Relaxin

In the female, relaxin is produced by the corpus luteum of the ovary, the breast and, during pregnancy, also by the placenta, chorion, and decidua. In the male, it is produced in the prostate and is present in human semen.^[6]

Structure

Structurally, relaxin is a

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.[15]

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.^[16]

Cardiovascular function

In the

Via upregulation of VEGF, relaxin also plays a key role in blood vessel formation (angiogenesis) during pregnancy, tumour development or ischaemic wounds.^[20]

Function in other animals

Reproduction

In animals, relaxin widens the

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 oestrous cycle.^[22] Prior to ovulation, relaxin will be produced by ovarian stromal cells, which will promote secretion of gelatinases 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.^[22] Furthermore, granular and theca cells in the follicles will express relaxin in increasing levels depending on their size.^[22] During early pregnancy, the preimplantation conceptus will express relaxin, which will promote angiogenesis in the endometrium by up-regulating VEGF.^[22][23] 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.^[22]

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.^[22] Placental trophoblast cells 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.^[24] From 80 day of gestation onwards, relaxin levels will increase in the mare's serum with levels peaking in late gestation.^[24][25] Moreover, the pattern of relaxin expression will follow the expression of oestrogen, however, there is not yet a known link between these two hormones.^[25] During labour, there is a spike in relaxin 3–4 hours before delivery, which is involved in myometrial relaxation and softening of the pelvic ligaments to aid preparation of the birth canal for the delivery of the horse foetus.^[22][24] 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.^[24] In addition, if the mare undergoes an abortion then the relaxin levels will decline as the placenta ceases to function.^[24]

Cardiovascular function

Relaxin has been shown to relax

Women who have been on relaxin treatment during unrelated clinical trials have experienced heavier bleeding during their menstrual cycle, suggesting that relaxin levels could play a role in abnormal uterine bleeding.^[28] However, more research is needed to confirm relaxin as a direct cause.^{[citation needed]}

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.^[28]

Specific disorders related to relaxin have not been heavily described, yet a link to scleroderma and fibromyalgia has also been suggested.^[29]

Pregnancy

It is possible that relaxin in the placenta could be a contributing factor to inducing labour in humans and therefore serum relaxin levels during pregnancy have been linked to premature birth.^[28]

Pharmacological targets

A recombinant form of human relaxin-2 has been developed as investigational drug RLX030 (serelaxin).^{[citation needed]}

It is suggested that relaxin could be used as a therapeutic target when it comes to gynaecological disorders.^[28]

Evolution

Relaxin 1 and relaxin 2 arose from the duplication of a proto-RLN gene between 44.2 and 29.6 million years ago in the last common ancestor of

• Relaxin family peptide hormones
• Insulin/IGF/Relaxin family
• Relaxin/insulin-like family peptide receptor 1

References