-3 gene and its two receptor genes were tested in 419 US patients taking antipsychotic drugs, a group at high risk of metabolic syndrome. Several variants were linked with obesity, diabetes or high cholesterol; the cohort was cross-sectional, with no replication group described.
UK Biobank finds no genetic link
Candidate variants in genes of the relaxin-3 system, chosen for likely effects on function, were tested against depression, atypical depression, anxiety and metabolic syndrome in UK Biobank samples of about 86,000 to 387,000 people. After correction for multiple testing none of the variants was associated with any outcome, alone or combined.
Sperm keep moving a little longer
Normal human semen samples incubated with relaxin-3 lost less of their motility over four hours, most clearly at the lowest concentration tested. The receptor protein RXFP3 was seen on the sperm head and neck, although its messenger RNA was absent, which suggests the protein is made earlier in sperm development.
The first ten years of relaxin-3 research
This review traces relaxin-3 from its discovery by a genome search in 2001 to its identification as a conserved neuropeptide made by GABA neurons of the brainstem. It describes the relaxin-3 network as an ascending arousal system that reaches the forebrain and may influence stress, memory, feeding, reward and sleep, and lists what was still unknown.
Depression and anxiety, systematically reviewed
A systematic search found 51 studies on relaxin-3 signalling and depression or anxiety. Animal work broadly supported a role in arousal and in reducing depressive- and anxiety-like behaviour, and pooled rat studies showed a strong appetite effect from acute receptor activation, but the authors found no high-quality clinical studies.
No Established Human Dose
Relaxin-3 has not been given to people in any study on this page. The human evidence is measurement only: blood levels compared between groups of women, children and young men, gene variants tested in patients and in UK Biobank, and the peptide located in post-mortem brain, testis and prostate. The only human material exposed to it was semen in a dish. There is no relaxin-3 medicine and no amount for a person to state.
What this rests on: PMID 23018057, PMID 37967073, PMID 39014514, PMID 29159832.
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 Relaxin-3 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 Relaxin-3 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 Relaxin-3, 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 Relaxin-3 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Relaxin-3. 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 Relaxin-3 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: Brain injections and infusions increased food intake and body weight in rats (PMIDs 15845619, 16777712); It raised the stress hormones ACTH and corticosterone in rats (PMID 24578294); It raised luteinising hormone in male rats, showing an action on the reproductive axis (PMID 18492777); No study read gave relaxin-3 to a person, so its human safety is unknown. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Relaxin-3. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Relaxin-3 has never been given to people, so it has no recorded human side effects”).
Interactions
Unknown: a PubMed search for human interaction studies of Relaxin-3 (reviewed 2026-11-03) 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 Relaxin-3 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 Relaxin-3's expected mass, 5,500.4 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: an endogenous neuropeptide studied in animals and measured in human blood). 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
Relaxin-3 has never been given to people, so it has no recorded human side effects. These are the effects seen in animals.
Contraindications & Cautions
There is no relaxin-3 medicine. These cautions concern the peptide as a research chemical and its blood tests.
Legal Status
Relaxin-3 is an endogenous neuropeptide studied in animals; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is relaxin-3?
A two-chain peptide of the insulin and relaxin family, also called INSL7, made mainly by a small group of neurons in the brainstem. It works mainly as a neuropeptide in the brain, although it is also measured in blood.
?Is relaxin-3 the same as relaxin or serelaxin?
No. Serelaxin is a copy of relaxin-2, the pregnancy hormone. Relaxin-3 is a separate gene and peptide with its own receptor, RXFP3, and the two behaved differently in people with diabetes.
?What does relaxin-3 do?
In rats and mice it affects eating, the stress-hormone response, reproductive hormones, the hippocampal theta rhythm and activity across the day. Reviewers describe it as part of an arousal system that reaches much of the forebrain.
?Does relaxin-3 cause weight gain?
Brain injections and two-week infusions made rats eat more and gain weight, especially females. Whether it does anything similar in people is unknown; women with metabolic syndrome had higher blood levels in one study, but no study has given it to a person.
?Is relaxin-3 linked to depression or anxiety?
Animal work suggests it can reduce anxiety- and depression-like behaviour, but the largest human study, a UK Biobank gene analysis, found no link between relaxin-3 system variants and depression, anxiety or metabolic syndrome.
?Can you take relaxin-3?
No. It has never been given to people in the studies read, there is no approved product, and no human dose exists.
References
- [other] UniProt Q8WXF3 (REL3_HUMAN), B chain = residues 26-52, A chain = residues 119-142, two interchain and one intrachain disulfide bond; read November 3, 2026. Formula and mass computed from the two chains with three disulfides. https://www.uniprot.org/uniprotkb/Q8WXF3/entry
- [pubmed] Liu C, et al. "Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135." J Biol Chem, 2003;278(50):50754-64. PMID: 14522968.
- [pubmed] Liu C, et al. "Identification of relaxin-3/INSL7 as a ligand for GPCR142." J Biol Chem, 2003;278(50):50765-70. PMID: 14522967.
- [pubmed] Tregear GW, et al. "The chemistry and biology of human relaxin-3." Ann N Y Acad Sci, 2005;1041:40-6. PMID: 15956686.
- [pubmed] Tanaka M, et al. "Neurons expressing relaxin 3/INSL 7 in the nucleus incertus respond to stress." Eur J Neurosci, 2005;21(6):1659-70. PMID: 15845093.
- [pubmed] McGowan BM, et al. "Central relaxin-3 administration causes hyperphagia in male Wistar rats." Endocrinology, 2005;146(8):3295-300. PMID: 15845619.
- [pubmed] Hida T, et al. "Chronic intracerebroventricular administration of relaxin-3 increases body weight in rats." J Recept Signal Transduct Res, 2006;26(3):147-58. PMID: 16777712.
- [pubmed] McGowan BM, et al. "Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis." Am J Physiol Endocrinol Metab, 2008;295(2):E278-86. PMID: 18492777.
- [pubmed] Ma S, et al. "Modulation of hippocampal theta oscillations and spatial memory by relaxin-3 neurons of the nucleus incertus." Learn Mem, 2009;16(11):730-42. PMID: 19880588.
- [pubmed] Watanabe Y, et al. "Relaxin-3-deficient mice showed slight alteration in anxiety-related behavior." Front Behav Neurosci, 2011;5:50. PMID: 21887138.
- [pubmed] Smith CM, et al. "Relaxin-3 null mutation mice display a circadian hypoactivity phenotype." Genes Brain Behav, 2012;11(1):94-104. PMID: 21899720.
- [pubmed] McGowan BM, et al. "Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing hormone." J Endocrinol, 2014;221(2):337-46. PMID: 24578294.
- [pubmed] Lenglos C, et al. "Sex-specific effects of relaxin-3 on food intake and brain expression of corticotropin-releasing factor in rats." Endocrinology, 2015;156(2):523-33. PMID: 25406021.
- [pubmed] Marwari S, et al. "Intranasal administration of a stapled relaxin-3 mimetic has anxiolytic- and antidepressant-like activity in rats." Br J Pharmacol, 2019;176(20):3899-3923. PMID: 31220339.
- [pubmed] Silvertown JD, et al. "Relaxin-3 and receptors in the human and rhesus brain and reproductive tissues." Regul Pept, 2010;159(1-3):44-53. PMID: 19778557.
- [pubmed] de Ávila C, et al. "Unveiling a novel memory center in human brain: neurochemical identification of the nucleus incertus, a key pontine locus implicated in stress and neuropathology." Biol Res, 2024;57(1):46. PMID: 39014514.
- [pubmed] Ghattas MH, et al. "Relaxin-3 is associated with metabolic syndrome and its component traits in women." Clin Biochem, 2013;46(1-2):45-8. PMID: 23018057.
- [pubmed] Zhang X, et al. "The plasma levels of relaxin-2 and relaxin-3 in patients with diabetes." Clin Biochem, 2013;46(16-17):1713-6. PMID: 23994775.
- [pubmed] Hanafy S, et al. "Serum relaxin-3 hormone relationship to male delayed puberty." Andrologia, 2018;50(2). PMID: 28786126.
- [pubmed] Erden S, et al. "Investigation of Relaxin-3 Serum Levels in terms of Social Interaction, Communication, and Appetite as a Biomarker in Children with Autism." Clin Psychopharmacol Neurosci, 2022;20(1):135-142. PMID: 35078956.
- [pubmed] Munro J, et al. "Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics." J Psychopharmacol, 2012;26(3):374-9. PMID: 21693553.
- [pubmed] Wong WLE, et al. "Investigating the role of the relaxin-3/RXFP3 system in neuropsychiatric disorders and metabolic phenotypes: A candidate gene approach." PLoS One, 2023;18(11):e0294045. PMID: 37967073.
- [pubmed] Heidari S, et al. "Expression and localisation of RXFP3 in human spermatozoa and impact of INSL7 on sperm functions." Andrologia, 2018;50(3). PMID: 29159832.
- [review] Smith CM, et al. "Relaxin-3 systems in the brain--the first 10 years." J Chem Neuroanat, 2011;42(4):262-75. PMID: 21693186.
- [review] Wong WLE, et al. "The putative role of the relaxin-3/RXFP3 system in clinical depression and anxiety: A systematic literature review." Neurosci Biobehav Rev, 2021;131:429-450. PMID: 34537263.
- [pubmed] Ryan PJ, et al. "Relaxin-3/RXFP3 system regulates alcohol-seeking." Proc Natl Acad Sci U S A, 2013;110(51):20789-94. PMID: 24297931.
Sources & Citations
Every study on this page was read from its PubMed record on November 3, 2026. Status comes from Drugs@FDA (openFDA) and ClinicalTrials.gov, 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.