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Cited by 90Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyStress Responses and Cortisol

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

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Uvnäs Moberg, Kerstin, Handlin, Linda, Kendall-Tackett, Kathleen, Petersson, Maria·2019·Medical Hypotheses
DOI 10.1016/j.mehy.2019.109394
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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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  • Oxytocin of peripheral and central origin may be released in parallel, and together the peripheral and central effects of oxytocin constitute the oxytocinergic system.

    “Oxytocin of peripheral and central origin may be released in parallel, and together the peripheral and central effects of oxytocin constitute the oxytocinergic system (Uvnäs Moberg et al., 2019).”

    From The Oxytocinergic System as a Mediator of Anti-stress and Instorative Effects Induced by Nature: The Calm and Connection Theory (2021) · cites this paper as Uvnäs Moberg et al., 2019

    The Chemical and morphological structure section describes oxytocin release into both the circulation and the brain, and Conclusion C1–2 says that during breastfeeding, oxytocin is released within the brain at the same time that its release into circulation is observed. The paper does not state that the peripheral and central effects together constitute the “oxytocinergic system.” Page numbers were not available in our copy. (LLM, conf=0.84)

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  • The pattern of effects sometimes differs substantially indicating that the two techniques may detect different variants of oxytocin.

    “Furthermore, the pattern of effects sometimes differs substantially indicating that the two techniques may detect different variants of oxytocin (Uvnäs Moberg et al., 2019, Uvnäs-Moberg et al., 2020a).”

    From The Oxytocinergic System as a Mediator of Anti-stress and Instorative Effects Induced by Nature: The Calm and Connection Theory (2021) · cites this paper as Uvnäs Moberg et al., 2019

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Cited by

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Authors
Uvnäs Moberg, K., Handlin, L., Kendall-Tackett, K., & Petersson, M.
Affiliations
  • University of Skövde (SE)
  • Texas Tech University (US)
  • Karolinska Institutet (SE)
Corresponding author
Handlin, Linda
ORCID
Venue
Medical Hypotheses
Publisher
Elsevier BV
Published
2019-12
Volume
133
Pages
109394
ISSN
0306-9877 (ISSN-L)
DOI
10.1016/j.mehy.2019.109394
OpenAlex
W2972302104
Cited by
90
References
8
Citations by year
2026: 7 · 2025: 11 · 2024: 12 · 2023: 13 · 2022: 20 · 2021: 14 · 2020: 13
FWCI
14.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Medical Hypotheses (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • University Library of Skövde (University of Skövde) (submittedVersion, other-oa)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
oxytocin, C-terminal fragment, alpha2-adrenoceptors, anti-stress effects, pain threshold, blood pressure, cortisol, social behavior, skin-to-skin contact, breastfeeding, blood-brain barrier, biphasic effect
MeSH terms
Animals, Anxiety, Brain, Female, Humans, Obstetric Labor, Premature, Lactation, Oxytocin, Pain, Peptide Fragments, Pregnancy, Protein Processing, Post-Translational, Social Behavior, Stress, Psychological, Uterine Contraction, Wound Healing, Tocolytic Agents, Receptors, Oxytocin, Rats

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