<p> The insulin family of proteins groups together several evolutionarily related active peptides [<cite idref="PUB00003973"/>]: these include insulin [<cite idref="PUB00003972"/>, <cite idref="PUB00003970"/>], relaxin [<cite idref="PUB00053639"/>, <cite idref="PUB00053640"/>], insect prothoracicotropic hormone (bombyxin) [<cite idref="PUB00053641"/>], insulin-like growth factors (IGF1 and IGF2) [<cite idref="PUB00023078"/>, <cite idref="PUB00053642"/>], mammalian Leydig cell-specific insulin-like peptide (gene INSL3), early placenta insulin-like peptide (ELIP) (gene INSL4), locust insulin-related peptide (LIRP), molluscan insulin-related peptides (MIP), and Caenorhabditis elegans insulin-like peptides. The 3D structures of a number of family members have been determined [<cite idref="PUB00023078"/>, <cite idref="PUB00053642"/>, <cite idref="PUB00037375"/>]. The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of 4 cysteines in their A chain, the first of which is linked by a disulphide bond to the third, while the second and fourth are linked by interchain disulphide bonds to cysteines in the B chain. </p> <p> Insulin is found in many animals, and is involved in the regulation of normal glucose homeostasis. It also has other specific physiological effects, such as increasing the permeability of cells to monosaccharides, amino acids and fatty acids, and accelerating glycolysis and glycogen synthesis in the liver [<cite idref="PUB00003972"/>]. Insulin exerts its effects by interaction with a cell-surface receptor, which may also result in the promotion of cell growth [<cite idref="PUB00003972"/>]. </p> <p> Insulin is synthesised as a prepropeptide from which an endoplasmic reticulum-targeting sequence is cleaved to yield proinsulin. The sequence of prosinsulin contains 2 well-conserved regions (designated A and B), separated by an intervening connecting region (C), which is variable between species [<cite idref="PUB00003970"/>]. The connecting region is cleaved, liberating the active protein, which contains the A and B chains, held together by 2 disulphide bonds [<cite idref="PUB00003970"/>]. </p><p>Relaxin has diverse actions in the reproductive tract and in other tissuesduring pregnancy [<cite idref="PUB00010561"/>]. Although binding sites for relaxin have been found inreproductive tissue, the nature of the receptor was previously unknown.Recently, two orphan GPCRs, LGR7 and LGR8, have been identified as receptorsfor the hormone. These two receptors contain large extracellular N-terminiwith leucine-rich repeat regions, and are structurally similar to thegonadotropin and thyrotropin receptors. LGR7 is expressed in the brain,kidney, testis, placenta, uterus, ovary, adrenal gland, prostate, skin andheart, while LGR8 is expressed mainly in the brain, kidney, muscle, testis,thyroid, uterus, peripheral blood cells and bone marrow. Upon binding toLGR7 or 8, relaxin stimulates a dose-dependent increase in cyclic AMPproduction, indicating coupling of the receptors to G proteins.</p> Relaxin receptor