Relaxin

1. Overview

Relaxin is a peptide hormone primarily involved in the female reproductive system, especially during pregnancy. It facilitates changes in connective tissues to accommodate fetal growth and delivery. Beyond reproduction, relaxin also has systemic effects on the cardiovascular system, collagen turnover, and renal function. Initially discovered in females, relaxin is now known to be present and functionally active in both sexes.

2. Location

Relaxin is produced in several tissues, depending on sex and physiological state:

• In females:

  • Produced by the corpus luteum during the luteal phase and early pregnancy.

  • Later during pregnancy, synthesized by the placenta and decidua.

• In males:

  • Secreted in small amounts by the testes, particularly by Leydig cells.

• Other sites:

  • Heart, blood vessels, kidneys, and brain also express relaxin and its receptors, indicating wider systemic roles.

3. Structure

Relaxin is a small peptide hormone belonging to the insulin-like hormone family. The most studied form in humans is Relaxin-2. It is composed of two peptide chains (A and B) connected by disulfide bridges, similar in structure to insulin. The hormone is encoded by the RLN2 gene on chromosome 9 and acts through the relaxin family peptide receptors (RXFPs), primarily RXFP1.

4. Function

Relaxin exerts diverse effects across reproductive and non-reproductive systems:

• In pregnancy:

  • Relaxes the uterine musculature to prevent premature contractions.

  • Softens the cervix and pubic symphysis in preparation for labor.

  • Increases cardiac output and renal blood flow to support fetal demands.

• In connective tissue:

  • Inhibits collagen synthesis and promotes matrix remodeling.

• In cardiovascular system:

  • Acts as a vasodilator, improving arterial compliance and reducing vascular resistance.

• In kidneys:

  • Enhances glomerular filtration rate and promotes sodium excretion.

5. Physiological role(s)

Relaxin plays key physiological roles across life stages and body systems:

• Reproductive function: Prepares the body for labor and delivery by remodeling connective tissues in the pelvis and cervix.

• Cardiovascular adaptation in pregnancy: Reduces systemic vascular resistance and increases blood flow to vital organs like kidneys and uterus.

• Renal function: Supports increased filtration demands in pregnancy and contributes to fluid and electrolyte balance.

• Tissue remodeling: Plays a role in wound healing and organ adaptation via collagen breakdown and tissue regeneration.

• Anti-fibrotic effects: Demonstrated in the heart, lungs, and kidneys, where relaxin inhibits fibrosis in pathological conditions.

6. Clinical Significance

Relaxin has several important clinical implications, both physiologically and therapeutically:

• Pregnancy-related changes:

  • Essential for normal pregnancy; its deficiency may impair cervical ripening or delay labor.

  • High relaxin levels may contribute to pelvic girdle pain or joint laxity due to excessive ligament relaxation.

• Preterm labor prevention:

  • Due to its uterine relaxing effects, relaxin has been studied as a potential tocolytic agent, although with limited clinical use to date.

• Cardiovascular therapy:

  • Recombinant human relaxin (serelaxin) has been evaluated for treating acute heart failure due to its vasodilatory and anti-fibrotic properties, though clinical trial results are mixed.

• Fibrosis and tissue repair:

  • Experimental studies suggest relaxin could be useful in treating fibrotic conditions such as scleroderma, renal fibrosis, or pulmonary fibrosis.

• Male reproductive function:

  • In males, relaxin may influence sperm motility and seminal fluid quality, though clinical relevance is still under study.