Current Advances in Oxytocin Research

Dear Colleagues,

The discovery of the pituitary neurohormone oxytocin led to the 1955 Nobel Prize in Chemistry being awarded to Vincent du Vigneaud. This represented the culmination of a research programme dating back to 1895, when Oliver and Schafer reported that a substance extracted from the pituitary gland elevates blood pressure when intravenously injected into dogs. Dale later reported on a neurohypophysial substance that triggers uterine contraction, stimulates lactation and functions in antidiuresis. Purification of the pituitary gland extracts revealed that the vasopressor and antidiuretic activity could be attributed to vasopressin, and the uterotonic and lactation-promoting activity could be attributed to oxytocin. In 1950, the amino acid sequences of vasopressin and oxytocin were determined, and both peptides were chemically synthesised. This revealed that vasopressin (CYFQNCPRG-NH2) and oxytocin (CYIQNCPLG-NH2) are structurally very similar, with only two amino acids differing, which is indicative of their common evolutionary origin and a disulphide bridge between the cysteine residues at positions 1 and 6 conserved in all vasopressin/oxytocin-type peptides. This characterisation and discovery of oxytocin led to the Nobel Prize being awarded to Vincent du Vigneaud in 1955. The common evolutionary origin of vasopressin and oxytocin, as indicated by their structural similarity, dates back to millions of years ago, which suggests that oxytocin has effects that go beyond uterine contractions and pregnancy. Nevertheless, such evidence was uncovered only 50 years after its discovery, in early 2000, when mice depleted of either oxytocin or its receptor were observed to develop late onset obesity and metabolic syndrome, thus establishing the involvement of oxytocin in the regulation of energy and metabolism. Interestingly, the metabolic phenotype of oxytocin and oxytocin receptor-deficient mice diverges in young versus older animals, taking time to reach full force, and is established in the absence of hyperphagia. The effects of oxytocin on fat and energy are both direct, since oxytocin is anorexigenic, and indirect, when oxytocin regulates the lean/fat mass composition in skeletal muscle, potentiating the slow twitch muscle as it does in the uterus. Finally, while oxytocin negatively modulates adipogenesis, peripheral oxytocin promotes osteoblast differentiation and function, leading to increased bone formation through the direct effect of oxytocin binding to its receptor on osteoblasts. Connecting the dots downstream of these findings, it appears that oxytocin acts on the three components of body composition: fat, muscle and bone. Evolutionarily, the anabolic effect of oxytocin makes sense since oxytocin concentrations increase during challenging situations, including pregnancy and lactation in mammals, and triggers aggressive behaviour that, in females, is important for the protection of offspring after labour, when they are most vulnerable to predators, and plasma oxytocin concentration is at its peak. From a wider perspective, this demonstrates that the effects of oxytocin are beneficial in the management of osteoporosis, body fat gain, diabetes, sarcopenia and all age-related diseases affecting elderly men and women, indicating the exciting therapeutic potential but also challenges, namely, to find a single route, dosage and schedule able to reach all the targets. Thus, let this be a mission that could be celebrated in 2055, i.e., the 100th anniversary of oxytocin’s discovery. As such, for this Special Issue, we invite all colleagues that have made significant contributions to studies relating to oxytocin in recent years to contribute with reviews or original research articles.

Dr. Claudia Camerino
Guest Editor

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• oxytocin
• thermoregulation
• skeletal muscle
• obesity
• Prader–Willi syndrome