Relaxin receptors--new drug targets for multiple disease states.
Relaxin was discovered more than 75 years prior to the identification of the receptors that mediate its actions. There has been a slow emergence in understanding the role of relaxin, with it being denoted initially as a hormone of pregnancy due to its observed effects to relax pubic ligaments and soften the cervix of guinea pigs to facilitate parturition. However, many other physiological roles have been identified for relaxin, including cardiovascular and neuropeptide functions and an ability to induce the matrix metalloproteinases, so it is clear that relaxin is not exclusively a hormone of pregnancy but has a much wider role in vivo. The recent de-orphanisation of four receptors LGR7, LGR8, GPCR135 (SALPR) and GPCR142 (GPR100) that respond to and bind at least one of the three forms of relaxin identified to date, allows dissection of this system to determine the precise role of each receptor and enable the identification of new targets for treatment of numerous disease states. Relaxin has the potential to be useful for the treatment of scleroderma, fibrosis, in orthodontics and to facilitate embryo implantation in humans. Relaxin antagonists may act as contraceptives or prevent the development of breast cancer metastases. Recent research has added considerable knowledge to the signalling pathways activated by relaxin, which will aid our understanding of how relaxin produces its effects. The focus of this review is to bring together recent developments in the relaxin receptor field and to highlight their potential as drug targets.
Van Der Westhuizen
E T
ET
Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
Summers
R J
RJ
Halls
M L
ML
Bathgate
R A D
RA
Sexton
P M
PM
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003270:Contraceptive Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D006727:Hormone Antagonists / Q000008:administration & dosage; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045745:Scleroderma, Limited / Q000188:drug therapy / Q000378:metabolism
D003270:Contraceptive Agents; D006727:Hormone Antagonists; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors