The Long Way of Oxytocin from the Uterus to the Heart in 70 Years from Its Discovery

The research program on oxytocin started in 1895, when Oliver and Schafer reported that a substance extracted from the pituitary gland elevates blood pressure when injected intravenously into dogs. Dale later reported that a neurohypophysial substance triggers uterine contraction, lactation, and antidiuresis. Purification of this pituitary gland extracts revealed that the vasopressor and antidiuretic activity could be attributed to vasopressin, while uterotonic and lactation activity could be attributed to oxytocin. In 1950, the amino-acid sequences of vasopressin and oxytocin were determined and chemically synthesized. Vasopressin (CYFQNCPRG-NH(2)) and oxytocin (CYIQNCPLG-NH(2)) differ by two amino acids and have a disulfide bridge between the cysteine residues at position one and six conserved in all vasopressin/oxytocin-type peptides. This characterization of oxytocin led to the Nobel Prize awarded in 1955 to Vincent du Vigneaud. Nevertheless, it was only 50 years later when the evidence that mice depleted of oxytocin or its receptor develop late-onset obesity and metabolic syndrome established that oxytocin regulates energy and metabolism. Oxytocin is anorexigenic and regulates the lean/fat mass composition in skeletal muscle. Oxytocin’s effect on muscle is mediated by thermogenesis via a pathway initiated in the myocardium. Oxytocin involvement in thermogenesis and muscle contraction is linked to Prader-Willi syndrome in humans, opening exciting therapeutic avenues.