Relaxin-3

experimental

Also known as: Insulin-like peptide INSL7, Prorelaxin H3, RLN3, Q8WXF3

Relaxin-3 (RLN3), also known as insulin-like peptide 7 (INSL7), is a neuropeptide belonging to the relaxin/insulin superfamily. Its mechanism of action primarily involves binding to the G protein-coupled receptor RXFP3 (relaxin family peptide receptor 3), which is predominantly expressed in the brain, particularly in regions associated with stress, arousal, and feeding behavior. Activation of RXFP3 triggers intracellular signaling cascades, including inhibition of cAMP production and modulation of MAPK pathways, thereby influencing neuropeptide signaling processes related to stress responses, circadian rhythms, and energy homeostasis. Key research findings indicate that Relaxin-3 plays a significant role in modulating stress-related behaviors, feeding regulation, and arousal. Animal studies have shown that central administration of Relaxin-3 increases food intake and promotes stress-induced anxiety-like behaviors, while RXFP3 antagonists reduce these effects. Additionally, Relaxin-3 has been implicated in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and may influence sleep-wake cycles. However, its precise physiological roles in humans remain under investigation, with most data derived from preclinical models. Clinically, Relaxin-3 is considered an experimental target for potential therapeutic interventions in stress-related disorders, obesity, and sleep disturbances. Its selective expression in the brain and involvement in key neuroendocrine pathways make it a promising candidate for drug development, though no approved therapies currently exist. Further research is needed to translate these findings into clinical applications. For research purposes only — not medical advice.

Key data

Category
Hormonal & Endocrine
Sequence
MARYMLLLLLAVWVLTGELWPGAEARAAPYGVRLCGREFIRAVIFTCGGSRWRRSDILAHEAMGDTFPDADADEDSLAGELDEAMGSSEWLALTKSPQAFYRGRPSWQGTPGVLRGSRDVLAGLSSSCCKWGCSKSEISSLC
Molecular weight
15451 g/mol
Research status
experimental
References
294
Tags
uniprot, 3d-structure, cleavage-on-pair-of-basic-residues, direct-protein-sequencing, disulfide-bond, hormone, reference-proteome, secreted, signal

Mechanism of action

May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4

Research & studies

Molecular mechanism underlying non-discriminatory recognition of relaxin-3 by RXFP3 and RXFP4
Communications biology · 2025 · PubMed
Single nucleus/cell RNA-seq of the chicken hypothalamic-pituitary-ovarian axis offers new insights into the molecular regulatory mechanisms of ovarian development
Zoological research · 2024 · PubMed
Hypothalamic-hindbrain circuit for consumption-induced fear regulation
Nature communications · 2024 · PubMed

LH GAD2 neurons activate NI RLN3 neurons via excitatory connections during feeding with fear-conditioned stimuli.; Activation of the LH GAD2-NI RLN3 circuit reduces CS-induced freezing behavior in male mice.; NI RLN3 projections to the lateral mammillary nucleus and RLN3 signaling in the LM mediate the decrease in freezing.; The study reveals a mechanism for coordinating nutrient intake with threat avoidance.

Targeting the relaxin-3/RXFP3 system: a patent review for the last two decades
Expert opinion on therapeutic patents · 2024 · PubMed

Patent activity on the relaxin-3/RXFP3 system has increased over the last two decades.; Development of RXFP3-specific peptides and small-molecule ligands is a key research focus.; Behavioral studies in rodents suggest the system is a target for obesity, anxiety, and alcohol addiction.

Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress
Computational and mathematical methods in medicine · 2022 · PubMed
The Relaxin-3 Receptor, RXFP3, Is a Modulator of Aging-Related Disease
International journal of molecular sciences · 2022 · PubMed
Distribution, physiology and pharmacology of relaxin-3/RXFP3 systems in brain
British journal of pharmacology · 2017 · PubMed
Synthetic relaxins
Current opinion in chemical biology · 2014 · PubMed

Relaxin-2 is a pleiotropic hormone with vasodilator, cardiac stimulant, and antifibrotic roles.; Relaxin-3 is primarily a neuropeptide involved in stress and metabolic control.; Both relaxins share the unique three-disulfide heterodimeric structure of insulin.; Chemical and recombinant DNA synthesis methods have been crucial for studying relaxin biology.

Frequently asked questions

What is Relaxin-3?

Relaxin-3 (RLN3), also known as insulin-like peptide 7 (INSL7), is a neuropeptide belonging to the relaxin/insulin superfamily. Its mechanism of action primarily involves binding to the G protein-coupled receptor RXFP3 (relaxin family peptide receptor 3), which is predominantly expressed in the brain, particularly in r

How does Relaxin-3 work?

May play a role in neuropeptide signaling processes. Ligand for LGR7, RXFP3 and RXFP4

What is the research status of Relaxin-3?

Relaxin-3 is currently classified as experimental, with 294 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Relaxin-3?

Relaxin-3 has a molecular weight of approximately 15451 g/mol.

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