Basal Oxytocin Concentrations Research Articles

The salience of competing nonsocial objects reduces gaze toward social stimuli, but not the eyes, more in typically developing than autistic boys.

Decreased attention to social information is considered an early emerging symptom of autism spectrum disorder (ASD), although the underlying causes remain controversial. Here we explored the impact of nonsocial object salience on reduced attention to social stimuli in male ASD compared with typically developing (TD) children. Correlations with blood concentrations of neuropeptides linked with social cognition were also investigated. Eye-tracking was performed in 102 preschool-aged boys (50 ASD, 52 TD) using a paradigm with social (faces) versus nonsocial (objects) stimuli presented in pairs in two conditions where nonsocial stimulus salience was varied. Basal oxytocin (OXT) and vasopressin concentrations were measured in blood. Compared with TD boys those with ASD viewed social stimuli less only when they were paired with low-salience nonsocial objects. Additionally, boys with ASD spent less time than TD ones viewing facial features, particularly the eyes. In TD boys, OXT concentrations and cognitive development scores were positively associated with time spent viewing the eye region, whereas for boys with ASD associations with time spent viewing faces were negative. Reduced gaze toward social stimuli in ASD relative to TD individuals may therefore be influenced by how salient the paired nonsocial objects are for the latter. On the other hand, reduced interest in the eyes of faces in boys with ASD is not influenced by how salient competing nonsocial stimuli are. Basal OXT concentrations and cognitive development scores are predictive of time spent viewing social stimuli in TD boys (eyes) and those with ASD (faces) but in the opposite direction. LAY SUMMARY: Children with autism exhibit reduced attention to social paired with nonsocial stimuli compared to typically developing children. Using eye-tracking we show this difference is due to typically developing rather than autistic boys being more influenced by how interesting competing nonsocial objects are. On the other hand, reduced time looking at the eyes in autistic relative to typically developing boys is unaffected by nonsocial object salience. Time spent viewing social stimuli is associated with cognitive development and blood levels of oxytocin.

Oxytocin increases the pleasantness of affective touch and orbitofrontal cortex activity independent of valence

Touch plays a crucial role in affiliative behavior and social communication. The neuropeptide oxytocin is released in response to touch and may act to facilitate the rewarding effects of social touch. However, no studies to date have determined whether oxytocin facilitates behavioral or neural responses to non-socially administered affective touch and possible differential effects of touch valence. In a functional MRI experiment using a randomized placebo-controlled, within-subject design in 40 male subjects we investigated the effects of intranasal oxytocin (24IU) on behavioral and neural responses to positive, neutral and negative valence touch administered to the arm via different types of materials at a frequency aimed to optimally stimulate C-fibers. Results showed that oxytocin significantly increased both the perceived pleasantness of touch and activation of the orbitofrontal cortex independent of touch valence. The effects of OT on touch-evoked orbitofrontal activation were also positively associated with basal oxytocin concentrations in blood. Additionally, anterior insula activity and the functional connectivity between the amygdala and right anterior insula were enhanced only in response to negative valence touch. Overall, the present study provides the first evidence that oxytocin may facilitate the rewarding effects of all types of touch, irrespective of valence.

Peripheral oxytocin is inversely correlated with cognitive, but not emotional empathy in schizophrenia.

Endogenous oxytocin has been associated with different aspects of social cognition in healthy subjects and patients with schizophrenia. In this pilot study, we investigated the relationship between plasma oxytocin and oxytocin level changes induced by empathy-eliciting, attachment-related movie scenes with correlates of cognitive and emotional empathy in patients and healthy controls. The Multifaceted Empathy Test (MET) and the Interpersonal Reactivity Index (IRI) were administered to patients with schizophrenia (N = 35, 12 females) and healthy controls (N = 35, 12 females) to estimate dimensions of cognitive and emotional empathy. Peripheral basal oxytocin concentrations and oxytocin responses to movie-based emotional stimuli were assessed using radioimmunoassay with sample extraction. In patients, induced oxytocin level changes were inversely correlated with MET cognitive empathy regarding negative emotional states. Controlling for non-social cognition and age revealed a significant negative association between basal oxytocin levels and MET cognitive empathy for positive emotions. In healthy subjects, oxytocin reactivity was inversely correlated with the IRI subscale “fantasy”. Oxytocin was not related to any measure of emotional empathy. A hyper-reactive oxytocin system might be linked to impaired cognitive empathy as a part of a dysfunctional regulative circuit of attachment-related emotions and interpersonal stressors or threats by attribution of meaning. Healthy adults with a disposition to identify with fictional characters showed lower oxytocin reactivity, possibly indicating familiarity with movie-based stimuli. The oxytocinergic system may be involved in maladaptive coping mechanisms in the framework of impaired mentalizing and associated dysfunctional responses to interpersonal challenges in schizophrenia.

Luteal peptides and intercellular communication

The variety of peptides synthesized by the corpus luteum (relaxin, vasopressin, oxytocin and oxytocin-related neurophysin) and their possible intracellular effects are reviewed. After luteinization of the granulosa cells and in response to LH and FSH, the output of oxytocin is increased. In addition, insulin-like growth factor is a very potent stimulus of oxytocin secretion. Although luteal cells respond to gonadotrophins by increased production of progesterone, there is no further secretion of oxytocin. Oxytocin is localized in large luteal cells which seem not to be under the direct control of gonadotrophins. Synthesis of luteal oxytocin seems to occur during the early luteal phase according to measurements of oxytocin mRNA. Highest tissue concentrations and secretion under in-vitro conditions were observed during the mid-luteal phase, and so synthesis, storage and secretion are unlikely to occur concomitantly. Under in-vitro conditions, oxytocin is secreted concomitantly with neurophysin and progesterone, and there appears to be some form of communication between small and large luteal cells for the secretion of progesterone and oxytocin under in-vivo conditions. Evidence has been obtained that oxytocin may have local effects in the ovary by inhibition of secretion (synthesis ?) of progesterone, especially during the early luteal phase. A mechanism can be suggested whereby, under physiological conditions, oxytocin may delay the increase of progesterone by inhibition of progesterone secretion and therefore delay down regulation of its own receptor. This would prolong the life-span of the CL and the oestrous cycle. Exogenous progesterone given on Days 1-4 shortens the cycle to about 12 days. The best evidence that oxytocin may be involved in controlling luteolysis comes from immunization experiments in ewes and goats, but there is no clear evidence of this type for cattle. Basal concentrations of oxytocin at the end of the luteal phase may interact with oxytocin receptors after the inhibitory effect of progesterone in the uterus is reduced, thus initiating synthesis of PGF-2 alpha.

Foot massage evokes oxytocin release and activation of orbitofrontal cortex and superior temporal sulcus

Massage may be an important method for increasing endogenous oxytocin concentrations and of potential therapeutic benefit in disorders with social dysfunction such as autism where basal oxytocin levels are typically reduced. Here we investigated oxytocin release and associated neural responses using functional near infrared spectroscopy (fNIRS) during hand- or machine-administered massage. 40 adult male subjects received 10 min of light foot massage either by hand or machine in a counterbalanced order and then rated pleasure, intensity, arousal and how much they would pay for the massage. Blood samples were taken before and after each massage condition to determine plasma oxytocin concentrations. Neural responses from medial and lateral orbitofrontal cortex, superior temporal sulcus and somatosensory cortex were measured (fNIRS oxy-Hb) together with skin conductance responses (SCR), ratings of the massage experience, autistic traits and sensitivity to social touch. Results showed subjects gave higher ratings of pleasure, but not intensity or arousal, after hand- compared with machine-administered massage and there were no differential effects on SCR. Subjects were also willing to pay more for the hand massage. Plasma oxytocin increased after both massage by hand or machine, but more potently after massage by hand. Both basal oxytocin concentrations and increases evoked by hand-, but not machine-administered massage, were negatively associated with trait autism and attitudes towards social touch, but massage by hand-evoked changes were significant in higher as well as lower trait individuals. Increased neural responses to hand vs. machine-administered massage were found in posterior superior temporal sulcus and medial/lateral orbitofrontal cortex but not somatosensory cortex. Orbitofrontal cortex and superior temporal cortex activation during hand massage was associated with the amount of money subjects were willing to pay and between orbitofrontal cortex activation and autism scores. Thus, hand-administered massage can potently increase oxytocin release and activity in brain regions involved in social cognition and reward but not sensory aspects of affective touch. Massage by hand induced changes in both oxytocin concentrations and neural circuits involved in processing social affective trust may have therapeutic potential in the context of autism.

Effect of residual endogenous insulin secretion on the abnormal oxytocin response to hypoglycaemia in insulin‐dependent diabetes

Abstract. Volpi R, Chiodera P, Capretti L, Caffarri G, Giuliani N, Caiazza A, Coiro V (University of Parma, Hospital of Codogno, Hospital of Guastalla, Hospital of Fidenza, Italy). Effect of residual endogenous insulin secretion on the abnormal oxytocin response to hypoglycaemia in insulin‐dependent diabetics. J Intern Med 1998; 244: 43–8.ObjectivesArginine‐vasopressin (AVP) and oxytocin (OT) secretions are abnormally stimulated by hypoglycaemia in patients with IDDM. Since previous studies showed that AVP secretion is influenced by the persistence of residual endogenous insulin secretion, we wondered whether this factor also regulates OT secretion.DesignCase‐control study: the OT response to insulin‐induced hypoglycaemia was measured in normal and diabetic patients with or without residual endogenous insulin secretion.SubjectsTen normal male subjects, 10 C‐peptide positive (CpP) and 11 C‐peptide negative (CpN) male diabetic patients.TestsPreliminary studies: plasma C‐peptide levels were measured after intravenous administration of 1 mg glucagon.Insulin tolerance test (ITT): diabetics were studied after optimization of their metabolic status by 3 days of treatment with constant subcutaneous insulin infusion. CpP and CpN diabetics and normal controls were tested with an intravenous administration of 0.15 IU per kg body weight insulin. Blood samples for OT assay were taken just before the rapid injection of insulin (time 0) and at time 15, 30, 45 and 60 min.ResultsThe basal concentrations of OT were similar in all groups. Insulin induced a similar hypoglycaemic nadir in all groups at 30 min, even though diabetic groups showed a delayed recovery in blood glucose levels. The glycaemic pattern was similar in all diabetic patients. Hypoglycaemia‐induced OT rise was significantly higher in the two diabetic groups than in the normal group. However, CpN patients showed significantly higher OT increments than CpP subjects.ConclusionsThese data indicate that a residual endogenous insulin secretion exerts a partial protective action against the hypothalamic‐pituitary disorder affecting the OT secretory system in IDDM.

Intracerebroventricular injection of choline increases plasma oxytocin levels in conscious rats

In the present study, we examined the effect of intracerebroventricularly (i.c.v.) injected choline on both basal and stimulated oxytocin release in conscious rats. I.c.v. injection of choline (50–150 μg) caused time- and dose-dependent increases in plasma oxytocin levels under normal conditions. The increase in plasma oxytocin levels in response to i.c.v. choline (150 μg) was greatly attenuated by the pretreatment of rats with atropine (10 μg; i.c.v.), muscarinic receptor antagonist. Mecamylamine (50 μg; i.c.v.), a nicotinic receptor antagonist, failed to suppress the effect of 150 μg choline on oxytocin levels. Pretreatment of rats with 20 μg of hemicholinium-3 (HC-3), a specific inhibitor of choline uptake into nerve terminals, greatly attenuated the increase in plasma oxytocin levels in response to i.c.v. choline injection. Osmotic stimuli induced by either oral administration of 1 ml hypertonic saline (3 M) following 24-h dehydration of rats (type 1) or an i.c.v. injection of hypertonic saline (1 M) (type 2) increased plasma oxytocin levels significantly, but hemorrhage did not alter basal oxytocin concentrations. The i.c.v. injection of choline (50, 150 μg) under these conditions caused an additional and significant increase in plasma oxytocin concentrations beyond that produced by choline in normal conditions. These data show that choline can increase plasma oxytocin concentrations through the stimulation of central cholinergic muscarinic receptors by presynaptic mechanisms and enhance the stimulated oxytocin release.

Potential role for lipoxygenase products of arachidonic acid in prostaglandin F2α-stimulated oxytocin release from the ovine corpus luteum

Intrauterine administration of nordihydroguaiaretic acid (NDGA) will maintain luteal function in sheep and also suppress the release of both oxytocin and prostaglandin F2 alpha (PGF2 alpha) suggesting that 5-lipoxygenase products of arachidonic acid may be involved in ovine luteolysis. During luteolysis, uterine PGF2 alpha is considered to be the major stimulus for the secretion of luteal oxytocin, and we report the effects of 5-lipoxygenase inhibition, via intrauterine NDGA administration, on the ability of PGF2 alpha to effect such secretion. In the NDGA-treated ewes, luteal function was maintained and oestrus delayed, the duration of the oestrous cycle (20 +/- 1 days; mean +/- S.D.; n = 9) being significantly (P < 0.01) longer than in intact controls (15 +/- 1 days, n = 4). Jugular infusions of PGF2 alpha did not stimulate luteal secretion of oxytocin, the effects being comparable with those in ovariectomized ewes. In intact ewes receiving intrauterine infusions of vehicle only, PGF2 alpha produced marked increases in luteal secretion of oxytocin. Also, preinfusion or basal concentrations of oxytocin in this group of ewes (6.6 +/- 1.9 pg/ml) were significantly (P < 0.01) greater than in either the NDGA-treated (3.1 +/- 1.1 pg/ml) or ovariectomized (3.0 +/- 0.6 pg/ml) ewes. The results suggest involvement of 5-lipoxygenase products of arachidonic acid in the release of oxytocin from the ovine corpus luteum.

Oxytocin response to challenging stimuli in elderly men

The present study was carried out in order to establish possible alterations in oxytocin (OT) secretion with aging. Therefore, we evaluated the OT responses to insulin (0.15 U/kg)-induced hypoglycemia or to the administration of angiotensin II (i.v. infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg min; each dose for 20 min) or apomorphine (60 μg/kg s.c.) in male subjects aged 22–80 yr and divided into 3 groups by age (group I ( n=9): 22–38 yr; group II ( n=9): 41–60 yr; group III ( n=9): 63–80 yr). Basal OT concentrations were similar in all groups. The OT response during the insulin tolerance test and the administration of ANG II had similar patterns and magnitudes in all groups. The OT response to apomorphine was similar in the two younger groups, with plasma OT levels increased 118% vs. baseline. In contrast, apomorphine was unable to induce a significant OT rise in the oldest group. During apomorphine test plasma OT concentrations were significantly lower in group III than in groups I and II. For the first time in elderly human subjects, these data show normal responsiveness of the OT secretory system to releasing stimuli such as hypoglycemia and ANG II. These findings indicate that in aged men production of OT and capability of responding to challenging stimuli is unchanged. On the other hand, the reduced OT responsiveness to apomorphine in group III might be an expression of the general dopaminergic dysfunction affecting the aging brain.

Early milk ejection, prolonged parturition and periparturient oxytocin release in the pig

AbstractPlasma oxytocin was measured in 11 multiparous sows for 13 h after the start of parturition to confirm the existence of early milk ejections and determine whether they were associated with pulsatile oxytocin release. The relationship between oxytocin concentrations and duration of parturition was also analysed. Oxytocin was released in pulses during and after parturition and mean concentrations reached maximum 2 to 4 h after the first birth. Discrete milk ejections occurred during parturition but only 42% of these were associated with oxytocin peaks before 4 hpost partum. After this more than 80% of milk ejections occurred with oxytocin peaks. Sow grunting increased during milk ejections and peak grunt rate increased after parturition. Oxytocin peaks without milk ejections did not lead to an increased rate of grunting. Sows with prolonged parturition had lower basal and peak oxytocin concentrations. During the first 4 h only half of the piglets were born during an oxytocin peak. Discrete milk ejections with oxytocin peaks can occur before parturition is completed. However, during the first 4 hpost partum, basal oxytocin concentrations may be high enough for milk ejection to occur without further oxytocin secretion. Both milk ejection and oxytocin release are necessary for the sow to increase grunt rate. Low oxytocin concentration is associated with prolonged parturition.

Release of oxytocin but not corticotrophin-releasing factor-41 into rat hypophysial portal vessel blood can be made opiate dependent

The effects of morphine dependence and abrupt opiate withdrawal on the release of oxytocin and corticotrophin-releasing factor-41 (CRF-41) into hypophysial portal vessel blood in rats anaesthetized with urethane were investigated. Adult female Sprague-Dawley rats were made dependent upon morphine by intracerebroventricular infusion of morphine for 5 days; abrupt opiate withdrawal was induced by injection of the opiate antagonist naloxone. The basal concentrations of oxytocin in portal or peripheral plasma from morphine-dependent rats did not differ significantly from those in control, vehicle-infused rats. In rats in which the pituitary gland was not removed after stalk section, the i.v. injection of naloxone hydrochloride (5 mg/kg) resulted in a large and sustained increase in the concentration of oxytocin in both portal and peripheral plasma in control and morphine-dependent rats. The i.v. injection of naloxone resulted in a threefold increase in the secretion of oxytocin into portal blood in acutely hypophysectomized rats infused with morphine, but did not alter oxytocin secretion in vehicle-infused hypophysectomized rats. The concentration of oxytocin in peripheral plasma in both vehicle- and morphine-infused hypophysectomized rats was at the limit of detection of the assay and was unchanged by the administration of naloxone. There were no significant differences in the secretion of CRF-41 into portal blood in vehicle- or morphine-infused hypophysectomized rats either before or after the administration of naloxone. These data show that, as for oxytocin release from the neurohypophysis into the systemic circulation, the mechanisms which regulate oxytocin release into the portal vessel blood can also be made morphine dependent. The lack of effect of morphine or naloxone on the release of CRF-41 or other stress neuro-hormones suggests that the effect of opiate dependence and withdrawal is selective for oxytocin and is not simply a non-specific response to 'stress'.

Temporal changes in serum prostaglandin F 2α and oxytocin in dairy cows with short luteal phases after the first postpartum ovulation

Luteolysis in the cow depends upon an interaction between prostaglandin F 2α (PGF 2α) and oxytocin. The objectives of our study were 1) to determine oxytocin concentrations in postpartum dairy cows and 2) to identify the temporal relationship between oxytocin and PGF 2α release patterns during luteolysis in normal and abbreviated estrous cycles in the postpartum period. Serum oxytocin and PGF 2α metabolite (PGFM) concentrations from nine cows which had short estrous cycles (< 17 d) were compared with those of six cows which had normal estrous cycles. Serum basal oxytocin concentrations in short estrous cycle cows (23.7 to 31.1 pg/ml) were higher (P<0.05) than those of normal estrous cycle cows (14.6 to 19.8 pg/ml). Oxytocin concentrations increased to peak values in both short and normal cycle cows, during luteolysis. Basal PGFM concentrations (112.2 to 137.4 pg/ml) were higher in cows with short cycle (P<0.05) than in cows with normal cycles (62.9 to 87.5 pg/ml). The increase in PGFM concentrations during luteolysis was significant in both normal cycle and short cycle cows (P<0.05). Increases in serum PGFM concentrations were always associated with increases in serum oxytocin concentrations in normal cycle and short cycle cows and the levels decreased simultaneously before the subsequent estrus. Results support the idea of a positive relationship between PGF 2α and oxytocin concentration during the estrous cycle as well as a possible synergistic action of these hormones in the induction of luteolysis in dairy cattle.

Endocrine changes, with special emphasis on oestradiol-17 beta, prolactin and oxytocin, before and during labour and delivery in goats.

Jugular plasma concentrations of oestradiol-17 beta, prolactin, progesterone and 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured at 2-h intervals during the last 4 days of pregnancy in 6 goats. During advanced labour and delivery, samples were obtained more frequently and assayed for oxytocin. The animals were housed in a barn with continuous dim lighting. A distinct pattern of oscillation in prolactin concentrations, with peaks during the late afternoon, was apparent during the last 3 days. Geometric means of peak concentrations doubled each day and became of longer duration; night-time nadir values remained low except during the last night before parturition. A progressive increase in oestradiol-17 beta, with mean levels doubling every 36 h, was apparent during the last 3 days. There was no sharp pre-partum increase in oestradiol-17 beta. Correlated (r = 0.83) with the increase in oestradiol-17 beta was a gradual increase in PGFM and when the latter reached approximately 1000 pg/ml, the non-reversible decline in progesterone reflecting pre-partum luteolysis occurred. Subsequent changes in PGFM related closely to an approximately 20-fold increase in the ratio of oestradiol-17 beta to progesterone until maximal PGFM levels of 26.5 +/- 4.2 ng/ml were reached at delivery. Basal concentrations of oxytocin (8-15 microU/ml) were measured before the last 60 min and markedly higher, though erratic, concentrations were detected at various times before appearance of the allantochorion. Maximal oxytocin values (range 180-1570 microU/ml) occurred within minutes before or after delivery of the first fetus. The results suggest that increased pre-partum production of oestradiol-17 beta, in addition to provoking sufficient release of prostaglandins to cause luteolysis, may modulate either the sensitivity or set-points for an endogenous rhythm in prolactin secretion at the end of pregnancy. The nature of the oxytocin changes suggest that, after labour has evolved sufficiently, delivery is precipitated by an abrupt increase in oxytocin secretion.

Oxytocin secretion during milking in dairy cows with regard to the variation and importance of a threshold level for milk removal.

Oxytocin secretion in dairy cows was measured during milking by means of a specific radioimmunoassay. Basal oxytocin concentrations before milking recorded from 147 milkings from 21 cows, where an assay method with enhanced sensitivity was employed, were 1.5 +/- 0.6 pmol/l and there was no evidence for any conditioned release of oxytocin. A 1-min manual stimulation before milking evoked a variable but distinct increase in oxytocin concentrations in 188 out of 195 milkings performed using 29 cows. Despite the high variation in absolute concentrations five types of typical secretion pattern could be distinguished. There was no obvious relationship between patterns or absolute concentrations of oxytocin and milk-flow characteristics. Evidence is given that milk ejection seems to follow the threshold principle in that small releases of oxytocin up to a range of 3-5 pmol/l plasma are sufficient to evoke maximum milk ejection.

Half-life, clearance and production rate for oxytocin in cattle during lactation and mammary involution I

Basal concentration, production rate, metabolic clearance rate and T 1 2 for oxytocin were measured in Holstein cows at three lactational stages and during mammary involution. At each lactational stage, oxytocin was given intravenously at .5 IU/min or 1.0 IU/min for 60 min. Infusions were preceded by priming. During involution, the high dose was used. Mean basal concentrations of oxytocin ranged from 8.7 to 21.4 uU/ml. Mean basal values at early, middle, late lactation and involution were 17.57, 12.33, 15.15, 21.13 uU/ml, respectively and differed significantly. The mean “rapid” T 1 2 was 3.87 ± .1 min. Early, middle, late lactation and involution T1 2 s were 4.2, 3.7, 4.0 and 3.5 min, respectively. The rapid T 1 2 was not affected by lactational stage. The mean “slow” T 1 2 was 25.53 ± 1 min. Early lactation and dry period means differed significantly. The overall mean oxytocin clearance rate was 8.41 ± .1 ml/kg ·min. Clearance rate declined through lactation and into the dry period. Mean values of 9.3, 8.8, 7.8 and 7.1 ml/kg ·min were obtained at early, middle, late lactation and involution, respectively. Clearance rates at late lactation and involution differed significantly from one another and from the early and middle stages. Mean entry rates for oxytocin at early, middle, late lactation and involution were 168.79, 106.03, 111.1 and 146.8 uU/kg ·min, respectively. Measurements at early lactation and involution were greater than values for middle and late lactation. To summarize, basal oxytocin concentrations can be measured in cows that are lactating or undergoing mammary involution and changes in concentrations during lactation are related to hormone production (entry rate) and metabolic clearance rates.