RLN3 Human
Description
Central Nervous System
RLN3 is predominantly expressed in the nucleus incertus (NI) of the hindbrain, with projections to the limbic system, hypothalamus, and septohippocampal pathway . Key targets include:
-
Parahippocampal cortex (medial/lateral entorhinal cortex)
-
Perirhinal cortex (layers III–IV)
-
Lateral entorhinal cortex (patchy distribution in layers II–VI)
Peripheral Tissues
RLN3 is detected in:
-
Spinal ligaments (linked to adolescent idiopathic scoliosis (AIS))
-
Cardiovascular tissues (limited expression compared to RLN2)
Receptor Interactions
RLN3 binds to three receptors with varying affinities (Table 2):
The B-chain residues (e.g., Arg33) are critical for RXFP3 activation, while the A-chain contributes to receptor stabilization .
Central Functions
-
Stress Response: Modulates hypothalamic-pituitary-adrenal axis activity .
-
Arousal/Cognition: Regulates hippocampal theta rhythms and memory formation .
-
Feeding Behavior: Acts on hypothalamic circuits to influence appetite .
Peripheral Effects
-
Anti-Fibrotic Action: Inhibits collagen synthesis and promotes matrix metalloproteinase (MMP) activity in spinal ligaments .
-
Ligament Laxity: Elevated RLN3 correlates with generalized joint hypermobility and AIS pathogenesis .
Adolescent Idiopathic Scoliosis (AIS)
A 2022 study demonstrated that RLN3-RXFP3 signaling exacerbates spinal ligament laxity in AIS patients:
-
Plasma RLN3: 3× higher in AIS patients vs. controls (84.94 ± 64.48 ng/L vs. 29.42 ± 14.26 ng/L) .
-
Mechanism: RLN3 inhibits TGF-β/SMAD pathways and activates ERK1/2, reducing collagen I/III synthesis while increasing MMP2/9 expression .
-
Knockout Models: RLN3−/− mice show 70% reduced scoliosis incidence (19% vs. 64% in wild-type) .
Neuropsychiatric Applications
-
Anxiety/Depression: RXFP3 antagonists (e.g., R3-B1-22R) and agonists (e.g., R3-B10-27) show therapeutic potential .
-
Drug Addiction: RLN3 modulates dopamine release in the nucleus accumbens, influencing reward pathways .
Comparative Analysis with Other Relaxins
| Feature | RLN3 | RLN2 | INSL3 |
|---|---|---|---|
| Primary Receptor | RXFP3 | RXFP1 | RXFP2 |
| Key Functions | Stress, cognition, ligament laxity | Pregnancy, cardiovascular adaptation | Testicular descent, germ cell survival |
| Therapeutic Target | Anxiety, scoliosis | Heart disease, fibrosis | Infertility, birth control |
Research Tools and Applications
Product Specs
Relaxin-3 (RLN3), a member of the relaxin hormone family, exhibits both endocrine and autocrine/paracrine functions. Primarily recognized for its role in the reproductive system, relaxin, produced by the ovary, facilitates cervical ripening, pubic symphysis elongation, and uterine contraction inhibition in mammals. Deviating from Relaxins 1 and 2 in humans, RLN3 appears to have limited reproductive involvement but plays a crucial role in stress response within the brain stem. It specifically binds to the G-protein-coupled receptor GPCR135 (RXFP3) as its only known ligand. Although RLN3 exhibits binding affinity to the LGR7 (RXFP1) receptor, it is weaker compared to Relaxin-2. While RLN3 binding to LGR7 triggers intracellular cAMP increase, its interaction with GPCR135 suppresses cAMP accumulation, suggesting coupling to Gi, Go, or Gz by the receptor.
Relaxin 3, Prorelaxin H3, RXN3, Insl7, ZINS4, H3, Relaxin 3 (H3), Relaxin-3, RLN3.
B chain: RAAPYGVRLCG REFIRAVIFT CGGSRW.
Product Science Overview
Relaxin-3, also known as H3 relaxin or INSL7, is a member of the relaxin family of peptides, which are part of the insulin superfamily . Unlike human relaxins 1 and 2, which are primarily involved in reproductive processes, Relaxin-3 functions as a neuropeptide and plays a significant role in the central nervous system .
Relaxin-3 was discovered through homology searching of the human genome approximately 20 years ago . It is a disulfide-linked heterodimer composed of two chains: the A chain (Asp119-Cys142) and the B chain (Ala27-Arg53) . The predicted molecular masses of the A and B chains are 2.46 kDa and 3.04 kDa, respectively .
Relaxin-3 is primarily expressed in the brainstem and has been shown to modulate neuronal activity in multiple brain circuits . It interacts with its cognate G-protein-coupled receptor, relaxin-family peptide receptor 3 (RXFP3), to influence various neuroendocrine functions . This peptide is involved in stress response, feeding behavior, and arousal .
Recombinant human Relaxin-3 is produced using Escherichia coli (E. coli) expression systems . The protein is typically purified to a high degree of purity (>95%) and is free from endotoxins (<0.10 EU per 1 μg of protein) . The recombinant protein is often lyophilized and can be reconstituted in sterile phosphate-buffered saline (PBS) for use in various research applications .
