What is Relaxin?

Relaxin is a peptide hormone that has a variety of actions on reproductive and non-reproductive organs. It is mainly produced by the ovary, breast and, during pregnancy, placenta, but other tissues including the prostate and heart are also able to produce and respond to relaxin. As the name suggests, tissues soften, relax or give way upon exposure to relaxin. It softens the reproductive organs and nipples of pregnant women for smooth delivery and milk production. Relaxin also assists in the control of blood volume, kidney function and blood pressure during pregnancy. Recent research has identified the receptor for relaxin as part of a family called the leucine-rich repeat containing guanine-nucleotide binding (G-protein)-coupled receptors, or, in short, LGR7. Our understanding of relaxin, its receptor and its activity has grown rapidly in the last 10 years. Among these, its actions on non-reproductive organs, especially the link between relaxin and heart disease has attracted great attention. 

Relaxin- a marker of heart disease?

Recent research on the link between heart disease & reproductive hormone relaxin found that relaxin level is increased in heart failure. The level is also found to rise in line with the severity of heart failure: the higher the level, the worse the condition. There is a dramatic upregulation (switching on and increased responsiveness) of the relaxin gene (that controls the production of relaxin) in the failing heart, suggesting that the increased relaxin level in heart failure is coming from the heart. Experiments on diseased animals showed similar results – 4-5 times upregulation of the relaxin gene in the heart when heart failure is present. Some researches therefore proposed that relaxin is a marker of heart failure. The rise of relaxin level in heart failure has since been confirmed by some other clinical reports, but its role as a marker of heart failure remains a question.

Functional role for relaxin?

Given at doses intended for treatment, relaxin has an effect on increasing the rate and force of contraction of the heart. However, at physiological range (normal level in the body), such an action is not evident. It causes the kidney vessels to open up, and also prevents fibrosis (formation of fibrous/scar-like tissue). Male mice which had deletion of the relaxin gene develop heart failure, and the fibrosis feature can be reversed by giving them relaxin.

Therapeutic potential of relaxin?

The potential of relaxin as a therapy has been studied and strongly suggested. Of these, its ability to prevent formation of scar-like tissue in the heart is documented. It is able to change the balance between the production and breakdown of collagen, preventing hardening. Not only does it reverse fibrosis in the heart, it also reverses fibrosis in the kidneys in rats with high blood pressure. Recently, it has been shown that by delivering the relaxin gene into the body, similar effect in the heart can be achieved. In animal models, relaxin was also shown to produce protection against clots and lack of blood supply, and stop vessels from closing up. It has effect on control of water intake and kidney actions, thus regulating the balance of blood volume too.

Future research on relaxin

Further research is needed with regard to the potential of relaxin as a therapy in heart diseases. Its role in giving signals and after a heart attack as well as its implication when the level is high need to be studied. Genetically modified mice will be of much use in this setting. (Kindly contributed by Dr Xiao-Jun Du, MBBS, M.Med., PhD, Experimental Cardiology Laboratory, Baker Heart Research Institute, Melbourne, Australia.)

References

  1. Sherwood OD. Relaxin’s physiological roles and other diverse actions. Endocr Rev 2004;25:205-234
  2. Conrad KO, Novak J. Emerging role of relaxin in renal an cardiovascular function. Am J Physiol Regul Integ comp Physiol 2004;287:R256-R261
  3. Dschietzig T, Richter C, Bartsch C, Laule M, Ambruster FP, Baumann G, Stangl K The pregnancy hormone relaxin is a player in human heart failure. FASEB J 2001;15:2187-2195
  4. Du XJ, Samuel CS, Gao XM, Zhao L, Parry LJ, Tregear GW 2003 Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype. Cardiovasc Res 57:395-404
  5. Samuel CS., Unemori EN., Mookerjee I, Bathgate RAD., Layfield SL., Mak J, Tregear GW, Du XJ: Relaxin modulates cardiac fibroblast proliferation, differentiation and collagen production and reverses cardiac fibrosis in vivo. Endocrinology 2004;145(9):4125-4133
  6. Lekgabe ED, Kiriazis H, Zhao C, Xu Q, Moore XL, Su Y, Ross A.D. Bathgate RAD, Du XJ, Samuel CS. Relaxin reverses cardiac and renal fibrosis in spontaneously hypertensive rats. Hypertension 2005;46:412-418
  7. Perna AM, Masini E, Nistri S, Briganti V, Bigazzi M, Bani Sacchi T, Pieroni C, Bani D. Novel drug development opportunity for relaxin in acute myocardial infarction: evidences from a swine model. FASEB J 2005;19:1525-1527