Relaxin

Relaxin is a hormone that is secreted by the human body primarily during pregnancy. Relaxin can be considered a pleiotropic hormone. It means that the research has found various evidence that suggests that the relaxin hormone works in various different pathways one of which is pregnancy. It is important to note that relaxin is a peptide hormone that is a protein. Relaxin is also related to the insulin superfamily, similar to every hormone the relaxin also requires a specific receptor to perform its function. This article deals with the detail of the hormone, structure of the hormone, function, and synthesis of the hormone, the disorders related to the hormone will also be discussed.

Relaxin Synthesis

Relaxin is a major peptide hormone secreted by the human body, the bulk circulating relaxin is mostly secreted by the corpus luteum in the female. The minor organs that secrete this hormone include the placenta, chorion, and decidua. During pregnancy, the placenta is the major source of hormone synthesis.

Chorion can be defined as the outermost layer of the human fetus, thus it can be easily concluded that relaxin has some rile in pregnancy. Decidua can be defined as the mucosal lining that is modified during pregnancy. It is a modified lining of the uterus, it is also important to know that the decidua formation is stimulated by the progesterone, thus progesterone and relaxin both play role in pregnancy. Progesterone also indirectly regulates the synthesis of the relaxin as the maintenance of the corpus leuteum during pregnancy is due to the progesterone regulation.

The parenchymal cell of the mammary glands has also shown evidence of relaxin secretion during the breastfeeding period. 

In non-pregnant females, the hormone is secreted by the corpus leuteum but due to the ovarian cycle the corpus leuteum gets degraded and only a small amount of hormone is found. The hormone synthesis is synced with the sudden increase in LH concentration during the luteal phase of the ovarian cycle. In this phase, the progesterone concentration increases due to the regulation of the LH hormone. The increase in relaxin concentration is seen after 9-10 days of LH surge. Thus it can be said that progesterone and relaxin secretion are in turn regulated by the Leutinizing Hormone (LH).

Apart from its role in females, relaxin is also secreted in males. The relaxin is produced by an organ named the prostate in the male body. The prostate can be defined as the accessory  (helping) gland of the human male reproductive system. The major role of the prostate gland is to maintain the alkalinity of the sperm and improve sperm motility. Relaxin helps in improving the mobility of the male gametes that are sperms. It is interesting to know that the relaxin hormone is secreted directly into the seminal plasma.

Relaxin Structure

Relaxin belongs to the superfamily of insulin.  Like insulin, it is a peptide hormone. The molecular weight of relaxin is about  600Da. The relaxin is not synthesized in its active form, they are synthesized as precursor relaxin hormone, these are known as preprorelaxin. This preprorelaxin undergoes modification to yield the final active form of the enzyme. They mainly undergo the process of proteolytic cleavage. The relaxin similar to insulin is a heterodimer, which is made up of two different peptide chains. These chains are named as chain A and chain B. These chains are not joined together by the disulfide bond in the are proactive form. It is during the proteolytic cleavage of the chain that the accessory parts are removed. During this process, chain A and chain B of the hormone are joined by the disulfide linkage between the cysteine residues of both chains. It is an interesting observation that the location of the disulfide linkage and the amino acid associated with it is evolutionary conserved. It is also found that the tertiary structure of the protein is the same in all the species in which relaxin is synthesized.

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Function of relaxin

There are various biological effects of relaxin on the physiology of the human body, as it is well understood that relaxin is a pleiotropic hormone that is the function over different arrays of the pathway. Some of the biological effects of the relaxin hormone are listed below

1. They affect the connective tissue components of the body

2. They affect the uterine mobility of the female body. Progesterone and relaxin plays important role in uterine mobility during pregnancy.

3. Relaxin also affects the mammary gland during the breastfeeding period.

4. Relaxin also has some effects on the cardiovascular system. It is important to note that relaxin is minorly produced by the cardiac tissues

5. Relaxin also helps in maintaining the homeostasis of the body.

6. Relaxin sometimes acts as a growth factor, thereby regulating the metabolism of the body. They in turn regulate the cell cycle because they function as a growth factor they act as mitogens stimulating the cell division.

7. They also play important role in the respiratory system they help in improving the antiasthmatic effects.

8. They play a major role in improving the sperm motility 

9. Relaxin also affects the functioning of the brain and pituitary gland, as mentioned earlier, relaxin works as a feedback control regulator that inhibits the synthesis of luteinizing hormone from the anterior of the brain and stimulates the secretion of growth hormone.

10. Relaxin helps in the retention of fluid balance this case especially holds true for pregnant females. During the pregnancy, there is an increase in maternal fluids because of increased retention of sodium in the body. Relaxin receptors are expressed in the homeostasis center of the brain, relaxin is also associated with the secretion of ANP, which plays important role in maintaining the body’s fluid homeostasis.

Role of Relaxin in Pregnancy

Relaxin plays an important role in pregnancy, during pregnancy the majority of the hormone is secreted by the placenta. The other important function of the hormone is mediated by affecting the connective tissues. Relaxin’s effect on the connective tissue plays a major role in the parturition of the fetus. Relaxin lengthens the interpubic ligament, this lengthening results in the softening of the connective tissue of the cervix, which also known as the birth canal. This effect is in synergy with the steroid action. The steroidal hormone involved in this case is progesterone. Both progesterone and relaxin help in the softening of the birth canal. Research has shown evidence that this is due to collagen remodeling which is induced by relaxin. 

Relaxin also affects uterine mobility in pregnant females. Relaxin plays the classic role of myometric contraction. The plyometric contraction is achieved by increasing the intracellular concentration of the cAMP this results in the induction of a signaling cascade that increases the concentration of the calcium ion, which in turn leads to the decrease in phosphorylation of the light chain of myosin. This ultimately leads to relaxation in the contractile apparatus of the uterus. This rhythmic contraction and relaxation of the uterine wall are very important for the parturition.

Progesterone and relaxin both are very important hormones that are present during pregnancy. The role of relaxin and the concentration of relaxin is partially controlled by the concentration of progesterone. Progesterone helps in the maintenance of the corpus leuteum which releases relaxin thus indirectly regulating it.  Relaxin act as a feedback regulator for the LH hormone which stimulates the secretion of progesterone. Thus both the hormones work as regulators of each other.

Role of Relaxin in the Cardiovascular System.

Relaxin has a vasodilatory role in the cardiac system. Relaxin exerts an effect on the blood vessel by inducing the pathway that activates nitric oxide. The induction of the signaling cascade begins with the activation of NFKB genes, which leads to the expression of the receptors of nitric oxide. Nitric oxides bind to the intracellular receptor which cries the signaling pathway that results in the closure of the calcium channel and the opening of the potassium channel. The net result of this is vasodilation that is relaxation in the smooth muscles.

Receptors of Relaxin

Like all the hormones relaxin mediates its function by binding to the specific receptors, some of the receptors of the hormone are mentioned below.

1. Relaxin receptor LGR7 (RXFP1) and 

2. Receptor LGR8 (RXFP2)

They are G- protein receptors. These receptors are found in the anterior pituitary, heart, smooth muscles, connective tissue, and central nervous system of the body.