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Relaxin is a protein hormone of about 6000 Da, first described in 1926 by Frederick Hisaw.
The relaxin family peptide hormones belong to the insulin superfamily and consists of seven peptides of high structural but low sequence similarity; relaxin-1 (RLN1), 2 (RLN2) and 3 (RLN3), and the insulin-like (INSL) peptides, INSL3, INSL4, INSL5 and INSL6. The functions of relaxin-3, INSL4, INSL5, and INSL6 remain uncharacterised.
Relaxin is produced from its prohormone, "prorelaxin", by post-translational proteolytic cleavage of its signal peptide and C domain peptide. (2019). 9780128012383, Elsevier. ISBN 9780128012383
Relaxin is believed to relax the uterine muscle and to loosen the ligaments holding the pelvic bones together, in order to prepare the birth canal for the birth. It may cause a woman to feel that other ligaments are looser, such as in the shoulders, knees, hips, and ankles.
In males, relaxin enhances motility of sperm in semen. Also, relaxin is found in higher than normal concentrations in the ejaculate of men who were born without their vas deferens and seminal vesicles.
Via upregulation of VEGF, relaxin also plays a key role in blood vessel formation (angiogenesis) during pregnancy, tumour development or ischaemic wounds.
In horses ( Equus caballus), relaxin is also an important hormone involved in pregnancy; however, before pregnancy occurs, relaxin is expressed by ovarian structures during the Estrous cycle. Prior to ovulation, relaxin will be produced by ovarian stromal cells, which will promote secretion of and tissue inhibitors of metalloproteinases. These enzymes will then aid the process of ovulation, which will lead to the release of a developed follicle into the fallopian tube. Furthermore, granular and theca cells in the follicles will express relaxin in increasing levels depending on their size. During early pregnancy, the preimplantation conceptus will express relaxin, which will promote angiogenesis in the endometrium by up-regulating VEGF. This will allow the endometrium to prepare for implantation. In horses alone, the embryo in the uterus will express relaxin mRNA at least 8 days after ovulation. Then as the conceptus develops expression will increase, which is likely to promote embryo development.
In addition to relaxin production by the horse embryo, the maternal placenta is the main source of relaxin production, whereas in most animals the main source of relaxin is the corpus luteum. Placental Trophoblast produce relaxin, however, the size of the placenta does not determine the level of relaxin production. This is seen because different breeds of horses show different relaxin levels. From 80 day of gestation onwards, relaxin levels will increase in the mare's serum with levels peaking in late gestation. Moreover, the pattern of relaxin expression will follow the expression of Estrogen, however, there is not yet a known link between these two hormones. During labour, there is a spike in relaxin 3–4 hours before delivery, which is involved in Myometrium relaxation and softening of the pelvic ligaments to aid preparation of the birth canal for the delivery of the horse foetus. Following birth, the levels of relaxin will gradually decrease if the placenta is also delivered, however, if the placenta is retained in the mare then the levels will remain high. In addition, if the mare undergoes an abortion then the relaxin levels will decline as the placenta ceases to function.
Several animal studies have found relaxin to have a cardioprotective function against ischaemia and reperfusion injury, by reducing cellular damage, via anti-Apoptosis and anti-inflammatory effects. Relaxin has been shown to reduce cardiac fibrosis in animal models by inhibiting cardiac fibroblasts secreting collagen and stimulating matrix metalloproteinase.
In the European rabbit ( Oryctolagus cuniculus), relaxin is associated with squamous differentiation and is expressed in tracheobronchial epithelial cells as opposed to being involved with reproduction.
Relaxin receptors have been found in the heart, smooth muscle, the connective tissue, and central and autonomous nervous system.
A lower expression of relaxin has been found amongst women who have endometriosis. The research in this area is limited and more studying of relaxin's contribution could contribute greatly to the understanding of endometriosis.
Specific disorders related to relaxin have not been heavily described, yet a link to scleroderma and fibromyalgia has also been suggested.
It is suggested that relaxin could be used as a therapeutic target when it comes to gynaecological disorders.
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