Physiology and Molecular Biology of the Relaxin Peptide Family

Relaxin was first identified in 1926 as a substance influencing the reproductive tract and was subsequently found to be a peptide hormone with a two-chain structure similar to insulin. It is now accepted that relaxin is a member of a family of peptide hormones that includes seven members in humans—three relaxin peptides (H1, H2, and H3) and insulin-like peptides (INSL) 3, 4, 5, and 6. All these genes evolved from an ancestral relaxin-3 gene in (lower) vertebrates. The reproductive hormone relaxin is the product of one gene in most species, RLN1. Among these genes, the physiological roles of relaxin and INSL3 have been more extensively studied. Relaxin-3 is likely an important neuropeptide but has no known roles in reproduction. In contrast, relaxin has vital physiological roles during pregnancy, although its actions vary between species. Hence, relaxin has essential actions on the cervix, pubic symphysis, vagina, uterus, and mammary apparatus during pregnancy. It is also a mediator of the important cardiovascular changes that occur during pregnancy in many species. Relaxin may also play a crucial role in implantation, especially in primates. In addition, relaxin has nonreproductive actions in wound healing, cardiac protection, and as an antifibrotic agent. INSL3 is essential for testis descent by promoting gubernacular development in the fetus. It also plays an important role in female and male germ cell maturation and survival, respectively. With the recent identification of relaxin family peptide receptors, future investigations should unravel the diverse actions of relaxin and relaxin family peptides and lead to novel therapeutic applications.