IngentaConnect The relaxin peptide family and their novel G-protein coupled rece...

Authors: Daniel J. Scott¹; Tracey Wilkinson¹; Geoffrey W. Tregear¹; Ross A. D. Bathgate²

Source: Letters in Peptide Science, Volume 10, Number 5, 2003 , pp. 393-400(8)

Publisher: Springer

Abstract:

Relaxin-1 is a heterodimeric peptide hormone primarily produced by the pregnant corpus luteum and/or placenta and is involved in many essential physiological processes centered on its action as a potent extracellular matrix (ECM) remodeling agent. Insulin-like peptide 3 (INSL3), also known as relaxin-like factor, is predominantly expressed in the Leydig cells of the testes and is an important mediator of testicular descent. The relaxin-1 equivalent peptide in humans is actually the product of the human RLN2 gene, human 2 (H2) relaxin. Recently identified and thought to be the ancestral relaxin, relaxin-3 is specifically expressed in the nucleus incertus of the mouse and rat brain and is most likely an important neuropeptide. Each of the hormones above act on cell membrane G-protein coupled receptors (GPCRs). The relaxin-1 receptor is leucine-rich repeat-containing GPCR 7 (LGR7) whereas INSL3 acts on the closely related LGR8. These receptors have large extra-cellular domains containing multiple leucine-rich repeats (LRRs) and a unique LDL receptor-like cysteine-rich motif (LDLR-domain). Relaxin-3 will bind and activate LGR7 with 50-fold lower activity than H2 relaxin. Two relaxin-3 selective GPCRs; somatostatin and angiotensin like peptide receptor (SALPR) and GPCR 142 were recently identified, these type I GPCRs are unrelated to LGR7 and LGR8. The discovery and characterisation of these receptors is greatly aiding the quest to unravel the mechanics of these important hormones, however with three other family members, insulin-like peptides 4–6 (INSL4, INSL5 and INSL6) with unknown functions and unidentified receptors, there is still much to be learnt about this hormone family.

Keywords: G-protein coupled receptors; insulin-like peptides; INSL3; LGR7; LGR8; relaxin

Document Type: Research article

DOI: 10.1007/s10989-004-2389-4

Affiliations: 1: Howard Florey Institute, University of Melbourne, Victoria 3010, Australia 2: Howard Florey Institute, University of Melbourne, Victoria 3010, Australia (), Email: r.bathgate@hfi.unimelb.edu.au

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The relaxin peptide family and their novel G-protein coupled receptors