Oxytocin is a principal hormone that exerts part of its effects by active fragments

Abstract

Oxytocin is a nonapeptide consisting of a cyclic six amino-acid structure and a tail of three amino acids. It was originally known for its ability to induce milk ejection and to stimulate uterine contractions. More recently, oxytocin has been shown to stimulate social behaviors, and exert pain-relieving, anti-stress/anti-inflammatory and restorative effects. We hypothesize that oxytocin is a principal hormone that, in part, exerts its effects after degradation to active fragments with more specific effect profiles. Experimental findings on rats show that administered oxytocin exerts biphasic effects. For example, after an initial increase in pain threshold, a second more long-lasting increase follows. Blood pressure and cortisol levels initially increase and then reverse into a long-lasting decrease in blood pressure and cortisol. Whereas the initial effects are, the second-phase effects are not blocked by an oxytocin antagonist, but by an opioid mu-antagonist and by an alpha 2-adrenoreceptor antagonist, respectively, suggesting that other receptors are involved. Repeated administration of oxytocin induces multiple anti-stress effects, which are mediated by alpha 2-adrenoreceptors. Repeated administration of linear oxytocin and linear oxytocin fragments with a retained C-terminal reduce spontaneous motor activity, a sedative or anti-stress effect, suggesting that alpha 2-adrenoreceptors have been activated. In contrast, linear mid-fragments stimulate motor activity. Low-intensity stimulation of cutaneous nerves in rats, as well as breastfeeding and skin-to-skin contact between mothers and babies, trigger immediate anti-stress effects. Some of these effects are likely caused by open ring/linear C-terminal fragments activating alpha 2-adrenoreceptors. Oxytocin fragments may be pre-formed and released in the brain or created by metabolic conversion of the principal hormone oxytocin in the central nervous system. Oxytocin and its fragments may also be released from peripheral sites, such as peripheral nerves, the gastrointestinal tract, and blood vessels in response to decreased sympathetic or increased parasympathetic nervous tone. Smaller fragments of oxytocin produced in the periphery may easily pass the blood-brain barrier to induce effects in the brain. In conclusion, oxytocin is linked to many different, sometimes opposite effects. The intact cyclic molecule may act to initiate social interaction and associated psychophysiological effects, whereas linear oxytocin and C-terminal fragments may induce relaxation and anti-stress effects following social interaction. In this way, the principal hormone oxytocin and its fragments may take part in a behavioral sequence, ranging from approach and interaction to calm and relaxation. Linear fragments, with an exposed cysteine-residue, may exert anti-inflammatory and antioxidant effects and thereby contribute to the health-promoting effects of oxytocin.

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