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Oxytocin is a principal hormone that exerts part of its effects by active fragments
Department of Animal Environment and Health, Swedish University of Agricultural Sciences, Skara, Sweden.ORCID iD: 0000-0003-4902-839X
University of Skövde, School of Health and Education. University of Skövde, Health and Education. (Translational Medicine TRIM)ORCID iD: 0000-0003-0987-8357
Texas Tech University School of Medicine, Amarillo, TX, USA.
Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet, Sweden.
2019 (English)In: Medical Hypotheses, ISSN 0306-9877, E-ISSN 1532-2777, Vol. 133, p. 1-9, article id 109394Article in journal (Refereed) Published
Abstract [en]

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. 

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 133, p. 1-9, article id 109394
National Category
Obstetrics, Gynecology and Reproductive Medicine Pharmacology and Toxicology Physiology Cell and Molecular Biology
Research subject
Translational Medicine TRIM
Identifiers
URN: urn:nbn:se:his:diva-17717DOI: 10.1016/j.mehy.2019.109394PubMedID: 31525634Scopus ID: 2-s2.0-85072083705OAI: oai:DiVA.org:his-17717DiVA, id: diva2:1353527
Available from: 2019-09-23 Created: 2019-09-23 Last updated: 2019-11-11Bibliographically approved

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Uvnäs-Moberg, KerstinHandlin, Linda

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