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Current Advances in Oxytocin Research

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 15730

Special Issue Editor

Dr. Claudia Camerino

E-Mail Website
Guest Editor
Department of Biomedical Sciences and Human Oncology (Section of Pharmacology), School of Medicine, University of Bari Aldo Moro, P.za G. Cesare 11, 70100 Bari, Italy
Interests: oxytocin; thermoregulation; skeletal muscle; obesity; Prader–Willi syndrome
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Special Issue Information

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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Keywords

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

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Published Papers (8 papers)

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Editorial

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2 pages, 148 KiB  
Editorial
Editorial for Special Issue “Current Advances in Oxytocin Research”
by Claudia Camerino
Curr. Issues Mol. Biol. 2025, 47(5), 363; https://doi.org/10.3390/cimb47050363 - 15 May 2025
Viewed by 107
Abstract
Very few hormones and neurotransmitters are as fascinating as oxytocin [...] Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)

Research

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31 pages, 2449 KiB  
Article
Sympathetic Innervation of Interscapular Brown Adipose Tissue Is Not a Predominant Mediator of Oxytocin-Induced Brown Adipose Tissue Thermogenesis in Female High Fat Diet-Fed Rats
by Andrew D. Dodson, Adam J. Herbertson, Mackenzie K. Honeycutt, Ron Vered, Jared D. Slattery, Matvey Goldberg, Edison Tsui, Tami Wolden-Hanson, James L. Graham, Tomasz A. Wietecha, Kevin D. O’Brien, Peter J. Havel, Carl L. Sikkema, Elaine R. Peskind, Thomas O. Mundinger, Gerald J. Taborsky, Jr. and James E. Blevins
Curr. Issues Mol. Biol. 2024, 46(10), 11394-11424; https://doi.org/10.3390/cimb46100679 - 15 Oct 2024
Cited by 2 | Viewed by 3400
Abstract
Recent studies have indicated that hindbrain [fourth ventricle (4V)] administration of the neurohypophyseal hormone, oxytocin (OT), reduces body weight, energy intake and stimulates interscapular brown adipose tissue temperature (TIBAT) in male diet-induced obese (DIO) rats. What remains unclear is whether chronic [...] Read more.
Recent studies have indicated that hindbrain [fourth ventricle (4V)] administration of the neurohypophyseal hormone, oxytocin (OT), reduces body weight, energy intake and stimulates interscapular brown adipose tissue temperature (TIBAT) in male diet-induced obese (DIO) rats. What remains unclear is whether chronic hindbrain (4V) OT can impact body weight in female high fat diet-fed (HFD) rodents and whether this involves activation of brown adipose tissue (BAT). We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of interscapular brown adipose tissue (IBAT) contributes to its ability to activate BAT and reduce body weight in female high HFD-fed rats. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of body weight in DIO rats. We first measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (0.5, 1, and 5 µg ≈ 0.5, 0.99, and 4.96 nmol) to stimulate TIBAT in female HFD-fed rats. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) stimulated TIBAT similarly between sham rats and denervated rats (p = NS). We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day ≈ 16.1 μg/day) or vehicle infusion to reduce body weight, adiposity and energy intake in female HFD-fed rats (N = 7–8/group). Chronic 4V OT reduced body weight gain (sham: −18.0 ± 4.9 g; denervation: −15.9 ± 3.7 g) and adiposity (sham: −13.9 ± 3.7 g; denervation: −13.6 ± 2.4 g) relative to vehicle treatment (p < 0.05) and these effects were similar between groups (p = NS). These effects were attributed, in part, to reduced energy intake evident during weeks 2 (p < 0.05) and 3 (p < 0.05). To test whether these results translate to other female rodent species, we also examined the effect of chronic 4V infusion of OT on body weight and adiposity in two strains of female HFD-fed mice. Similar to what we found in the HFD-fed rat model, we also found that chronic 4V OT (16 nmol/day) infusion resulted in reduced body weight gain, adiposity and energy intake in female DIO C57BL/6J and DBA/2J mice (p < 0.05 vs. vehicle). Together, these findings suggest that (1) sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and weight loss in female HFD-fed rats and (2) the effects of OT to reduce weight gain and adiposity translate to other female mouse models of diet-induced obesity (DIO). Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
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14 pages, 1765 KiB  
Article
Oxytocin Exhibits Neuroprotective Effects on Hippocampal Cultures under Severe Oxygen–Glucose Deprivation Conditions
by Mara Ioana Ionescu, Ioana-Florentina Grigoras, Rosana-Bristena Ionescu, Diana Maria Chitimus, Robert Mihai Haret, Bogdan Ianosi, Mihai Ceanga and Ana-Maria Zagrean
Curr. Issues Mol. Biol. 2024, 46(6), 6223-6236; https://doi.org/10.3390/cimb46060371 - 19 Jun 2024
Cited by 3 | Viewed by 1840
Abstract
Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen–glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may [...] Read more.
Perinatal asphyxia (PA) and hypoxic-ischemic encephalopathy can result in severe, long-lasting neurological deficits. In vitro models, such as oxygen–glucose deprivation (OGD), are used experimentally to investigate neuronal response to metabolic stress. However, multiple variables can affect the severity level of OGD/PA and may confound any measured treatment effect. Oxytocin (OXT) has emerged as a potential neuroprotective agent against the deleterious effects of PA. Previous studies have demonstrated OXT’s potential to enhance neuronal survival in immature hippocampal cultures exposed to OGD, possibly by modulating gamma-aminobutyric acid-A receptor activity. Moreover, OXT’s precise impact on developing hippocampal neurons under different severities of OGD/PA remains uncertain. In this study, we investigated the effects of OXT (0.1 µM and 1 µM) on 7-day-old primary rat hippocampal cultures subjected to 2 h OGD/sham normoxic conditions. Cell culture viability was determined using the resazurin assay. Our results indicate that the efficacy of 1 µM OXT treatment varied according to the severity of the OGD-induced lesion, exhibiting a protective effect (p = 0.022) only when cellular viability dropped below 49.41% in non-treated OGD cultures compared to normoxic ones. Furthermore, administration of 0.1 µM OXT did not yield significant effects, irrespective of lesion severity (p > 0.05). These findings suggest that 1 µM OXT treatment during OGD confers neuroprotection exclusively in severe lesions in hippocampal neurons after 7 days in vitro. Further research is warranted to elucidate the mechanisms involved in OXT-mediated neuroprotection. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
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Review

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14 pages, 316 KiB  
Review
The Role of the Arcuate Nucleus in Regulating Hunger and Satiety in Prader-Willi Syndrome
by Charlotte Höybye and Maria Petersson
Curr. Issues Mol. Biol. 2025, 47(3), 192; https://doi.org/10.3390/cimb47030192 - 14 Mar 2025
Viewed by 936
Abstract
Prader-Willi syndrome (PWS) is a rare genetic disorder. The main characteristics are muscular hypotonia, failure to thrive and feeding problems in infancy, which switch to hyperphagia in early childhood and continue into adulthood. Due to hyperphagia, the risk of developing morbid obesity is [...] Read more.
Prader-Willi syndrome (PWS) is a rare genetic disorder. The main characteristics are muscular hypotonia, failure to thrive and feeding problems in infancy, which switch to hyperphagia in early childhood and continue into adulthood. Due to hyperphagia, the risk of developing morbid obesity is high without treatment. PWS is considered a hypothalamic disease, and within the hypothalamus the arcuate nucleus (AC) is of central importance for controlling metabolism, hunger, and satiety. The AC has been studied in several animal models as well as in humans, including PWS. The function of AC is regulated by several neuropeptides and proteins produced within the central nervous system such as oxytocin, orexin, tachykinins as well as the hypothalamic hormones, regulating the adeno-hypophyseal hormones, also acting as neurotransmitters. Additionally, there are many peripheral hormones among which insulin, leptin, adiponectin, ghrelin, and glucagon-like peptide (GLP-1) are the most important. High levels of adiponectin and ghrelin have consistently been reported in PWS, but dysregulation and deviating levels of many other factors and hormones have also been demonstrated in both individuals with PWS and in animal models. In this review, we focus on the role of AC and peptides and proteins produced within the central nervous system in the regulation of hunger and satiety in PWS. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
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13 pages, 261 KiB  
Review
The Dynamicity of the Oxytocin Receptor in the Brain May Trigger Sensory Deficits in Autism Spectrum Disorder
by Claudia Camerino
Curr. Issues Mol. Biol. 2025, 47(1), 61; https://doi.org/10.3390/cimb47010061 - 17 Jan 2025
Viewed by 1398
Abstract
Sensory processing abnormalities have been noted since the first clinical description of autism in 1940. However, it was not until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 that sensory challenges were considered [...] Read more.
Sensory processing abnormalities have been noted since the first clinical description of autism in 1940. However, it was not until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 that sensory challenges were considered as symptoms of autism spectrum disorder (ASD). Multisensory processing is of paramount importance in building a perceptual and cognitive representation of reality. For this reason, deficits in multisensory integration may be a characteristic of ASD. The neurohormone oxytocin (Oxt) is involved in the etiology of ASD, and there are several ongoing clinical trials regarding Oxt administration in ASD patients. Recent studies indicate that Oxt triggers muscle contraction modulating thermogenesis, while abnormal thermoregulation results in sensory deficits, as in ASD. Activation of the Oxt system through exposure to cold stress regulates the expression of oxytocin receptor (Oxtr) in the brain and circulating Oxt, and if this mechanism is pathologically disrupted, it can lead to sensory processing abnormalities since Oxt acts as a master gene that regulates thermogenesis. This review will describe the sensory deficits characteristic of ASD together with the recent theories regarding how the modulation of Oxt/Oxtr in the brain influences sensory processing in ASD. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
25 pages, 4179 KiB  
Review
Oxytocin, the Love Hormone, in Stem Cell Differentiation
by Luca Pampanella, Giovannamaria Petrocelli, Federica Forcellini, Sara Cruciani, Carlo Ventura, Provvidenza Maria Abruzzo, Federica Facchin and Silvia Canaider
Curr. Issues Mol. Biol. 2024, 46(11), 12012-12036; https://doi.org/10.3390/cimb46110713 - 25 Oct 2024
Viewed by 1410
Abstract
Oxytocin (OXT) is a neurohypophysial nonapeptide that exerts its effects mainly through the oxytocin receptor (OXTR). Several studies have pointed out the role of OXT in the modulation of stem cell (SC) fate and properties. SCs are undifferentiated cells characterized by a remarkable [...] Read more.
Oxytocin (OXT) is a neurohypophysial nonapeptide that exerts its effects mainly through the oxytocin receptor (OXTR). Several studies have pointed out the role of OXT in the modulation of stem cell (SC) fate and properties. SCs are undifferentiated cells characterized by a remarkable ability to self-renew and differentiate into various cell types of the body. In this review, we focused on the role of OXT in SC differentiation. Specifically, we summarize and discuss the scientific research examining the effects of OXT on mesodermal SC-derived lineages, including cardiac, myogenic, adipogenic, osteogenic, and chondrogenic differentiation. The available studies related to the effects of OXT on SC differentiation provide little insights about the molecular mechanism mediated by the OXT–OXTR pathway. Further research is needed to fully elucidate these pathways to effectively modulate SC differentiation and develop potential therapeutic applications in regenerative medicine. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
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Graphical abstract

13 pages, 316 KiB  
Review
Is Oxytocin a Contributor to Behavioral and Metabolic Features in Prader–Willi Syndrome?
by Maria Petersson and Charlotte Höybye
Curr. Issues Mol. Biol. 2024, 46(8), 8767-8779; https://doi.org/10.3390/cimb46080518 - 13 Aug 2024
Cited by 2 | Viewed by 1491
Abstract
Prader–Willi Syndrome (PWS) is a rare genetic disorder typically characterized by decreased social interaction, hyperphagia, poor behavioral control and temper tantrums, together with a high risk of morbid obesity unless food intake is controlled. The genetic defects that cause PWS include paternal 15q [...] Read more.
Prader–Willi Syndrome (PWS) is a rare genetic disorder typically characterized by decreased social interaction, hyperphagia, poor behavioral control and temper tantrums, together with a high risk of morbid obesity unless food intake is controlled. The genetic defects that cause PWS include paternal 15q deletion (estimated in 60% of cases), chromosome 15 maternal uniparental disomy (UPD) (estimated in 35% of cases) and imprinting defects and translocations. Several studies indicate an oxytocin deficiency in PWS. Oxytocin is a hypothalamic nonapeptide with receptors located in the brain and in various other tissues in the body. It acts as a neuropeptide in several brain areas of great importance for behavioral and metabolic effects, as well as a neurohypophyseal hormone released into the circulation. Oxytocin in both rats and humans has strong and long-lasting behavioral and metabolic effects. Thus, an oxytocin deficiency might be involved in several of the behavioral and metabolic symptoms characterizing PWS. Treatment with oxytocin has, in some studies, shown improvement in psycho-social behavior and hyperphagia in individuals with PWS. This review focus on the behavioral and metabolic effects of oxytocin, the symptoms of a potential oxytocin deficiency in PWS and the effects of oxytocin treatment. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
19 pages, 481 KiB  
Review
The Role of Oxytocin in Polycystic Ovary Syndrome: A Systematic Review
by Nicoletta Cera, Joana Pinto and Duarte Pignatelli
Curr. Issues Mol. Biol. 2024, 46(6), 5223-5241; https://doi.org/10.3390/cimb46060313 - 25 May 2024
Cited by 3 | Viewed by 4003
Abstract
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age, representing the primary cause of anovulatory infertility. The nonapeptide oxytocin (OT) plays an important role in cognitive, emotional, and reproductive functions in human beings. Oxytocin receptors are [...] Read more.
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age, representing the primary cause of anovulatory infertility. The nonapeptide oxytocin (OT) plays an important role in cognitive, emotional, and reproductive functions in human beings. Oxytocin receptors are expressed in several body parts, including the ovaries. Despite this, the possible role played by oxytocin in symptoms of PCOS is not clear. The present systematic review aimed at understanding the presence of possible oxytocin level alterations in PCOS, the connection between alterations of OT levels and the symptoms of PCOS, and the effect of oxytocin administration in PCOS. After a systematic search in the principal databases, eight studies, five human and three animal, were included. Four human studies and one animal study highlighted the role played by oxytocin in fertility issues related to PCOS. Three human and two animal studies investigated the role of body weight and OT levels. Studies that analyzed oxytocin basal levels in women agreed that PCOS is associated with a reduction in the serum level of oxytocin. Two human studies and one animal study agreed about lower levels of oxytocin, confirming a possible implication of the dysfunction of OT in the pathogenesis of PCOS. Full article
(This article belongs to the Special Issue Current Advances in Oxytocin Research)
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