Relaxin/insulin-like family peptide receptor 2

Relaxin/Insulin-like Family Peptide Receptor 2

The Relaxin/Insulin-like Family Peptide Receptor 2 (RXFP2) is a G-protein coupled receptor that plays a crucial role in various physiological processes. It is a member of the relaxin/insulin-like family peptide receptor subfamily and is primarily expressed in reproductive tissues.

Structure

The RXFP2 gene is located on chromosome X in humans and is composed of 11 exons. The receptor protein consists of a large extracellular domain, seven transmembrane helices, and an intracellular C-terminal tail. The extracellular domain contains leucine-rich repeats, which are involved in ligand binding.

Function

RXFP2 is primarily activated by two ligands: relaxin and insulin-like peptide 3 (INSL3). Relaxin is a peptide hormone that is mainly produced by the corpus luteum during pregnancy, while INSL3 is predominantly secreted by Leydig cells in the testes.

Upon ligand binding, RXFP2 activates intracellular signaling pathways, including the cyclic adenosine monophosphate (cAMP) pathway. This leads to the activation of downstream effectors, such as protein kinase A (PKA) and extracellular signal-regulated kinases (ERKs). These signaling cascades regulate various cellular processes, including cell proliferation, differentiation, and survival.

Role in Reproduction

RXFP2 is primarily known for its role in reproductive processes. In females, relaxin binding to RXFP2 promotes the growth and remodeling of the reproductive tract during pregnancy. It helps to soften the cervix and relax the pelvic ligaments, facilitating childbirth. Additionally, relaxin has been shown to have anti-fibrotic and anti-inflammatory effects in various tissues.

In males, INSL3 binding to RXFP2 is essential for the development and function of the testes. It plays a crucial role in the descent of the testes during fetal development, as well as the regulation of testosterone production by Leydig cells. Mutations in the RXFP2 gene can lead to cryptorchidism, a condition characterized by undescended testes.

Clinical Implications

The involvement of RXFP2 in reproductive processes makes it an attractive target for therapeutic interventions. Modulating RXFP2 signaling could potentially be used to treat conditions such as preterm labor, fibrosis, and certain types of cancer.

Furthermore, mutations in the RXFP2 gene have been associated with various reproductive disorders. For example, loss-of-function mutations can cause male infertility due to impaired testicular descent or reduced testosterone production. Understanding the molecular mechanisms underlying RXFP2 function may lead to the development of novel diagnostic tools and targeted therapies for these conditions.

References

1. Bathgate RA, et al. (2013). Relaxin family peptides and their receptors. Physiol Rev, 93(1), 405-480. 2. Hsu SY, et al. (2002). The three subfamilies of leucine-rich repeat-containing G protein-coupled receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for LGR7. Mol Endocrinol, 16(7), 1350-1364. 3. Ivell R, et al. (2013). Relaxin and the insulin-like factor 3 (INSL3) system in human testicular development and function. Ann Endocrinol (Paris), 74(2), 79-89.

See Also

• Relaxin
• Insulin-like Peptide 3
• G-Protein Coupled Receptors
• Reproductive System
• Cryptorchidism