Regensburg, Univ., Diss., 2009.

Η Ωκυτοκίνη (ΟΤ) είναι ένα κυκλικό εννιαπεπτίδιο του υποθαλάμου, η οποία απελευθερώνεται στη γενική κυκλοφορία από τον οπίσθιο λοβό της υπόφυσης. Οι κύριες φυσιολογικές δράσης της είναι η επαγωγή συσπάσεων του μυομητρίου και η έκθλιψη του γάλακτος. Εν τούτοις, η μεγάλη διασπορά των υποδοχέων της ΟΤ στον εγκέφαλο αποδίδουν στην ορμόνη το ρόλο του νευροδιαβιβαστή, ο οποίο ρυθμίζει τις αναπαραγωγικές και κοινωνικές συμπεριφορές. Ο ρόλος της ΟΤ στην πρόκληση του πρόωρου τοκετού οδήγησε την έρευνα για το σχεδιασμό και τη σύνθεση πεπτιδικών ανταγωνιστών της ορμόνης ως δραστικούς τοκολυτικούς παράγοντες. Πλήθος τέτοιων αναλόγων συντέθηκε και εξετάστηκε, αλλά μόλις για ένα, το Atosiban, και μόνο στην Ευρώπη, επετράπη η κυκλοφορία για την πρόληψη του πρόωρου τοκετού με την εμπορική ονομασία Tractocile™. Ο σχεδιασμός νέων αναλόγων της ΟΤ βασίζεται στα συμπεράσματα δομής-δραστικότητας. Η ανταγωνιστική δράση εξαρτάται από τη διαμόρφωση και την υδροφοβικότητα του αμινοξέος στη θέση 2. Επιπρόσθετα, η απαλοιφή της τελικής αμινομάδας προσδίδει στο πεπτίδιο παράταση της δράσης. Ιδιαίτερη σημασία στην εκλεκτική πρόσδεση της ΟΤ στον υποδοχέα της έχει η Ιle στη θέση 3, μιας και είναι το μόνο αμινοξύ στο οποίο διαφέρει στον εικοσαμελή δακτύλιο η ΟΤ από το συγγενές μόριο της, τη Βασοπρεσίνη (VP). Βασιζόμενοι στα ανωτέρω συμπεράσματα και για διερεύνηση του ρόλου της θέσης 3 της ορμόνης, συνθέσαμε δεκατέσσερα νέα ανάλογα της ΟΤ. Όλα τα ανάλογα περιέχουν β-μερκαπτοπροπιονικό οξύ (Mpa) στη θέση 1 και D-O-αιθυλ-τυροσίνη [D-Tyr(Et)] ή D-1-ναφθυλ-αλανίνη [D-Nal(1)] στη θέση 2. Η ισολευκίνη (Ile) στη θέση 3 έχει υποκατασταθεί με γ-αμινοϊσοβουτυρικό οξύ (Aib), L- ή D-α-τερτβουτυλ-γλυκίνη [L-/D-Gly(But)], L- ή D-3-πυριδυλ-αλανίνη [L-/D-Pal(3)] και L- ή D-β-(2-θεϊενυλ)-αλανίνη (L-/D-Thi). Τα φάσματα μάζας των αναλόγων συμφωνούν με τα αναμενόμενα αποτελέσματα. Τα δεκατέσσερα ανάλογα εξετάστηκαν ως προς την ωκυτόκιο δράση σε απομονωμένο ιστό μήτρας αρουραίου, ως προς τη δράση επί της πίεσης και ως προς τη συγγένεια με τον ανθρώπινο ωκυτόκιο υποδοχέα. Επιπλέον, τα ανάλογα [Mpa1, D-Tyr(Et)2, Thi3]OT, [Mpa1, D-Tyr(Et)2, D- Thi3]OT], [Mpa1, D-Nal(1)2, Thi3]OT και [Mpa1, D-Nal(1)2, D- Thi3]OT] εξετάστηκαν και ως προς τη δράση τους επί του πολλαπλασιασμού των καρκινικών κυτταρικών σειρών MDA-MB-468 και MCF-7. Όλα τα ανάλογα δρουν ως ανταγωνιστές της φυσικής ορμόνης. Συγκεκριμένα, τα ανάλογα [Mpa1, D-Nal(1)2, Gly(But)3]OT και [Mpa1, D-Nal(1)2, Thi3]OT έχουν ισχυρή αντι-ωκυτόκιο δράση (pA2=8.34±0.30 και 8.50±0.24, αντίστοιχα). Όσο αφορά τα αποτελέσματα των βιολογικών δοκιμών επί του πολλαπλασιασμού των καρκινικών κυττάρων,αυτά δεν οδηγούν σε ασφαλή συμπεράσματα για τη δράση των αναλόγων. / Oxytocin (OT) is a cyclic nonapeptide hormone of hypothalamus that is released into the general circulation from the posterior lobe of the pituitary gland. Its major physiological roles are: a) the ability to induce uterine constructions and b) milk injection. However, widespread distribution of OT receptors in the brain and specific behavioral effects of centrally applied OT, have firmly established a role of OT as a neurotransmitter modulating reproductive and social behaviors. The role of OT in preterm labor led to the search for and design of synthetic peptide antagonists as potential tocolytic agents. A number of those OT analogues synthesized and studied. However, only Atosiban was approved, in Europe only, under the trade name Tractocile™ for the treatment of preterm labor. The design of new OT analogues is based on consequences from structure-activity studies. Antagonistic activity depends on the configuration and the hydrophobicity of the amino acid in position 2. Additionally, the deficiency of the amino-group in position 1 leads to prolongation of the activity. Furthermore, Ile3 is important for the selective binding of OT to its receptor. Based on these findings and for the investigation of the role of position 3 on biological activities, we synthesized by the Fmoc/But solid phase methodology fourteen new analogues of OT. All the analogues contain β-mercaptopropionic acid (Mpa) position 1 and D-O-ethyl-tyrosine [D-Tyr(Et)] or D-1-naphthyl-alanine [D-Nal(1)] in position 2. Isoleucine (Ile) in position 3 has substituted by γ-aminoisobutyric acid (Aib), L- or D-α-tertbutyl-glycine [L-/D-Gly(But)], L- or D-3-pyridyl-alanine [L-/D-Pal(3)] and L- or D-β-(2-thienyl)-alanine (L-/D-Thi). Electro-spray MS was in agreement with the expected results. The analogues were tested for uterotonic activity in the rat uterus in vitro test, for pressor activity in the rat pressor assay and for the affinity to human OT receptor using [3H]OT. Also, the analogues [Mpa1, D-Tyr(Et)2, Thi3]OT, [Mpa1, D-Tyr(Et)2, D- Thi3]OT], [Mpa1, D-Nal(1)2, Thi3]OT and [Mpa1, D-Nal(1)2, D- Thi3]OT] were tested for the activity on the proliferation of MDA-MB-468 and MCF-7 cells. All the new analogues are antagonists of the hormone. In particular, the analogues [Mpa1, D-Nal(1)2, Gly(But)3]OT and [Mpa1, D-Nal(1)2, Thi3]OT have potent anti-uterotonic activity (pA2=8.34±0.30 and 8.50±0.24, respectively). As regards the tests of proliferation, we are unable to come to a sfe conclusion as far as the activity of the analogues is concerned.

No description available.

The shock prod defensive burying test has proven incredibly reliable and instrumental in determining the underpinnings of normal anxiety in rodents. Largely ignored in tests of defensive burying, however, is the capacity for individual animals to display marked variations in active and passive coping behaviors. To unmask the neurobiological correlates of this behavioral differentiation, rats were exposed to a mousetrap that was remotely triggered upon approach to remove the quality of pain. This design invited striking variations in defensive burying behavior levels, in which some rats either buried robustly or showed little to no levels of defensive burying. Furthermore, differences in burying behavior were associated with marked differences in the central expression of arginine vasopressin (AVP) and oxytocin (OT). Thus, relative to animals showing no significant levels of defensive burying activity, rats showing sustained elevations in defensive burying expressed higher levels of AVP mRNA and increased numbers of androgen receptor positive cells in the medial amygdala and posterior bed nuclei of the stria terminalis, brain regions that integrate emotional appraisal and sensory information. In contrast, animals showing little to no defensive burying responses expressed relatively higher levels of AVP and OT mRNA within the supraoptic nucleus and subregions of the paraventricular nucleus of the hypothalamus responsible for neuroendocrine and autonomic function. CRH mRNA levels did not vary as a function of burying activity in the central nucleus of the amygdala, the anterior division of the bed nuclei of the stria terminalis, nor in the paraventricular nucleus. These findings suggest a role for central AVP and OT in mediating differential defensive behaviors, and demonstrate the utility of using a pain free test of conditioned defensive burying as a framework for exploring individual differences in behavioral coping and neuroendocrine capacity. / Medicine, Faculty of / Graduate

Soy based products are growing in popularity in food supplementation, and a larger population of the world is consuming soy on a regular basis. Soy contains phytoestrogens, plant based mimics of the hormone estrogen. Estrogen has many functions in humans, but one relatively unexplored function is its ability to regulate the levels of the hormone oxytocin (OT) and its receptor (OTR) in the brain. OT is a hormone traditionally known for its role in birth, but recently has been as a key regulator in many different behaviors. These behaviors that OT may affect include increased maternal behaviors, increased sexual behaviors, increased social interactions, increased trust, decreased anxiety, and increased potential for pair bonding. Key phytoestrogens found in soy are of the isoflavone family, and genistein and diadzein are the main two isoflavones that have been shown to exert physiologic effects when ingested by binding to estrogen receptors in the brain. The isoflavones can be estrogen agonists or estrogen antagonists, based on the preexisting, endogenous levels of estrogen in the individual. For men and postmenopausal women, it is believed that ingesting soy can cause an increase in production of OT and OTR, resulting in an increased in OT driven behaviors. For premenopausal women, there is a high endogenous level of estrogen present, so the ingested soy can cause a decrease in production of OT and OTR in the brain, resulting in a decrease in OT driven behaviors. While there is strong evidence to suggest that this may in fact occur in humans, more human based studies, rather than animal models, must be conducted to further verify and validate this hypothesis. An important area yet unexplored is the onset and duration of these OT driven behaviors. It is unclear if these are transient, or more long lasting effects, and future studies must be done to answer this question. This area of research is certainly more relevant as soy based diets are becoming more common; moving forward additional research is needed to determine the extent of oxytocin's ability to alter behaviors in individuals in a significant way.

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. The prefrontal cortex (PFC) is most susceptible to injury which leads to deficits in executive function, sociability, and cognitive flexibility. The oxytocin (OT) system plays a significant role in the modulation of species-typical social behaviors, such as social recognition and memory. Intranasal OT (IN-OT) has been shown to be neuroprotective against neuronal insults and social deficits through various mechanisms. Due to this and OT’s role in the modulation of social behaviors, it is possible that IN-OT could improve the social deficits caused by a PFC injury. The primary goal of this study was to determine the effects of a TBI on the development of the OT system. The secondary goal was to address the efficacy of IN-OT as a treatment for the social deficits observed following a TBI. For these studies, animals received a single cortical contusion injury bilaterally damaging the medial pre-frontal cortex. Immediately following injury (1-2 minutes), animals were given a single dose of IN-OT (20 μg, 1 μg/1 μl Ringer’s solution), placebo, or no treatment and sacrificed at days 1, 14, and 30 post-injury. Animals were assessed using behavioral and histological measures. It was predicted that animals that received IN-OT would demonstrate fewer social deficits on the behavioral measures and a smaller lesion size. Additionally, it was expected that a TBI would increase inflammation levels and decrease the levels of OT and OT receptors compared to sham animals. The results indicate that OT treatment did not significantly improve histopathological outcomes. However, the vehicle that was utilized impaired outcomes. Additionally, there was minimal changes to the OT system at the injury site, in the anterior olfactory nucleus, and in the caudate putamen due to injury. But vehicle treatment altered the expression levels of the OT peptide and receptors. Behaviorally, OT treatment improved performance in the Morris water maze in TBI animals compared to vehicle-treated and untreated TBI animals, but not other behaviors. However, vehicle-treated, and OT-treated animals were more likely to be aggressive than expected and untreated sham animals were less likely to be aggressive than expected. Taken together, it was observed that administration of a hypotonic saline solution following TBI significantly increases pathophysiology after TBI, and these effects translate into increased aggression levels. Although, learning and memory remained unaffected by the vehicle. Thus, further studies are needed to examine the effects of OT on TBI for behavioral and pathophysiological improvements.

Anxiety disorders pose a great burden onto society and economy and can have devastating consequences for affected individuals. Treatment options are still limited to psychopharmacotherapy originally developed for the treatment of depression and behavioral therapy. A combination of genetic traits together with aversive events is most likely the cause of these diseases. Gene x environment studies are trying to find a link between genetic traits and specific negative circumstances. In a first study, we focused on social anxiety disorder (SAD), which is the second most-common anxiety disorder after specific phobias. We used a social fear conditioning (SFC) paradigm, which is able to mimic the disease in a mouse model. We wanted to investigate protein levels, as well as mRNA expression of immediate early genes (IEGs), to determine brain areas affected by the paradigm. We also included genes of the vasopressin (AVP)-, oxytocin (OXT)-, neuropeptide Y (NPY)-, and the serotonin system, to investigate the effects of SFC on neurotransmitter gene expression levels in brain regions related to social as well as fear-related behavior. AVP and OXT regulate a lot of different social and anxiety-related behaviors, both positive and negative. Finding a link between different neurotransmitter systems in the development of anxiety disorders could help to identify potential targets for new treatment approaches, which are desperately needed, because the rate of patients not responding to available treatment is very high. We were able to show altered gene expression of the IEGs cFos and Fosl2, as well as a change in number and density of cFOS-positive cells in the dorsal hippocampus, indicating an influence of SFC on neuronal activity. Our results reveal a possible involvement of anterior dentate gyrus (DG), as well as cornu ammonis area 1 (CA1) and CA3 in the dorsal hippocampus during the expression of social fear. Contrary to our hypothesis, we were not able to see changes in neuronal activity through expression changes of IEGs in the amygdala. Significant higher IEG immunoreactivity and gene expression in the dorsal hippocampus of animals without fear conditioning (SFC-), compared to animals with fear conditioning (SFC+), indicate an involvement of different hippocampal regions in two possible scenarios. Either as elevated gene expression in SFC- animals compared to SFC+ animals or as reduction in SFC+ animals compared to SFC- animals. However, this question cannot be answered without an additional control of basal IEG-activity without social interaction. The NPY system in general and the neuropeptide y receptor type 2 in particular seem to be involved in regulating the response to social fear, mostly through the septum region. In addition to that, a possible role for the induction of social fear response could be identified in the serotonergic system and especially the serotonin receptor 2a of the PVN. In a second study we focused on changes in the serotonergic system. A polymorphism in the human serotonin transporter (5-HTT) gene is associated with higher risks for the development of anxiety disorders. This makes the 5-HTT a widely used target to study possible causes and the development of anxiety disorders. In mice, a genetically induced knockout of the 5-Htt gene is associated with increased anxiety-like behavior. High amounts of stress during pregnancy, also known as prenatal stress, significantly increase the risk to develop psychiatric disorders for the unborn child. We utilized a prenatal stress paradigm in mice heterozygous for the 5-Htt gene. Some of the animals which had been subjected to prenatal stress showed noticeably “unsocial” interaction behavior towards conspecifics. Again, we were searching for links between the serotonergic system and AVP- and OXT systems. Through quantitative gene expression analysis, we were able to show that both AVP and OXT neuromodulator systems are affected through prenatal stress in female mice, but not in male mice. The 5-Htt genotype seems to be only slightly influential to AVP, OXT or any other neurotransmitter system investigated. Gene expression of AVP and OXT brain systems is highly influenced through the estrous cycle stages of female mice. Additionally, we analyzed the AVP and OXT neuropeptide levels of mice with different 5-Htt genotypes and in both sexes, in order to see whether the production of AVP and OXT is influenced by 5-Htt genotype. On neuropeptide level, we were able to identify a sex difference for vasopressin-immunoreactive (ir) cells in the PVN, with male mice harboring significantly more positive cells than female mice. / Angsterkrankungen sind eine große Belastung für Gesellschaft und Wirtschaft und können verheerende Folgen für Betroffene haben. Behandlungsmöglichkeiten sind nach wie vor auf Psychopharmakotherapie, welche ursprünglich für die Behandlung von Depressionen entwickelt wurde, und Verhaltenstherapie beschränkt. Eine Kombination aus bestimmten genetischen Eigenschaften zusammen mit aversiven Lebensereignissen sind die wahrscheinlichste Ursache für die Entstehung dieser Erkrankungen. Gen x Umweltstudien versuchen dabei, Verbindungen zwischen genetischen Merkmalen und spezifischen negativen Ereignissen zu finden. In einer ersten Studie haben wir uns auf die soziale Phobie konzentriert, welche die zweithäufigste Angsterkrankung nach spezifischen Phobien ist. Wir haben ein soziales Furchtkonditionierungs-Paradigma (social fear conditioning, SFC), verwendet, welches in der Lage ist, die soziale Phobie im Tiermodell nachzustellen. Wir haben nach einer Verbindung zwischen dem serotonergen System und den zwei Systemen der Neuromodulatoren Vasopressin (AVP) und Oxytocin (OXT) gesucht. Diese Neuropeptide beeinflussen im Gehirn als Neuromodulatoren das Verhalten, und regulieren sowohl positive als auch negative Aspekte des Sozial- und Angstverhaltens. Eine gegenseitige Beeinflussung dieser Neurotransmittersysteme bei der Entstehung von Angsterkrankungen zu identifizieren könnte dabei helfen, potentielle Ziele für neue Behandlungsansätze zu finden. Diese werden dringend benötigt, da der prozentuale Anteil der Patienten, für die es keine wirksame Behandlung gibt, hoch ist. Wir haben Proteinebene und mRNA Expression von unmittelbar frühen Genen (immediate early genes, IEGs) analysiert, um zu ermitteln, in welchen Hirnregionen die neuronale Aktivität durch das Paradigma beeinflusst wird. Außerdem wurde in dieser Studie eine Untersuchung der Gene von AVP-, OXT-, Neuropeptid Y (NPY)-Systemen, sowie von Genen des serotonergen Transmissionssystems eingeschlossen. Damit sollten die Auswirkungen von SFC auf die Genexpression in Hirnregionen, die mit Sozial- sowie Angstverhalten in Verbindung stehen, ermittelt werden. Wir konnten sowohl eine veränderte Genexpression von verschiedenen IEGs wie cFos und Fosl2, als auch Veränderungen in Zahl und Dichte von cFOS-positiven Zellen feststellen, was einen Einfluss von SFC auf neuronale Aktivität andeutet. Unsere Ergebnisse offenbaren eine mögliche Beteiligung des Gyrus dentatus (DG), sowie der Cornu ammonis area 1 (CA1) und CA3 im dorsalen Hippocampus bei der Expression von sozialer Angst. Entgegen unseren Vermutungen waren in der Amygdala keine Veränderungen der neuronalen Aktivität durch Expressionsänderungen der IEGs nachzuweisen. Signifikant höhere IEG-Immunreaktivität und -Genexpression im dorsalen Hippocampus von Tieren ohne Furchtkonditionierung (SFC-) im Vergleich zu Tieren mit Furchtkonditionierung (SFC+) weisen auf zwei mögliche Szenarien hin. Entweder handelt es sich um eine verstärkte Expression in SFC--Tieren im Vergleich zu SFC+-Tieren, oder die Expression in SFC+-Tieren ist im Vergleich zu SFC--Tieren erniedrigt. Ohne eine zusätzliche Kontrolle der basalen mRNA Konzentration und des Proteinvorkommens der IEGs in einer Kontrollgruppe ohne soziale Interaktionsmöglichkeit kann diese Frage allerdings nicht beantwortet werden. Das NPY-System generell und der NPY-Rezeptor 2 im Speziellen scheinen in die Regulation der Reaktion auf soziale Angst involviert zu sein, und dies hauptsächlich im Septum. Zusätzlich konnte eine mögliche Rolle für das serotonerge System und insbesondere den Serotonin Rezeptor 2a im Nucleus paraventricularis (PVN) bei der Reaktion auf soziale Angst identifiziert werden. In einer zweiten Studie haben wir uns auf Veränderungen des serotonergen Systems konzentriert. Ein Polymorphismus im humanen Serotonintransporter Gen (5-HTT) konnte mit einem höheren Risiko für Angsterkrankungen assoziiert werden. Dies macht den 5-HTT zu einem weit verbreiteten Ziel zur Erforschung von möglichen Ursachen und der Entwicklung von Angsterkrankungen. In Mäusen ist ein gentechnisch induzierter knockout des 5-Htt Gens mit erhöhtem Angstverhalten assoziiert. Ein hohes Stresslevel während der Schwangerschaft, auch als pränataler Stress bekannt, erhöht das Risiko für spätere psychiatrische Erkrankungen des noch ungeborenen Kindes signifikant. In unserer Studie haben wir ein pränatales Stress-Paradigma in Mäusen mit einer Defizienz des 5-Htt Gens verwendet. In einer vorangegangenen Studie hatten sich bereits einige der Tiere, die pränatalem Stress ausgesetzt waren, in der Interaktion mit anderen Tieren auffällig „unsozial“ verhalten, bzw. geringes Sozialverhalten gezeigt. Wir haben erneut mithilfe von Genexpressionsstudien nach einer Verbindung zwischen dem serotonergen System und den AVP- und OXT-Systemen gesucht. Zusätzlich haben wir AVP und OXT in Mäusen mit verschiedenen 5-Htt Genotypen und in beiden Geschlechtern auf Neuropeptidebene analysiert, um zu sehen, ob die Produktion von AVP und OXT durch den 5-Htt Genotyp und das Geschlecht beeinflusst ist. Im Zuge der quantitativen Genexpressionsstudie konnten wir zeigen, dass die AVP- und OXT- Neuropeptidsysteme in weiblichen, aber nicht in männlichen Mäusen, durch Pränatalstress beeinflusst werden. Der 5-Htt Genotyp scheint AVP, OXT und andere untersuchte Neurotransmittersysteme nur geringfügig zu beeinflussen. In Weibchen ist die Genexpression von Oxt und Oxtr teilweise stark durch den Östruszyklus beeinflusst. Auf Neuropeptidebene konnten wir einen Geschlechterunterschied bzgl. der durchschnittlichen Anzahl AVP-positiver Zellen im PVN feststellen; männliche Tiere hatten signifikant mehr positive Zellen als weibliche Tiere.

Prostaglandin F2a (PGF2a), oxytocin and gonadotropin releasing hormone (GnRH) have been used in bulls, rams, boars, stallions or rodents to increase sperm numbers in the ejaculate. Improving sperm quantity in the canine ejaculate would benefit all assisted reproductive techniques used in this species. The purpose of the present study was to evaluate the effects of PGF2a, oxytocin and GnRH on canine ejaculate characteristics. Eight, mature, medium size (25-30 kg), mixed breed dogs were randomly assigned to one of four treatment groups (N=2 dogs each); each group received one treatment per week for four weeks. Treatments were assigned based on a Latin Square design. A two-week training period was used to acclimate the dogs to manual semen collection. Treatments were 0.1 mg/kg PGF2a 15 minutes prior to collection, 2.5 units/dog oxytocin 10 minutes prior to collection, 50 mg/dog GnRH 60 minutes prior to collection, or 1.0 ml of saline 30 minutes prior to collection. An evaluator that was blinded to treatment analyzed ejaculate characteristics. Samples were evaluated for semen volume, concentration of spermatozoa per milliliter, motility, morphology, total sperm number and total morphologically normal motile sperm number (TNMS). In addition, a subjective ease of collection score was assigned following each collection (Scale 1-9, 1 being easiest to manually ejaculate). Semen concentration, motility and morphology were not different between treatments. Semen volume was greater for dogs treated with PGF2a or oxytocin compared to saline. Total sperm number and TNMS were greater when dogs were treated with PGF2a compared to oxytocin, GnRH and saline (p<0.05). The subjective ease of collection score was lower for dogs receiving PGF2a compared to GnRH or saline (p<0.05). In summary, administration of PGF2a or oxytocin prior to semen collection increased semen volume and PGF2a increased total sperm number in the ejaculate of the dog. It did not appear that treatment with GnRH had an effect on semen parameters evaluated in this study. / Master of Science

The treatment of most cancers can still be considered inadequate despite the steady progress being made. A prime example of this issue is with epithelial ovarian cancers; this disease presents a significant issue, with a 5-year survival rate of 46% and a survival rate of 28% in patients that develop metastatic disease. Since ovarian cancer has such a high mortality rate, effective treatment modalities are necessary to prolong the quality of life after diagnosis. Psychosocial stress is related to the progression, proliferation, and migration in cancer patients, but the mechanisms of this relationship are not fully understood. The present in vitro study investigated the ability of oxytocin, a neuropeptide associated with social support, to attenuate the stress response. Catecholamines, a subclass of stress hormones, were used to simulate the stress induced inflammation process in ovarian cancer cells. To evaluate oxytocin’s capacity to attenuate the stress response, the ovarian cancer cell lines SKOV3, HEYA8, OVCAR8, and OV432 were separately treated with the presence or absence of catecholamines with the addition of oxytocin. Protein expression of the oxytocin receptor was investigated using a western blot protocol. Oxytocin receptor, oxytocin, and IL-6 mRNA expression was evaluated by quantitative PCR. Treatment with Oxytocin attenuated the inflammatory response resulting from catecholamine treatment. The oxytocin receptor gene and protein were present in each cell line, suggesting that oxytocin has an anti-inflammatory role in the tumor microenvironment in ovarian cancer patients. These results provide a mechanism by which social support, working through the release of oxytocin, promotes an anti-inflammatory process in ovarian cancer patients. This study may shed light into new pharmacological approaches for the treatment of ovarian cancer.

No description available.