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Relaxin Receptor Family

Relaxin receptors are receptors that mediate their functions via binding the relaxin family peptides, including relaxin, insulin-like peptide 3 (INSL3), relaxin-3, and insulin-like peptide 5 (INSL5). Relaxin has many roles in female and male reproduction, as a neuropeptide in the central nervous system, as a vasodilator and cardiac stimulant in the cardiovascular system, and as an antifibrotic agent. Relaxin-3, in mammals, is primarily a neuropeptide involved in stress, memory, and appetite regulation. INSL3 was highly expressed in the Leydig cells of the testis and it has a critical role in testis descent, gubernaculum development, and may be involved in the maintenance of ovarian function. INSL5 is widely distributed particularly in the gastrointestinal tract. It may be involved in glucose homeostasis.

Each relaxin peptide is the cognate ligand for a specific G protein-coupled receptor (GPCR) and mediates a wide variety of physiologic functions. In humans, RXFP1 is the cognate receptor for human relaxin while RXFP2 is the cognate receptor for INSL3. These two receptors are structurally similar receptors that use some common signaling mechanisms. RXFP3 and RXFP4 are the targets for relaxin-3 and INSL5, respectively. They are closely related receptors but are involved in different physiologic functions. Due to their wide distribution and important roles in different physiologic functions, it is clear that they could be further studied and exploited for therapeutic benefit. Here, we briefly summarize the structure, signal transduction pathways, ligand development, and recent research advances of these four receptors.

Human Relaxin Receptor Members
RXFP1 RXFP2 RXFP3 RXFP4

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Relaxin Receptor Family

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