Relaxin-family peptide and receptor systems in brain: insights from recent anatomical and functional studies

Relaxin was for many years considered primarily a hormone active within the reproductive tract with overwhelming evidence for its important roles in mammalian parturition. More recent research, however, has clearly indicated additional physiological and/or therapeutic roles for relaxin in the cardiovascular, renal and respiratory systems (see other Chapters); while a few studies have also described possible physiological effects of relaxin in the central nervous system, perhaps unsurprisingly associated with the regulation of osmotic homeostasis, blood pressure and neurohormone secretion during pregnancy and parturition. Research on relaxin and subsequently discovered, related peptides has also been particularly productive in the last five years, with some milestone discoveries (see elsewhere in this volume), including the long-awaited identification of the native receptors for relaxin and a related peptide, INSL3--the leucine-rich repeat-containing G-protein-coupled receptors-7 and -8 (LGR7/8); and the identification of a new relaxin family peptide, known as relaxin 3 and its type I G-protein-coupled receptor--GPCR135. Relaxin 3 was subsequently found to be highly conserved throughout evolution and to be the likely ancestral gene/peptide that gave rise to the current relaxin family of genes and peptides in mammals including higher primates. Interestingly, relaxin 3 and its receptor are found in highest abundance in brain, suggesting important central functions for relaxin 3/GPCR135 signaling. In this Chapter we will primarily review what is currently known about the central distribution of relaxin family peptides and their receptors and what has been described so far regarding their effects in the brain. Lastly, we will discuss likely future directions in this interesting, expanding field of research.