Relaxins

The relaxin family of peptides comprises relaxin-1/2, relaxin-3, and insulin-like peptides (INSL) 3–6. Three of these peptides and their native receptors are present in the brain. Relaxin-1 is expressed by neurons within the anterior olfactory nucleus, piriform/neocortex, hypothalamus, and hippocampus of rat brain, wherea srelaxin-3 is highly expressed by discrete populations of neuronsin the brainstem of rodents, nonhuman primate, and other species; relaxin-3-positive axons and fibers/terminals are widely distributed throughout the forebrain. By contrast, INSL3 is detected in relatively low levels and only in neurons in some midbrain/brainstem areas. Two types of G protein-coupled receptors—RXFP1 and RXFP2, and RXFP3 and RXFP4 — preferentially interact with individual relaxin-family peptides and, apart from RXFP4, are broadly but differentially expressed in the forebrain. Experimental studies implicate relaxin-3/RXFP3 signaling in physiological roles including arousal, stress, and cognition. By contrast, functions of relaxin/RXFP1 and INSL3/RXFP2 signaling within the brain are yet to be clearly identified.