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Regular Article |
a Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, New York 10021
b Institute for Hormone and Fertility Research, University of Hamburg, D-22529 Hamburg, Germany
c Animal Science Department, University of Florida, Gainesville, Florida 32611-0910
d Animal Science Department, Clemson University, South Carolina 29634-0361
ABSTRACT
Plasma oxytocin (OT) concentrations were determined in 14 late-pregnant and parturient Angus-Hereford cows. Jugular and utero-ovarian veins were cannulated for simultaneous withdrawal of blood samples. Samples were collected at 10-min intervals for 6 h once weekly beginning 60–14 days before the date of expected delivery (group 1), or daily 3–7 days before the due date (group 2). In a third group, samples were collected at 15-min intervals every other day for 12 h beginning 1 wk before calving. Basal levels of OT were low, the overall mean for both veins was 0.46 ± 0.03 µU/ml until a week before parturition, and then increased to 0.77 ± 0.1 µU/ml (P < 0.02). Spurts of OT occurred intermittently on all days. Interpeak intervals averaged 71.0 ± 10.7 min until Day -14, and from Day -14 to Day -1 the intervals were 44.0 ± 5.3 min (P < 0.05). From Day -60 to Day -25 the amplitudes of OT peaks were low and similar in both veins (mean 1.37 ± 0.1 µU/ml). From Day -14 to Day -1 the peak amplitudes were 3.6 ± 0.4 µU/ml on average (P < 0.02). During the last 2 wk the utero-ovarian peak of OT was frequently higher than the peripheral peak. In addition, a number of spurts were observed in the utero-ovarian vein only (solo peaks). On the day of parturition during the first stage of labor, peak amplitudes had increased to 7.3 ± 2.0 µU/ml, and the interpeak intervals had become shorter than before labor (mean 25.1 ± 2.6 min). A large surge of OT initiated the expulsive stage of labor. Basal levels rose to 43.1 ± 16 µU/ml and 38.7 ± 12.6 µU/ml, and peak levels to 77.4 ± 19.1 µU/ml and 91.6 ± 21 µU/ml in the jugular and utero-ovarian veins, respectively. Interpeak intervals had decreased to 17.2 ± 3.3 min (P < 0.05). Oxytocin levels remained high after delivery of the calf until the placenta was expelled. The posterior pituitary was the source of circulating OT during most of gestation and labor, but the solo peaks observed during late gestation in the utero-ovarian vein were probably of luteal origin or possibly of caruncular origin, because near term, both tissues express OT mRNA. Fetal posterior pituitary is another possible source for these peaks. Our conclusions are that during bovine pregnancy, low amplitude spurts of OT are secreted intermittently; near term, both the frequency and peak amplitude of the spurts increase; and during labor, a dramatic increase in plasma OT precedes the expulsion of the calf. The main source of OT is the posterior pituitary, but near term, a utero-ovarian source secretes additional OT into the systemic circulation.
corpus luteum, oxytocin, parturition, posterior pituitary, pregnancy
INTRODUCTION
Oxytocin (OT) is the most potent endogenous uterine-stimulating hormone, and OT, or a close analogue of it, is present in all mammals studied thus far. Release of OT during parturition has been demonstrated in humans [1], rhesus monkeys [2], rabbits [3, 4], rats [5, 6], mice [7], some marsupials [8], and cattle [9, 10]. However, there are diverging opinions about the importance of OT in the mechanism of parturition. In a few species, including rabbits [11], rats [12], guinea pigs [13], and the tammar marsupial [14], solid evidence exists that OT has a significant role. In these species, inhibition of OT release or blockade of its action by an antagonist significantly delays the onset of labor, which once started, is grossly prolonged and abnormal. Most of the young are dead when they are finally expelled, one by one with long intervals between, by means of maternal abdominal straining efforts. Evidence also exists in humans for the regulation of uterine contractions by OT during labor. In women with preterm labor, uterine contractions can be stopped by infusion of ethyl alcohol [15], which inhibits OT release [16], or alternatively, by administration of an OT antagonist [17]. In pregnant rhesus monkeys in late pregnancy, administration of an OT antagonist stops the nocturnal, labor-like uterine contractions that normally evolve into labor and delivery [18].
Oxytocin receptors (OTRs) have been found in the myometrium and endometrium of all species studied. In most species uterine OTR concentrations increase markedly at term [19], as shown initially in rats by Soloff et al. [20]. Myometrial sensitivity to OT therefore increases, as demonstrated by Fuchs et al. [21, 22] in rats, and by the classic studies of Caldeyro-Barcia and Theobald [23] in pregnant women, in which normal circulating levels of OT become effective in stimulating uterine contractions at term [1]. These studies support the view that OT plays a physiological role in the process of normal parturition.
In the bovine, endometrial OTR concentrations increase markedly at term, as expected, whereas those of myometrial OTR increase substantially as early as mid-gestation, and thereafter change little before parturition [24]. Circulating OT concentrations would therefore be expected to increase at term, if OT was the factor that elicits the labor contractions in cattle. In the reports published so far [9, 10], plasma levels of OT in parturient cows were found to increase sharply at the time of expulsion of the calf but not before, and the authors concluded that OT action was important in the final stages of parturition only. However, the sampling frequency in these two studies was too low to allow detection of an intermittent mode of OT secretion, as exhibited in parturient women [1], rhesus monkeys [18], and rats [6]. In these species OT is secreted in spurts, the frequency and amplitude of which increase significantly at parturition. Detection of increased secretion rate in such cases requires sampling with short intervals over relatively long periods of time. The present study was conducted to reexamine the characteristics of OT secretion in cows in late pregnancy and parturition. For comparison, plasma OT concentrations were determined in some of the cows during postpartum nursing of their calves. In addition, factors regulating the secretion of OT during these periods are considered.
MATERIALS AND METHODS
Animals
Angus-Hereford cows with known mating dates from the herd of the Animal Science Department at the University of Florida (n = 5) and from the Animal Science Department at the Clemson University, South Carolina (n = 9), were used in this study. Four of the Clemson University cows were cannulated 14–60 days before the expected calving date (group 1) and five were cannulated 3–7 days before the expected date of delivery (group 2). The University of Florida cows were cannulated 1–2 wk before the expected calving date (group 3). A utero-ovarian vein and the left jugular vein or, in one cow, a facial artery, were catheterized under ketamine anesthesia. Blood obtained from the jugular vein at the animal's neck is a mixture of blood that drains both the posterior pituitary and other tissues. The catheters were filled with heparin saline and were taped onto the skin on the back of the animal during the intervals between sampling periods. The Clemson University cows were bled at 10-min intervals from 0700 h to 1300 h approximately once a week beginning 60–25 days before the expected calving date (group 1), or daily during the last week before the expected date (group 2). The University of Florida cows were bled every other day at 15-min intervals from 0600 h to 1800 h beginning 1 wk before the due date. Blood samples were obtained from two of the University of Florida cows on Days 3–4 postpartum during nursing, and after the calves had been separated overnight from the dams. The experiments were approved by the Institutional Animal Care and Use Committees at both universities.
Oxytocin Assay
Oxytocin was extracted from 2 ml of acidified plasma (pH 1.5) by passing the plasma through minicolumns filled with 200 mg of heat-activated Florisil (Sigma Chemical Co., St. Louis, MO) followed by elution with 90% acetone-water [1]. The extracts were air-dried, dissolved in assay buffer, and assayed in duplicate by radioimmunoassay (RIA) as previously described and validated [1]. The highly specific OT antibody was a gift from Dr. Mariana Morris (Department of Physiology, Bowman Gray University Medical School, Winston Salem, NC). The unlabeled OT used as standard was obtained from the National Bureau of Standards, London, United Kingdom. The Bureau uses bioassay to standardize the peptide and the concentration is therefore expressed in international units; 1 IU corresponds to approximately 1.68 µg of peptide. Iodinated OT was prepared by the lactoperoxidase method using OT purchased from Bachem (Torrance, CA), and was purified by column chromatography using Sephadex G-50 columns (Pharmacia, Piscataway, NJ). Bound and free [125I]OT were separated using Pansorbin cells (Calbiochem, San Diego, CA). Extraction recovery was monitored by adding charcoal-treated cow plasma to the standards and extracting them together with the unknowns in each assay; mean recovery was 72.1% ± 3.9%; intraassay and interassay variations were 6.6% and 11.2%, respectively. The least detectable amount was 0.3–0.5 µU per ml. For nondetectable levels the value of the detection limit of the assay was used.
Data Analysis
The RIA results were calculated after logit-log transformation of the data with a computerized program (NIH RIA logit), which also calculates the coefficient of variation at each level of standards and unknowns. The results were analyzed for episodic secretion using the Pulsar Peak algorithm [25] for each individual cow. This program calculates a mean from a floating point window. The cutoff criteria for concentrations above this mean that were defined as pulses were selected as 3 x SD for single peaks, and 2.4 x SD for broader peaks. A calibration data set for the selection of the cutoff criteria was created by analyzing three pools of pregnant cow plasma in 30 duplicate samples each. One pool was charcoal-treated to represent baseline, one had 0.75 µU/ml of OT added to it, and the third had 1.5 µU/ml added to it. This minimized spurious peaks (0% in the baseline pool) and maximized the detection of peaks in the other two pools. The means for the peak concentrations of OT at each pulse and at each blood vessel were calculated for all cows on all days; the means for the basal levels of OT were similarly calculated. The daily means for all cows were obtained from these data in individual cows. All interpeak intervals were also measured for all individual cows on all days, and the daily means for all cows were calculated from the means for the individual cows. Now and then the patency of one of the catheters failed, and when that occurred, samples were obtained from only one blood vessel; sometimes both catheters failed. Comparisons of plasma OT concentrations in the two blood vessels were made on paired samples; the daily means included all samples taken on that day. There was no difference between the OT levels in the samples from the artery and the jugular veins. For convenience, the source of all maternal blood samples is therefore considered to be a vein in the following text. The values given are mean ± SEM, n = number of cows.
Statistical Analysis
The data obtained from samples collected at 15-min intervals during 12 h, and at 10-min intervals during 6 h were analyzed using the Pulsar program as described above. The means for the peak amplitudes for the identified pulses and the interpulse intervals were calculated for each day for each cow as described above. Differences in the daily peak amplitudes and interpeak intervals among cows were analyzed by least squares multiple regression using the general linear models procedure [26]. The OT peaks were divided into the following categories according to the relative amplitudes in the two veins: 1) amplitude highest in peripheral vein plasma, 2) amplitude highest in utero-ovarian vein plasma, 3) peak amplitudes were equal in plasma from both veins. The distribution of daily peaks in these categories was submitted to chi-square analysis to determine whether or not it was random. Peaks that were not coincident in the two veins were considered solo peaks when the amplitude of this peak was equal to or greater than 3 x SD for the mean difference in the OT concentrations between all coincident samples on that particular day. P < 0.05 was considered significant.
RESULTS
Plasma Oxytocin Concentrations
Plasma OT concentrations in both veins were low until about 2 wk before term. Concentrations of OT remained at basal levels for long periods of time with spurts of OT occurring simultaneously in the peripheral and the utero-ovarian vein blood with about hourly intervals. The amplitudes of these intermittent peaks varied depending on the stage of gestation as did the interpeak intervals. The peak OT concentrations and interpeak intervals were relatively uniform until near term when the amplitudes had increased and intervals had decreased.
Basal concentrations Basal concentrations of OT were similar in peripheral and utero-ovarian vein plasma. Between Days -60 and -14 the mean concentrations in the plasma of the two veins were 0.44 ± 0.017 µU/ml and 0.47 ± 0.064 µU/ml, respectively. Between Days -14 and -1 the basal concentration of OT in peripheral plasma was 0.71 ± 0.161 µU/ml (not significant NS vs. before), and 0.82 ± 0.086 µU/ml in utero-ovarian vein plasma (P < 0.02 vs. before). On the day labor began (Day 0) the basal levels had increased significantly in both veins and were 1.56 ± 0.41 µU/ml (P < 0.02 vs. Days -60 to -14) in the peripheral vein and 1.34 ± 0.05 µU/ml (P < 0.001 vs. all days) in the utero-ovarian vein.
Interpeak intervals In general, the concentrations of plasma OT changed in a parallel manner in both vessels, but occasionally, the concentration of OT in only one of the two blood vessels, usually the peripheral vein, satisfied the criteria for a pulse. As a result, the means for the number of peaks per day and for the duration of interpeak intervals in the two vessels were not always the same. From Day -60 to Day -14 the mean interpeak interval was 61 ± 1.6 min in peripheral vein plasma and 93 ± 13 min in utero-ovarian vein plasma (P < 0.02). During the last 14 days before parturition the means were 42.0 ± 8.4 min and 58.6 ± 20 min, respectively (NS). In the morning of the day labor began the interpeak intervals had decreased significantly from earlier values in both vessels (P < 001); the means were 32.1 ± 5.0 min in peripheral vein plasma and 38.5 ± 8.4 min in utero-ovarian vein plasma.
Duration of OT peaks The duration of the peaks could not be determined from the available data, but in all instances it was less than the sampling intervals.
Peak concentrations of OT During the period between Days -60 and -14 the peak concentrations of OT were relatively constant and similar in all cows studied. OT levels in both peripheral plasma and utero-ovarian vein plasma were also similar, the mean for both was 1.4 ± 0.1 µU/ml. The character of OT secretion was also similar on all days, consisting of low-amplitude spurts appearing in clusters or as singletons (Fig. 1). No significant differences between the peak amplitudes in the peripheral and utero-ovarian veins were observed.
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During the period from Day -14 to Day -1 the concentrations of OT peaks had increased significantly from the earlier stage (P < 0.005). The mean pulse amplitude was 3.0 ± 0.1 µU/ml in jugular vein plasma and 3.7 ± 0.6 µU/ml in utero-ovarian vein plasma (NS). The concentrations of OT were also more variable than they were earlier in gestation; the daily means varied from 2.4 ± 0.8 µU/ml on Day -14 to 6.4 ± 4.4 µU/ml on Day -1 (NS). An example is shown in Figure 2.
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Labor and delivery The transition from no labor to labor was gradual, and the beginning of labor was often difficult to ascertain with certainty. Behavioral changes such as restlessness were the first outward signs of labor. The cows did not eat much, they frequently changed position, and repeatedly laid down and got up. In several cows, bulging membranes were visible through the vulva, indicating that the cervix had softened. Most cows delivered their calves in late evening or at night. In two of the cows sampled from 60 days before delivery date, the fetuses had been aborted at about 260 days of gestation, and three other cows delivered unobserved before the due date. On a cold night, one cow was left alone overnight after having been in labor for 9 h without progress; the next morning a dead calf was found with the cow. Plasma samples during labor and delivery were obtained from eight cows, although samples were not always obtained from both catheters at the same time. Problems with the patency of the catheters were encountered more frequently during labor and delivery than earlier in gestation, perhaps because of the characteristic restlessness observed in all parturient cows. In three cows samples were obtained from only one vessel; the utero-ovarian vein in one cow and the jugular vein in two cows. In a fourth cow samples were obtained sometimes from the jugular vein and other times from the utero-ovarian vein. Simultaneous samples from both veins were obtained from four cows, although usually with some interruptions.
The duration of the first stage was 5.8 ± 1.8 h measured from the time the frequency of the OT pulses increased until the time the cow started to strain and push. The duration of the second stage from this time until the expulsion of the calf was 85 ± 20 min.
During the first stage of labor OT secretion continued in an episodic manner. The interpeak intervals were shorter and the peak amplitudes were greater than before the onset of labor; in some cows they were similar in the two veins, and in others the peak amplitudes were greatest in the utero-ovarian vein plasma. The mean peak amplitude was 7.2 ± 1.9 µU/ml. The interpeak intervals were 25 ± 7.8 min in utero-ovarian vein plasma and 26.7 ± 6.5 min in peripheral vein plasma.
The second stage of labor was associated in all but one cow with a large surge of OT into the circulation, during which the calves were expelled. Basal levels rose abruptly to a mean of 43.1 ± 16 µU/ml in peripheral vein plasma and 34.3 ± 11 µU/ml in utero-ovarian vein plasma. Peak concentrations during the surge reached up to 225 µU/ml and averaged 77.4 ± 19 µU/ml in the peripheral vein and 91.6 ± 21 µU/ml in the utero-ovarian vein (NS). The mean interpeak intervals were 16.7 ± 3.2 min and 17.7 ± 3.9 min, respectively. Calves were delivered within 1–2 h. The surge of OT continued at a somewhat lower level than before the delivery of the calf until the placenta was expelled, from 20 min to 3.4 h after the calf had been delivered. During this, the third stage of labor, the mean concentration of plasma OT was 28 ± 12.5 µU/ml. An example of plasma OT levels during labor and delivery is shown in Figure 3.
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The duration of labor until the delivery of the calf varied considerably among cows, from 4 to 14.5 h; the differences were mainly due to variations in the length of the first stage of labor. The surge of OT appeared to be elicited by pressure of the head against the cervix as suggested by the findings in one cow with an unusually large fetal head that remained in the pelvis during more than 12 h of labor. Spurts of OT were secreted with great frequency but no surge of OT was elicited spontaneously nor during vaginal and cervical palpation and installation of head pullers. A surge of OT was promptly initiated when the head was pulled from the pelvis into the cervix.
Figure 4 shows plasma OT levels in a cow in which both catheters remained patent during labor. Numerous peaks of OT in utero-ovarian vein plasma were greater than those in peripheral vein plasma both before and during labor. In this cow, considerable amounts of OT from a utero-ovarian source were apparently secreted into the peripheral circulation.
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The results for all experimental cows are summarized in Table 1.
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Comparison of utero-ovarian vein and peripheral plasma OT concentrations Until Day -25 peak concentrations of OT were higher in peripheral vein plasma than in utero-ovarian plasma, or they were equal in the two veins (categories 1 and 3). From Day -14 onward, category 2 spurts (peak amplitudes greater in the utero-ovarian vein than in the peripheral vein) were observed now and then, and became more frequent as parturition approached. On Days -5, -3, -1, and 0 the four cows in which both catheters were in working order had more category 2 peaks than category 1 peaks (P < 0.02). Overall, 12.5% of all coincidental OT spurts belonged to category 2. In addition, during the last days of pregnancy several peaks of OT were observed only in utero-ovarian vein plasma and were not accompanied by a peak in peripheral vein plasma. An example is shown in Figure 5. During the surge of OT the jugular vein concentrations were always greater than or equal to the utero-ovarian vein OT concentrations.
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OT release at nursing On Days 2 and 5 postpartum the calves of two cows were separated from their mothers overnight. The next day blood samples were collected from the jugular vein of the two cows at 5-min intervals for 15 min before and 60 min after the calves had been returned. Basal and suckling-induced OT levels varied considerably in both cows. During nursing the secretion of OT was intermittent (Fig. 6). A major spurt occurred within 5 min after suckling began, with mean peak OT concentrations reaching 6.9 ± 1.0 µU/ml. The peak plasma OT levels declined while the calf was still nursing, but smaller spurts between 2 and 3.5 µU/ml occurred in 10- to 15-min intervals after the calf had stopped nursing until the experiment was terminated.
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DISCUSSION
Our results indicate that in pregnant cows OT is secreted intermittently during the last 2 mo of pregnancy and during the first stage of labor. A large surge of OT was secreted during the second stage of labor, when a rapid expulsion of the calf is essential for its survival, but at nursing, postpartum OT secretion was again intermittent. OT administered intermittently has been shown to be more efficacious than continuously administered OT in terms of the amount of the peptide needed for induction of labor and delivery both in humans [27] and in rats [28]. Moreover, the myometrial effects of OT were shown to be enhanced in response to intermittent administration in comparison to the effects of continuous infusion [28].
The increases in OT secretion during late pregnancy coincided temporally with major changes in the concentrations of circulating estrogens and progesterone in cows [29, 30]. The first significant increase in OT secretion occurred about 2 wk before the onset of labor. At this time, plasma estrogen levels rise and concentrations of progesterone begin to decline. At the time of the second increase in OT secretion, shortly before the onset of labor, plasma progesterone concentrations fall steeply to nonpregnant levels and the rate of estradiol secretion increases rapidly. These observations suggest that ovarian steroids participate in the regulation of OT secretion in cows. Further support for this view is provided by the finding that estrogen increases production of OT in the hypothalamic magnocellular nuclei and facilitates the release of OT from the posterior pituitary lobe [31]. In addition, increasing estradiol concentrations and withdrawal of progesterone have been shown to increase the frequency of OT pulses secreted from the posterior pituitary in sheep [32]. The authors suggested the existence of a putative, central OT pulse generator, the activity of which is regulated by ovarian steroids [32]. This hypothesis is in agreement with the present findings in cows.
The largest increase in OT secretion was seen during late labor, when no significant changes are known to occur in ovarian steroid levels. The surge of OT probably occurred in response to a neural reflex elicited by pressure of the fetal head against the lower segment of the uterus and the cervix. Using rabbits as experimental animals, in 1941, Ferguson postulated that distension of the vagina caused a release of OT from the neurohypophysis. This was supported by experiments in nonpregnant sheep and cows [33, 34]. However, in parturient cows, manual palpation of the vagina did not result in a surge of OT, as explained above. The head of the calf of this cow remained in the pelvis and did not exert pressure against the cervix until the head was forcibly pulled into the cervix, and this was immediately associated with a surge of OT.
Endogenous opioids may also be involved in the regulation of OT release at the onset of labor. The oxytocin cells in the brain and the noradrenergic inputs to oxytocin neurons have been found to be extremely sensitive to inhibition by endogenous and exogenous opioid peptides [35, 36]. Withdrawal of endogenous opioid inhibition may therefore be necessary for neural stimuli from the reproductive tract to reach the oxytocin cells in the brain. The characteristic state of restlessness shortly before and at the onset of labor that was common for all experimental cows may have resulted from a withdrawal of endogenous opioids. Similar behavioral changes precede the onset of labor in other species studied [11, 21].
The majority of OT spurts originated in the neurohypophysis, judging from the fact that jugular vein plasma concentrations of OT were higher or equal to those in the utero-ovarian vein in all coincident peaks before Day -14. During the last 14 days an increasing number of coincident peaks had higher OT concentration in utero-ovarian vein plasma than in jugular vein plasma. In addition, close-to-term peaks of OT were observed in the utero-ovarian vein that were not associated with concomitant peaks in the peripheral vein. Most likely these solo peaks originated from a utero-ovarian source, probably the corpus luteum. This finding was unexpected because the expression of OT mRNA and the synthesis of the OT peptide in the corpus luteum ceases around Day 50 of pregnancy. Recently, however, the corpus luteum of pregnant cows was found to have resumed the expression of OT mRNA near term [37]. Maternal caruncles are another putative source of OT in the utero-ovarian vein because caruncles, too, were found to express increasing amounts of OT mRNA near term [37]. The fetal pituitary might also be a source of OT secreted into the maternal utero-ovarian vein, as shown in humans and baboons [38–40]. By contrast, in pregnant rhesus monkeys, exogenous oxytocin injected into the fetus did not appear to cross the placenta into the maternal circulation [2], whereas in the ewe, oxytocin can cross the placenta from maternal to fetal circulation [41], and indirect evidence suggests that OT also crosses in the opposite direction [42].
In conclusion, during bovine pregnancy, OT is secreted intermittently. The amplitude and frequency of the OT spurts remain low until about 2 wk before parturition. The rate of secretion then increases step-wise rather than gradually. The first and second increases coincide with major changes in the secretion of ovarian steroids, suggesting that these hormones may regulate the secretion of OT. The third step was not associated with any changes in steroid levels and was probably caused by a neural reflex arising from the pressure of the fetal head against the cervix. A substantial increase in OT secretion 2 wk before the onset of labor suggests that OT also participates in the preparation of the reproductive tract for parturition, in addition to its excitatory effects on uterine contractions during labor. The posterior pituitary is the major source of circulating OT during parturition, but a minor part of the total OT derives from a utero-ovarian source, the corpus luteum being the most likely source of this OT.
ACKNOWLEDGMENTS
The authors acknowledge the gift of the OT antibody by Dr. Mariana Morris, Department of Physiology, Bowman Gray University Medical School, Winston Salem, North Carolina; and the excellent assistance of Dulce Navarro, B.S., in the performance of the oxytocin assays.
FOOTNOTES
First decision: 22 February 2000.
1 Supported in part by the Florida Agricultural Experiment Station and a grant from Warner Lambert Foundation (A-R. F.) and approved for publication as Journal Series R-08181. 
2 Correspondence: Anna-Riitta Fuchs, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, 515 East 71st Street, S-515, New York, NY 10021. FAX: 212 860 1134; annariitta{at}aol.com
Accepted: May 11, 2001.
Received: January 18, 2000.
REFERENCES
and E2 release. In: Ivell R, Russel JA (eds.), Oxytocin. Cellular and Molecular Approaches in Medicine and Research Adv Exp Med Biol 1995; 395:405-420[Medline] in maternal plasma of the pregnant cow in relations to the initiation of parturition. J Reprod Fertil 1974; 36:1-8[Medline]This article has been cited by other articles:
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|
 |
|
  G. Hirsbrunner, P. Zanolari, H. Althaus, J. Husler, and A. Steiner Influence of prostaglandin E2 on parturition in cattle Vet Rec., September 22, 2007; 161(12): 414 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Suzuki, K. Shibata, F. Kikkawa, H. Kajiyama, K. Ino, S. Nomura, M. Tsujimoto, and S. Mizutani Possible Role of Placental Leucine Aminopeptidase in the Antiproliferative Effect of Oxytocin in Human Endometrial Adenocarcinoma Clin. Cancer Res., April 1, 2003; 9(4): 1528 - 1534. [Abstract] [Full Text] [PDF]
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|
|
 |
|
 R. Telgmann, R. A.D. Bathgate, S. Jaeger, G. Tillmann, and R. Ivell Transcriptional Regulation of the Bovine Oxytocin Receptor Gene Biol Reprod, March 1, 2003; 68(3): 1015 - 1026. [Abstract] [Full Text] [PDF]
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