The Relaxin-Like Factor: from gene to physiology

The Relaxin-like Factor (RLF) is a relatively new member of the insulin-IGF-relaxin family, which now includes altogether eight members in mammals (Table 1; see also article by Jaspers, this volume), though a comparison with the diverse members of this family found in the completed C. elegans genome [1], suggests that more members may still be found. RLF (also known as Ley-IL) is the product of the INSL3 gene (see Table 1) and was found independently from differential cloning projects in the testes of pigs [2] and mice [3]. Subsequently, cross-hybridization or homologous PCR analysis identified equivalent genomic or cDNA sequences from a wide range of other mammalian species (human [4,5]; cows [6]; sheep [7]; marmoset monkey [8]; rats [9], as well as other species: see article by Klonisch et al., this volume). Like the closely related peptide hormone relaxin, RLF is encoded by a small gene comprising mostly only two exons (see below), with a splice junction occurring at the beginning of the region corresponding to the C-domain. Also like relaxin, RLF appears to have a three domain protein structure, with a B-domain immediately following a typical signal peptide. This is followed by the C- and A-domains respectively. Preliminary protein modelling suggests that sulfhydryl bonds link the six cysteine residues in the same configuration as for relaxin and the other members of this family.