Higher Oxytocin Concentrations Research Articles

Ovarian secretion of oxytocin is stimulated by prostaglandin.

Oxytocin induces regression of corpora lutea when administered to several domestic species1–3 and a role for endogenous oxytocin in controlling the ovarian cycle is supported by the delay in luteal regression observed in sheep which have been immunized against oxytocin4. Although the posterior pituitary is the major source of oxytocin released at parturition and before suckling, recent evidence suggests that during the oestrous cycle the ovary may also secrete oxytocin. Circulating oxytocin and progesterone levels change in parallel during the oestrous cycle and after ovariectomy5–7, and the corpus luteum8 (but not other ovarian tissues [A.P.F.F. and E.L.S., unpublished]) contains high concentrations of oxytocin. We now extend this evidence by showing that in sheep, the concentration of oxytocin in ovarian venous blood exceeds that in arterial blood, and we find that ovarian secretion of oxytocin is stimulated by a prostaglandin F2α analogue.

Oxytocin release and uterine activation during parturition iin rabbits.

Plasma oxytocin was measured by a specific RIA in blood of pregnant and parturient rabbits obtained through an indwelling cardiac catheter. Uterine activity was continuously recorded by means of indwelling intrauterine balloons. Plasma oxytocin concentrations were low throughout gestation (mean +/- SE, 16.1 +/- 2.0 pg/ml), with no rise toward term. During parturition, a significant increase in plasma oxytocin was observed in all but 3 of 21 rabbits studied. Plasma oxytocin rose rapidly and reached high levels within minutes of the beginning of labor contractions. The mean concentration was 193 +/- 55 pg/ml (SE) 30--60 sec before the expulsive phase. The highest oxytocin concentrations were usually observed at the delivery of the first fetus (mean, 258 +/- 89 pg/ml); this was followed by a rapid decline. Baseline levels were reached in 20--60 min. Uterine activity during parturition was well correlated with plasma oxytocin; an abrupt increase was observed a few minutes (5.1 +/- 1.2 min) before the expulsion of the young, followed by a gradual disappearance over 30--70 min. Little or no circulating oxytocin was detected during delivery in 3 rabbits. In these, the course of parturition was abnormal and protracted, resulting in a high percentage of stillborn young. The series of strong contractions associated with normal delivery was absent. By contrast, abortion in 2 rabbits was associated with elevated plasma oxytocin levels and increased uterine activity. These findings indicate that a substantial amount of oxytocin is released into the circulation during delivery and suggest that the normal activation of the uterus at parturition depends on oxytocin. The stimulus eliciting the release of oxytocin is not known. Dilatation of the birth canal by the passage of a fetus was not consistently followed by detectable oxytocin release, and during delivery, a second release of oxytocin was often unrelated to any apparent stimulus. Intact spinal cord caudal to T5 does not appear to be essential for the release of oxytocin at parturition, since spinal transsection in 2 rabbits was associated with normal oxytocin release at delivery. Injections of synthetic oxytocin caused a dose-dependent increase in plasma oxytocin and uterine activity. Disappearance of oxytocin from the circulation followed a double exponential curve; the mean half-life of the initial rapid phase was 1.82 min after single injections and the half-life of the low component was 26.5 min. The initial volume of distribution was close to the volume of the vascular compartment, and the total apparent volume of distribution was about twice the size of the extracellular compartment. After constant infusions, a half-life of 3.6 min was obtained for the uncorrected values during the initial phase.

Studies of oxytocin in the baboon during pregnancy and delivery.

Oxytocin was determined by radioimmunoassay in pregnant baboons throughout gestation, in the foetus at caesarean section, and after oxytocin infusion into the mother and foetus. Serial maternal plasma oxytocin in 6 baboons during pregnancy showed a significant correlation between the gestational age and maternal plasma oxytocin concentrations with a correlation coefficient of r = 0.3185 and P less than 0.005. Seventy-one out of 75 plasma samples (94.7%) during pregnancy had detectable levels of oxytocin. Uterine vein plasma had higher oxytocin concentrations than maternal plasma and amniotic fluid (18.6 +/- 4.6 pg/ml; mean +/0 SE) but lower than umbilical, jugular vein and cardiac blood from the foetus. Foetal pituitary gland contained 5.4--26.1 micrograms oxytocin/g. Regular uterine contractions were established with iv oxytocin of 4--20 mU/min and the plasma oxytocin measured showed a significant correlation with the uterine activity achieved (r = 0.64, P less than 0.001). The disappearance of plasma oxytocin at 179 days gestation gave an apparent half-life of 1.1 and 1.7 min in 2 baboons with a late half-life of 9.9 and 17.3 min, respectively. In one baboon at 171 days gestation, the apparent half-life of oxytocin was 9.9 min. The metabolic clearance rates were calculated to be 3.1, 3.2 and 11.7 ml/kg/min, respectively. The production rates were 97, 74, 390 pg/kg/min, respectively. Oxytocin injected into the umbilical vessel near term showed an increase in oxytocin concentration in maternal and uterine vein plasma and amniotic fluid, suggesting that oxytocin can cross the placenta from the foetal to the maternal side. Our findings indicate that in the baboon (1) oxytocin is present throughout pregnancy, (2) uterine activity can be correlated with plasma oxytocin during oxytocin infusion, (3) foetal circulation has higher oxytocin concentration than maternal blood and (4) oxytocin probably can cross the placenta from the foetus to the mother.

In Vitro Analysis of the Participation of Oxytocin and Vasopressin in the Gonadotropin Releasing Hormone-Induced Release of LH

SummaryThe pituitary perfusion technique was used to investigate the possible interaction between the neurohypophyseal hormones and gonadotropin releasing hormone (GnRH). The perifusion of rat anterior pituitaries with 0.2 mU/ml arginine vasopressin (AVP) resulted in a significant (P < 0.05) increase in LH release over baseline, while higher doses had no effect. When combined with GnRH, this and higher concentrations of AVP did not alter the GnRH-induced release of LH. Three concentrations of oxytocin (OT): 0.02, 0.2 and 20 mU/ml, increased baseline secretion of LH (P < 0.05) while 2 mU/ml OT did not. When added to GnRH-containing perifusion media, 0.02 mU/ml OT caused significant (P < 0.05) enhancement and prolongation of the LH response to GnRH. All higher concentrations of OT and one concentration that was tenfold lower, did not exhibit potentiating effects. When the pituitary tissue was pretreated with AVP or OT prior to stimulation with GnRH, only the same concentration of OT (0.02 mU/ml) was effecti...

A sensitive and specific assay for vasopressin in the circulating blood.

1. A search was made for an assay tissue with selective sensitivity to vasopressin. Of those smooth muscle preparations tested, the longitudinal muscle of the isolated rectum of the rabbit was the most satisfactory.2. The rabbit isolated rectum, bathed in Krebs solution, was contracted by acetylcholine, angiotensin II amide, bradykinin and 5-hydroxytryptamine. It was relaxed by vasopressin, oxytocin and the catecholamines.3. Vasopressin was active in concentrations of 4-100 muu./ml (0.01-0.25 ng/ml) and was 20-30 times more active than oxytocin. Bretylium had no effect on the relaxant action of vasopressin; nor did concentrations of alpha- and beta-adrenoceptor blocking agents sufficient to abolish the actions of catecholamines. Lignocaine reduced the sensitivity of the rabbit rectum to both vasopressin and oxytocin without altering the actions of adrenaline. High concentrations of either vasopressin or oxytocin desensitized the rabbit rectum to the actions of both hormones, without affecting the actions of adrenaline. It was concluded that vasopressin and oxytocin act on a common population of receptors different from those for catecholamines.4. Phentolamine, unlike other alpha-adrenoceptor antagonists, reduced the relaxant action of vasopressin on the rectum.5. When superfused with blood from an anaesthetized dog, the rabbit rectum maintained a higher tone than in Krebs solution; it retained its sensitivity to vasopressin. Pronethalol, administered intraluminally, reduced spontaneous movement and abolished the actions of low concentrations of catecholamines, thereby increasing the specificity of the assay. No other substance tested relaxed the rectum in concentrations likely to be found in blood.6. Vasopressin was stable in dog's blood; it survived passage through the pulmonary vascular bed; it had a half-life in the circulation of about 1 min.7. The half-life of vasopressin in the circulation may depend upon the duration of the infusion.

TRANSFER OF OXYTOCIN FROM THE MATERNAL TO THE FOETAL CIRCULATION IN THE EWE.

LITTLE is known of the transfer of peptides between the maternal and fœtal circulation. In their exhaustive review, Hagermann and Villee1 mention the results of the work of Krzysztoporski2, who showed that simple peptides cross the placental barrier, and those of Knobil and Josimovitch3 that insulin crosses the mono-layered placenta of the rat. Other information on the placental penetration of peptide hormones is sparse and contradictory. High concentrations of oxytocin in maternal blood during parturition have been reported4 and it seemed therefore of interest to investigate the possibility that oxytocin in the maternal circulation might reach the fœtus.

Missed abortion

Sixty-six cases of missed abortion treated at the Mayo Clinic in the period January 1958, through June 1962, have been reviewed. Experience with high concentrations of oxytocin (Pitocin) in the medical management of these cases was limited, and determination of the value of this technique for active induction awaits further experience. A trend in this series toward more active management of missed abortions has been demonstrated with 62 per cent of 66 cases being managed surgically. Specific preparations for clotting deficiencies are urged in all cases of missed abortion.