Relaxin
An insulin-family peptide hormone that acts through the RXFP1 receptor to drive vasodilation, boost renal perfusion, and suppress fibrotic tissue remodeling.
Relaxin (relaxin-2; serelaxin; RLX030) is a 53-residue, two-chain polypeptide hormone structurally related to insulin, produced primarily by the corpus luteum during pregnancy and by the heart during cardiac stress. Signaling through the RXFP1 receptor, it promotes vasodilation, reduces systemic vascular resistance, increases renal perfusion, and attenuates fibrotic signaling. Its recombinant form, serelaxin, was investigated as a treatment for acute decompensated heart failure but did not achieve regulatory approval; endogenous relaxin and the RXFP1 pathway remain active areas of research in fibrosis biology and obstetric physiology.
Class
Two-chain insulin-superfamily peptide hormone (53 residues)
Routes
Intravenous, Subcutaneous
Category
Hormone & Reproductive
Researched benefits
What it's studied for
Systemic vasodilation
RXFP1 activation stimulates cAMP/PKA and nitric oxide signaling to acutely reduce systemic vascular resistance and increase cardiac output without directly raising heart rate. This hemodynamic profile distinguished relaxin from existing vasodilators and diuretics in heart failure research.
Anti-fibrotic remodeling
Relaxin upregulates matrix metalloproteinases (MMPs) that degrade excess collagen and suppresses TGF-beta-mediated fibrotic signaling. In mouse models of heart disease, serelaxin showed greater anti-fibrotic potential than the ACE inhibitor perindopril while retaining efficacy when combined with it.
Increased renal perfusion
By lowering renal vascular resistance, relaxin increases renal plasma flow and perfusion, an organ-protective effect relevant to both heart failure and pulmonary hypertension research.
Connective tissue and pelvic remodeling
As a pregnancy hormone, relaxin produces ligamentous laxity that allows the musculoskeletal and pelvic structures to stretch and accommodate fetal growth, contributing to cervical softening and pelvic ligament compliance.
Cardiac organ protection
In the RELAX-AHF trial, serelaxin improved dyspnea and reduced 180-day all-cause mortality in acute heart failure, reflecting combined hemodynamic and organ-protective activity, though a confirmatory trial did not replicate the mortality benefit.
Mechanism
How it works
Relaxin binds the RXFP1 receptor (relaxin family peptide receptor 1), a G-protein-coupled receptor. Activation stimulates adenylyl cyclase and the cAMP/PKA pathway, alongside nitric oxide signaling, producing acute vasodilation. The net hemodynamic effect is a reduction in systemic and renal vascular resistance and an increase in cardiac output that occurs without a direct effect on heart rate.
Beyond its vascular actions, relaxin exerts anti-fibrotic effects. It upregulates matrix metalloproteinases (MMPs) that degrade excess collagen and inhibits TGF-beta-driven fibrotic signaling, blunting pathological tissue remodeling. This dual profile of vasodilation plus anti-fibrotic organ protection is what mechanistically distinguished relaxin from conventional vasodilators and diuretics in cardiovascular research.
In reproductive physiology, relaxin is produced by the corpus luteum during pregnancy and promotes cervical softening and pelvic ligament compliance, generating the ligamentous laxity that allows the body to accommodate fetal growth and delivery. This same relaxation can contribute to structural changes such as lumbar lordosis and pelvic or joint pain that may persist after delivery.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Clinical (RELAX-AHF trial)
- Dose
- 30 μg/kg/day
- Frequency
- Continuous intravenous infusion
- Timing
- Initiated during acute heart failure admission
- Duration
- Up to 48 hours
- Route
- Intravenous
This is the investigational regimen used in the RELAX-AHF Phase 3 trial of recombinant human relaxin-2 (serelaxin) and does not represent an approved or self-administered protocol.
- There is no approved or standardized outpatient dosing protocol for relaxin. The only well-characterized human regimen is the intravenous serelaxin infusion used in controlled clinical trials.
- No injectable formulation is currently available outside of clinical trials, and no verified commercial providers list the peptide.
- Long-acting engineered analogs (e.g., an Fc-fusion relaxin, TX45/TX000045) are being developed with extended half-lives of 2 to 3 weeks but remain in early investigational stages.
Evidence
Research & clinical studies (8)
Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial
In 1,161 patients, serelaxin (30 μg/kg/day IV) significantly improved the dyspnoea VAS AUC endpoint (p=0.007) and reduced 180-day all-cause mortality (HR 0.63, p=0.019) in acute heart failure.
PMID 23141816Serelaxin has greater anti-fibrotic potential than perindopril but maintains its anti-fibrotic efficacy in the presence of perindopril in normotensive mouse models of heart disease
Serelaxin produced greater anti-fibrotic effects than the ACE inhibitor perindopril and retained its efficacy when combined with it, supporting its potential as an adjunct to standard therapy.
PMID 42176886Development of a long-acting relaxin for the treatment of pulmonary hypertension
TX45, an Fc-fusion of human relaxin-2, showed an extended half-life of 2 to 3 weeks and reduced pulmonary hypertension markers, including increased renal plasma flow and reduced cardiac hypertrophy, in animal models.
PMID 42173817[Advances in targeted pharmacotherapies for pulmonary hypertension associated with left heart disease]
Long-acting relaxin analogs and activin signaling inhibitors showed potential benefit in preliminary studies for pulmonary hypertension associated with left heart disease, where existing PAH therapies lack proven efficacy.
PMID 42135043Incidence of sacral somatic dysfunction in vaginal delivery after spontaneous labor
Pregnancy-elevated relaxin caused ligamentous laxity accommodating fetal growth but contributed to structural changes such as lumbar lordosis, pelvic pain, and joint pain that may persist postpartum.
PMID 42153514Divergent activation of the RXFP1 relaxin receptor by protein and small molecule agonists
Protein and small-molecule agonists activate the RXFP1 relaxin receptor through divergent mechanisms, informing receptor pharmacology and drug design.
PMID 42327029Association of Relaxin-1 Levels with Mortality in Sepsis and Septic Shock
Circulating relaxin-1 levels were associated with mortality outcomes in patients with sepsis and septic shock.
PMID 42355830Huoxue Jiegu compound capsule accelerates tibial fracture healing via angiogenesis-driven repair mechanisms
A compound accelerated tibial fracture healing through angiogenesis-related signaling, with the Relaxin pathway among the implicated molecular mechanisms enhancing blood vessel formation.
PMID 42200075Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Cardiovascular conditions
- Kidney or liver conditions
- Pregnancy or nursing
Relaxin carries a moderate risk profile in research contexts. Its potent vasodilatory action warrants caution in individuals with cardiovascular, renal, or hepatic conditions. It remains investigational, and reported considerations should be reviewed carefully with a qualified healthcare professional before any use.
FAQ
Relaxin — common questions
What is Relaxin?
Relaxin (relaxin-2; serelaxin; RLX030) is a 53-residue, two-chain polypeptide hormone structurally related to insulin. It is produced by the corpus luteum during pregnancy and by the heart during cardiac stress, and it acts through RXFP1 receptors to promote vasodilation, reduce systemic vascular resistance, increase renal perfusion, and attenuate fibrotic signaling.
What is Relaxin primarily studied for?
Research focuses on connective tissue remodeling, anti-fibrotic effects, pelvic floor support, fertility support, and cardiac protection, most prominently as an investigational treatment for acute decompensated heart failure.
What does the research show about Relaxin?
The RELAX-AHF Phase 3 trial of 1,161 patients showed that serelaxin (30 μg/kg/day IV) significantly improved dyspnea and reduced 180-day all-cause mortality in acute heart failure. However, the confirmatory RELAX-AHF-2 trial failed to meet its co-primary endpoint of cardiovascular death reduction, and the program was discontinued.
Is Relaxin FDA approved?
No. Serelaxin has no FDA approval and no approved indication in any jurisdiction. Regulatory applications in the US and Europe were not approved, and no injectable formulation is available outside of clinical trials.
How is Relaxin administered?
In clinical trials, recombinant relaxin-2 (serelaxin) was given as a continuous intravenous infusion. There is no established subcutaneous or outpatient self-administration protocol.
What are the side effects of Relaxin?
Reported contraindications and considerations include cardiovascular conditions, kidney or liver conditions, and pregnancy or nursing. Its vasodilatory action can lower blood pressure. This is educational information only; consult a qualified healthcare professional before use.
Are there newer relaxin therapeutics in development?
Yes. Long-acting engineered analogs such as TX45 (an Fc-fusion of human relaxin-2) with half-lives of 2 to 3 weeks are being investigated for pulmonary hypertension, but they remain in early clinical stages.
