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MIRIAM FABIAN
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MARY L. FORSLING
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J. J. JONES
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J. LEE
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SUMMARY

At 4°, the activity of exogenous 8-arginine vasopressin in rat plasma decreased to 50% in 2 days, whereas there was no loss of oxytocin under the same conditions after 3 days. At 37°, oxytocin was not inactivated in 9 hr., whereas 50% of 8-arginine vasopressin was lost in 2 hr.

Forty per cent of exogenous oxytocin in rat plasma was unable to pass through a cellophane (Visking 8/32 in.) membrane, when subjected to a pressure of 100 torr for 18 hr.

In rats under pentobarbitone anaesthesia, progressive haemorrhage of more than 2·0 ml./100 g. induced a secretion of both oxytocin and 8-arginine vasopressin, to produce maximum concentrations of 450 and 700 μ-u./ml., respectively, in the carotid plasma.

In the intact rat (weighing 200–250 g.) anaesthetized with pentobarbitone, 50% of oxytocin in the circulation disappeared within 2 min. after stopping an i.v. infusion of 250–6000 μ-u./100 g./min. The half-time was increased to 4 min. by sham operation, and to 6 or 7 min. by occluding either the renal, or the portal, coeliac and mesenteric vessels. In non-lactating animals, the half-time was 8 min. after clamping both the renal and splanchnic vessels, whereas it was 6 min. in the lactating rat, under the same conditions.

The apparent volume of distribution of oxytocin was 7·3 ml./100 g. in intact rats, and 10–13 ml./100 g. after operation.

The plasma clearance of oxytocin was unaltered in the sham-operated rat, but it decreased after the operative procedures.

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S. J. FOLLEY
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G. S. KNAGGS
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SUMMARY

Oxytocin has been assayed in the jugular vein blood of goats during parturition; for comparison a few measurements were also made during pregnancy. The hormone was extracted from blood plasma by gel filtration, followed by lyophilization and then assayed in the lactating guinea-pig by the increase in intramammary pressure after intra-arterial injection.

No oxytocin could be detected in the blood during pregnancy and it was found in only one of eight goats studied during the first stage of labour. The hormone was present in appreciable quantities in blood taken during the second stage of labour, and in general, the concentration rose to a maximum when the head presented. In cases of twin births oxytocin was usually present in the blood during the birth of the second kid but at a concentration lower than during delivery of the first. After expulsion of the kid the blood oxytocin titre diminished rapidly, suggesting that secretion of oxytocin ceased as soon as the kid was born. In three experiments the total release of oxytocin during a considerable portion (2·7–11·0 min.) of the second stage labour was estimated as 223–726 m-u.

The results are consistent with the view that oxytocin is not essential for the induction of labour. Rather the hormone is released in response to stimuli arising from distension of the vagina and vulva, and by virtue of its contractile effect on the uterus assists parturition.

The half-life of intravenously injected oxytocin in the lactating goat was found to be 1 min. 22 sec. After storage of lyophilized blood extracts at −15° for 5 months milk-ejection activity had declined by only 27%.

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R A D Bathgate
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C Sernia
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Abstract

In this study oxytocin (OT) receptors have been characterized and localized in the testis of the rat using the radioiodinated OT receptor antagonist 125I-labelled d(CH2)5 [Tyr(Me)2,Thr4,Tyr9-NH2]-vasotocin (OTA). Receptor density and localization have been compared with the rat testis arginine vasopressin (AVP) receptor using the radioiodinated AVP V1a receptor antagonist 125I-labelled d(CH2)5Sar7-AVP and the radioiodinated linear AVP V1a antagonist 125I-labelled [(C6H5-CH2CO)-O-methyl-d-Tyr-Phe-Gln-Asn-Arg-Pro-Arg-Tyr-NH2]. 125I-labelled OTA bound with high affinity to membrane fractions of the rat testis (K a = 13·8 ± 1·25 litres/nmol), mammary tissue (K a=20·3± 4·36 litres/nmol) and uterus (K a=27·8±0·74 litres/nmol). Competition studies with various OT and AVP receptor agonists and antagonists confirmed that the binding was to OT receptors. AVP receptors in the testis were found to be identical to AVP V1a receptors in the liver. The AVP receptor density in the testis was much higher than the OT receptor density (109 ±12·3 vs 5·2 ±0·79 (mean ± s.e.m.) fmol/mg protein). Autoradiographical localization showed that both OT and AVP receptors were present in the interstitial spaces in the testis consistent with binding to Leydig cells. AVP receptors were also localized on the epithelial surfaces of the seminiferous tubules and on testicular blood vessels. This study has, for the first time, found OT receptors in the testis of the rat which have similar ligand-binding characteristics to mammary and uterine OT receptors. The receptor localizations are consistent with binding to Leydig cells.

Journal of Endocrinology (1994) 141, 343–352

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A. S. McNEILLY
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H. ALISON DUCKER
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SUMMARY

Blood oxytocin was assayed on the lactating guinea-pig mammary gland. Thirty-six series of serial jugular blood samples were collected from 33 oestrous female goats during normal mating and the transient appearance of oxytocin (2 to 190 μu./ml plasma) was detected in 28 of the series. Coitus did not appear to be a major stimulus for the release of oxytocin. However, oxytocin release occurred in many experiments shortly before coitus when the male was present and continued after coitus for varying times up to 16 min after the male had left the mating room. Oxytocin (9–150 μu./ml plasma) was also released during simulated mating in all six experiments carried out in six dioestrous female goats.

In a further 16 oestrous female goats, oxytocin release (7–73 μu./ml plasma) occurred in response to individual exteroceptive stimuli associated with mating and these stimuli could be classified in descending order of effectiveness in causing oxytocin release as follows: presence of another goat > smell of the male > sound of the male > sight of the male.

The results indicate that oxytocin release occurs in oestrous female goats in response to a complex of stimuli occurring during mating and that physical stimuli associated with coitus are only important in causing oxytocin release during simulated mating in dioestrous female goats.

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S. A. Jones
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A. J. S. Summerlee
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ABSTRACT

The effects of chronic infusion of porcine relaxin on oxytocin release were studied in lactating rats. Infusion of relaxin (4·2 μg/h for either 4 or 6 days) suppressed reflex milk ejection and reduced litter weight gain for 48 h compared with saline-infused controls. After 2 days, neither the rate of growth nor the frequency of milk ejection were significantly different from controls. For 24 h after the infusion of relaxin ended, litters gained weight more quickly than controls but there was no difference seen in the frequency of milk ejection. The effects on oxytocin release of stopping an infusion of relaxin after 3 days were investigated. There was a significant (P <0·01) rise in plasma oxytocin (up to 90 pmol/l) 30 min after the infusion was stopped, followed by a sustained rise in intramammary pressure. Treatment of relaxin-infused rats with naloxone (0·1 mg/kg) when the infusion was halted caused a more rapid release of oxytocin (within 2 min), a greater release of oxytocin (up to 140 pmol/l) and a prolonged rise in intramammary pressure.

J. Endocr. (1987) 114, 241–246

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R. Claus
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D. Schams
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ABSTRACT

Oxytocin concentrations were measured radioimmunologically in sows on the day of standing oestrus over a 6-h period (controls, n=6) or 1 h before and 5 h after mating (n=5) or transcervical infusion of either 100 ml saline (0·9% (w/v) NaCl, n=7) or saline plus 10 μg oestradiol (simulation of seminal oestrogens, n=5).

In the controls, oxytocin was low, at around 1·0 pmol/l, throughout the investigation period. Similarly, saline infusion did not lead to a noticeable change in oxytocin concentrations in six out of seven sows. In one sow, however, infusion led to a maximum of 86 pmol/l at 1 min after infusion. Oestradiol led to no immediate increase in oxytocin concentrations. Later in the post-treatment period (2–5 h) they were only slightly increased (1 pmol/l vs 3 pmol/l). All mated sows reacted with a rapid and clear increase in oxytocin. Maximal concentrations (42·0±5·1 pmol/l; mean ± s.e.m.) appeared 2 min after the onset of ejaculation. Clearly increased concentrations were found for 40 min. It was concluded that mating specifically leads to a rise in oxytocin, probably due to both mechanical and pheromonal stimuli provided by the boar.

Journal of Endocrinology (1990) 126, 361–365

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R. E. J. DYBALL
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SUMMARY

Isolated rat neural lobes were incubated in vitro in Locke's solution containing anaesthetic quantities of urethane, pentobarbitone or tribromoethanol. The oxytocin content of the incubation medium was estimated before, during and after stimulation of the tissue by raising the potassium chloride concentration from 5·6 to 56 mmol/l. Urethane (25 mmol/l) significantly potentiated oxytocin release (P < 0·01) whereas tribromoethanol (0·5 mmol/l) had no obvious effect and pentobarbitone (0·4 mmol/l) significantly (P < 0·01) inhibited its release. Reduction of the sodium chloride concentration in the medium potentiated the release of oxytocin in each case but did not alter its pattern. Urethane which increased secretion of oxytocin also increased calcium ion uptake by the neural lobes and pentobarbitone which decreased oxytocin release decreased calcium ion uptake. The results may explain why the blood concentration of the neurohypophysial hormones tends to be higher in rats anaesthetized with urethane than with tribromoethanol. Inhibition of hormone release by pentobarbitone suggests that this anaesthetic is unsuitable for use in studies of neurohypophysial hormone release. A partial explanation of the anaesthetic properties of urethane and pentobarbitone may also have been found if the release of neurotransmitter substances is influenced in a similar manner.

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J. A. RUSSELL
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D. J. HARRISON
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A. S. McNEILLY
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Two experiments were performed to study the effects of bromocriptine and α-ergocryptine on oxytocin secretion in lactating rats. In both experiments, after overnight separation from their litters, rats were injected with either vehicle alone or ergot alkaloid plus vehicle; 4 h later the litters were returned.

In the first experiment the mothers were conscious. Treatment did not affect suckling behaviour, number of stretch reactions or litter weight gain in the first 30 min. Oxytocin injection before the second 30 min period of suckling caused no extra milk to be obtained. In the second experiment the mothers were anaesthetized with ethyl carbamate (1·1 g/kg body weight) at the time of the ergot alkaloid or vehicle injection. Changes in intramammary pressure were recorded during suckling. Ergot alkaloids altered neither the number of milk ejections caused by suckling, nor the proportion of milk ejections equivalent to 0·2 mu. or more oxytocin.

In both experiments treatment with ergot alkaloids suppressed secretion of prolactin. It is concluded that (a) in suppressing lactation, bromocriptine and α-ergocryptine do not inhibit oxytocin secretion as well as prolactin secretion, and that (b) prolactin secretion is not a necessary concomitant of oxytocin secretion.

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G. K. BENSON
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S. J. FOLLEY
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SUMMARY

The involution of the mammary glands of lactating rats, which normally follows the cessation of suckling, was greatly retarded over a period of 9 days by administering oxytocin to the mothers, following removal of the litters on the 4th day of lactation. This effect was obtained with a commercial extract of the natural hormone, the same extract without preservative (benzethonium chloride), and with synthetic oxytocin. Vasopressin administered under the same conditions had a less well-marked effect. No retardation of mammary involution could be obtained with oxytocin in the absence of the anterior pituitary gland.

Similar results were obtained by administering prolactin to the mothers, but growth hormone (GH) had only a slight effect in maintaining the mammary glands. When both prolactin and GH were given, the maintenance of gland structure was particularly marked.

A majority of the animals receiving synthetic oxytocin showed vaginal mucification which is taken to be indicative of the presence of a luteotrophic hormone (prolactin).

These results are discussed in relation to the possible role of oxytocin in the release of prolactin and other lactogenic and galactopoietic hormones from the anterior lobe.

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R. J. Windle
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M. L. Forsling
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ABSTRACT

Oxytocin concentrations in the plasma, pituitary and hypothalamus of female rats were determined in the morning and evening over the 4-day oestrous cycle. Vasopressin concentrations were also determined to allow calculation of the ratios of the two hormones. The results were compared with those from male rats. Plasma oxytocin concentrations were significantly higher in the evening than in the morning on the day of oestrus. Although the evening concentration achieved was similar on each day of the cycle, morning plasma oxytocin concentrations showed a progressive rise from oestrus to pro-oestrus so that no significant diurnal increases were observed on the other days of the cycle. Vasopressin concentrations in the plasma were also seen to increase over the days of oestrus, dioestrus day 1 and dioestrus day 2. On pro-oestrus the plasma concentrations of vasopressin remained unchanged. The ratio of oxytocin:vasopressin fell during the light hours of the cycle. The hypothalamic content of both hormones showed a rise during the hours of daylight parallel to that seen in the plasma, whereas the pituitary content fell over the same period. The diurnal pattern of hormone release observed in male rats was similar to that in females at oestrus. However, the plasma oxytocin concentrations were significantly higher in the male.

The plasma clearance rate of vasopressin did not vary significantly during the oestrous cycle. However, the plasma clearance rate for oxytocin did show significant variation, being highest on dioestrus day 1 and lowest on dioestrus day 2.

Journal of Endocrinology (1993) 136, 305–311

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