Effects of Oxytocin Outside Pregnancy

Lippert, T. H.; Mueck, Alfred O.; Seeger, Harald; Pfaff, Andreas

doi:10.1159/000074243

Cited by 31 publications

(26 citation statements)

References 66 publications

(74 reference statements)

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“…Studies have shown that OT is released into the circulation as a direct response to CS. This has been demonstrated in sheep (26), rats (36), and humans (the Ferguson reflex) (14,27,30). The main goal of this study is to determine whether a sustained PRL rhythm can be triggered by a single injection of OT.…”

mentioning

confidence: 92%

Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin

Egli¹,

Bertram²,

Toporikova³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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. Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin. Am J Physiol Endocrinol Metab 290: E566 -E572, 2006; doi:10.1152/ajpendo.00427.2005.-Mating or vaginocervical stimulation [copulatory stimulus (CS)] induces two daily surges of the hormone prolactin (PRL) in rats. This unique secretory pattern of PRL surges is characteristic for the first half of pregnancy and is also present in ovariectomized (OVX) rats. Studies have shown that CS additionally provokes an acute release of the hormone oxytocin (OT).In this study, we tested whether a single injection of OT (iv) is sufficient to initiate the PRL secretion pattern of OVX/CS rats. Furthermore, we measured the 24-h profile of dopamine (DA) content in the anterior lobe of the pituitary gland, because DA is the major inhibitory factor of PRL secretion. The results indicated that a single injection of OT induces a PRL secretory rhythm and a DA release pattern similar to that initiated by CS. Immunocytochemical investigation showed that particular OTergic neurons in the hypothalamus express receptors for PRL, as well as for vasoactive intestinal polypeptide, which indicates an involvement in generating the PRL rhythm and entraining it to the ambient photoperiod. On the basis of this study, we suggest that the PRL-DA inhibitory feedback loop between lactotrophs and DAergic neurons plays a crucial role in generating the oscillatory PRL secretion pattern in CS rats. A timing signal, likely provided by the hypothalamic suprachiasmatic nucleus, entrains the autonomous PRL oscillation to a particular time of day. Mathematical modeling was used to illustrate the proposed network function. The experimental results further suggest an additional feedback mechanism in which certain hypothalamic OTergic neurons are influenced by PRL. dopamine; suprachiasmatic nucleus; mathematical modeling; lactotrophs THE EARLY PHASE OF PREGNANCY and pseudopregnancy in rats is characterized by two daily peaks of prolactin (PRL) secretion, referred to as nocturnal (at ϳ0300) and diurnal (at ϳ1700) surges (13,15,21). This unique secretory pattern is induced by the mating stimulus or vaginocervical stimulation [copulatory stimulus (CS)] and persists for ϳ10 days in pregnant (45) animals and 12 days in pseudopregnant animals (44). The increased PRL output is important in maintaining the structural and functional integrity of the corpus luteum, which, in turn, is responsible for progesterone synthesis (44). The PRL secretory pattern in CS rats entrains to photoperiod and can be shifted within limits under various lighting conditions (53). Furthermore, this pattern becomes free running in constant darkness, which demonstrates that the PRL rhythm is a true circadian rhythm (6).PRL secretion from lactotrophs, located in the anterior lobe of the pituitary gland, is controlled by a balance of PRLreleasing and -inhibiting hormones supplied to the pituitary gland from neurosecretory cells in the hypothalamus through the portal vasculature (1,15,28). Several in vivo and in vi...

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mentioning

confidence: 92%

Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin

Egli¹,

Bertram²,

Toporikova³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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“…This response promotes affiliative and social behaviour in response to stressful circumstances (Boutet et al, 2006;Engelmann et al, 2004;Lippert et al, 2003), maximising fitness through care (or 'tending') of offspring or others during periods of stress. However, the relationship in which OT suppresses or attenuates stress response is neither straightforward nor universal.…”

Section: Oxytocin and Stressmentioning

confidence: 99%

Oxytocin and Epstein‐Barr virus: Stress biomarkers in the postpartum period among first‐time mothers from São Paulo, Brazil

Rudzik¹,

Breakey²,

Bribiescas

2013

American J Hum Biol

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Citation for published item:udzikD el nn iFpF nd fre keyD eli i nd fri ies sD i h rd qF @PHIRA 9yxyto in nd ipsteinEf rr virus X stress iom rkers in the postp rtum period mong (rstEtime mothers from £ o uloD fr zilF9D emeri n journ l of hum n iologyFD PT @IAF ppF RQESHF Further information on publisher's website:httpXGGdxFdoiForgGIHFIHHPG jh FPPRVW Publisher's copyright statement: his is the epted version of the following rti leX udzikD el nn iFpF nd fre keyD eli i nd fri ies sD i h rd qF @PHIRA 9yxyto in nd ipsteinEf rr virus X stress iom rkers in the postp rtum period mong (rstEtime mothers from £ o uloD fr zilF9D emeri n journ l of hum n iologyFD PT @IAF ppF RQESHD whi h h s een pu lished in (n l form t httpXGGdxFdoiForgGIHFIHHPG jh FPPRVWF his rti le m y e used for nonE ommer i l purposes in ord n e ith iley erms nd gonditions for selfE r hivingF Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. 2 AbstractObjectives: The purpose of the study was to examine the relationship between selfreported stress levels among new mothers in São Paulo, Brazil and two biomarkers of stressful experience, oxytocin (OT) and Epstein-Barr Virus antibody level (EBV-ab), with planned pregnancy hypothesised as a moderator of biological response to stressful conditions. Methods: Sixty-three first-time mothers between the ages of 15 and 45 were recruited from neighbourhoods in São Paulo, Brazil. Quantitative and qualitative data were collected longitudinally, bi-weekly between two and 12 weeks postpartum. OT level was assessed from breast milk samples and EBV-ab from blood spot samples. An Interpersonal Satisfaction scale was developed, validated and administered, along with the Cohen Perceived Stress Scale (PSS). Results:In-depth interview data revealed unplanned pregnancy to be a significant stressor in the lives of first-time mothers. In linear regression, OT level was negatively associated with Interpersonal Satisfaction score (p=.022) and positively associated with PSS score (p=.007). When splitting the sample by planned status of the pregnancy, women with an unplanned pregnancy showed a strengthened positive association between OT level and PSS (p=.001; Adj R 2 =0.44) and negative association with Interpersonal Satisfaction (p=.017; Adj R 2 =0.15), while no associations existed for women with a planned pregnancy. EBV-ab level was not correlated or associated with stress/satisfaction measures. Conclusion:OT is an effective biomarker in the measurement of stress in the body, and additionally reflects differential experiences with difficul...

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“…Within the periphery the OTR is localized in a number of different organs including the uterus and mammary glands. In the uterus it is involved in the onset and progression of labor and OT has been long regarded as a pregnancy hormone 20 as it stimulates labor and milk ejection.…”

Section: Structure and Function Of Ot And The Otrmentioning

confidence: 99%

The design of orally bioavailable 2, 5‐diketopiperazine oxytocin antagonists: from concept to clinical candidate for premature labor

Borthwick¹,

Liddle²

2011

Medicinal Research Reviews

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A short, efficient and highly stereoselective synthesis has been developed for a series of 6-indanyl-3-alkyl-7-aryl/heterocyclic-(3R, 6R, 7R)-2, 5-diketopiperazine amides that are potent and selective oxytocin (OT) antagonists. Property-based design using an estimate of human oral absorption enabled focus to be directed to those templates with the greatest chance of delivering high bioavailability in humans. This led to the 2', 4'-difluorophenyl dimethylamide 40, a highly potent (pK(i) =9.2) and selective OT antagonist (>1,000-fold selectivity vs. the human vasopressin receptors V1a, V2, and V1b) with good oral bioavailability (>50%) in the rat and dog. Increased solubility and an improved Cyp450 profile was achieved with a range of 2'-substituted 7-(1',3'-oxazol-4'-yl)-(3R,6R,7R)-2,5-diketopiperazine amides and branching at the α-carbon of the 3-butyl group led to a superior rat pharmacokinetic profile that resulted in the discovery of the 2'-methyl-1',3'-oxazol-4'-yl morpholine amide derivative 74 GSK221149A (Retosiban), which had the best oral exposure and bioavailability in the rat. Retosiban has sub-nanomolar affinity (K(i) =0.65 nM) for the oxytocin receptor with >1400-fold selectivity over the closely related vasopressin receptors. It has good solubility, low protein binding and has a good Cyp450 profile with no significant inhibition IC(50) >100 µM. Retosiban is >15-fold more potent at the human oxytocin receptor than atosiban (a marketed i.v, peptide OT antagonist) and it has been shown to be an effective tocolytic by i.v. and by oral administration in rats, and was selected for progression as a potential clinical candidate for preterm labor.

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Effects of Oxytocin Outside Pregnancy

Cited by 31 publications

References 66 publications

Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin

Prolactin secretory rhythm of mated rats induced by a single injection of oxytocin

Oxytocin and Epstein‐Barr virus: Stress biomarkers in the postpartum period among first‐time mothers from São Paulo, Brazil

The design of orally bioavailable 2, 5‐diketopiperazine oxytocin antagonists: from concept to clinical candidate for premature labor

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