Progesterone withdrawal induced by ICI 81008 in pregnant rats

Of a total of 343 pregnant rats treated with the prostaglandin F2 analogue ICI 81008, 137 aborted, while 83 had reduced and 123 intact litter. These biological variations depended primarily on the gestational timing of treatment and on the dose and route of administration of this synthetic PG. In comparison with the 107 controls, all experimental rats which aborted had a drastic reduction in plasma progesterone levels which was highly significant (P<0.001) until day 18. In contrast, those animals which escaped suboptimal ICI 81008 treatment with a partly resorbed litter, only had a moderate reduction in progesterone which was statistically significant (P<0.01) until day 16 when the levels of this steroid normally begin to decrease. Ineffective treatment did not affect progesterone levels and intact pregnancy. In contrast to progesterone, there was no correlation between plasma estradiol-17β levels and the consequences of ICI 81008 treatment.

ICI 81008 was most effective between the 6th and 12th days of gestation, when plasma progesterone in the normal controls showed a nadir. Effective treatment reduced plasma progesterone within 6 hours. Evidently the pharmacologically provoked endocrine imbalance precedes the cessation of characteristic gestational weight gain, uterine bleeding and abortion which only manifest 24 to 48 hours after treatment.     

Pregnancy termination in the rat “model” by a synthetic prostaglandin analogue ICI 81008

The abortifacient efficacy of the PGF2α analogue ICI 81008 had been examined in 378 Spraque-Dawley rats. Of the 3 systemic routes of administration studied: intramuscular (i.m.), subcutaneous (s.c.) and per vaginam (p.v.), the p.v. treatment had been the most effective. Complete abortions were provoked invariably by a single p.v. dose of 20 μg ICI 81008 in the broad gestational range of 6 to 10 days of pregnancy and the “abortion rate” (AbR) remained 86% at day 12. The reduction of the p.v. dose to 10 μg only decreased efficacy slightly and its increase to 40 μg improved it. The analogue ICI 81008 was highly more effective than the natural PGs: F2α and E₂, in spite of their comparable oxytocic actions on the excised uterus. This high efficacy of ICI 81008 in p.v. formulation, without apparent side effects, is a therapeutic promise which demands early clinical investigation.At day 3 the AbR decreased to 0% and at day 14 to 30%. Plotting AbR, as a function of the gestational timing of treatment, yielded a reversed U shape curve, which reflected upon the mechanism of ICI 81008 action. The pituitary, the corpus luteum and the blastocyst are equally indispensable and accessible to drugs at days 3 and 6 of gestation. Yet the efficacy of ICI 81008 increased from 0% to 100% during this 3 days period, suggesting that the primary target of ICI 81008 is the uterine environment of the implanted conceptus. Thus the earlier premise had been substantiated that in inducing abortion PGs provoke: reduction of uterine microcirculation, sustained contracture, suppression of feto-placental endocrine function (including luteotrophic support), luteolysis, progesterone (P)-withdrawal and the evolution of uterine activity.However, progesterone treatment prevented the effect of ICI 81008, completely or partly, depending on the dose of PG administered. Furthermore, extensive studies of the ICI research team showed that ICI 81008 can provoke luteolysis without pregnancy, suggesting that under certain conditions the ovary is the primary target of this drug. If this effect on the ovary also involves a microcirculatory disturbance, then the mechanism of action of ICI 81008 is retained, in a variety of species and reproductive conditions, and only the threshold of the organ serving as primary target changes.From the Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MissouriThis work was supported by the Agency for International Development Contract AID/csd 3160 and the National Institute of Health Career Award, HD 20169-11.     

Luteolysis induced in pigtail monkeys (Macaca nemestrina) with prostaglandin f 2 alpha, ICI 80996 and ICI 81008.

Non-pregnant pigtail monkeys (M. nemestrina) were given ICI 80996 subcutaneously and ICI 81008 and PGF2alpha subcutaneously or intravaginally, once daily on days 20-30 inclusive, or two or three times on days 24 or 26 only. Doses of 50 mug/kg of ICI 80996, 100 mug/kg of ICI 81008 and approx. 1 mg/kg of PGF2alpha were used. In the majority of monkeys treated subcutaneously a rapid fall in circulating progesterone concentrations and earlier than normal menstrual bleeding occurred. When given per vaginam, ICI 81008 was as effective as when given subcutaneously, though PGF2alpha was less effective intravaginally than by the subcutaneous route.     

Menstrual induction with the PGF2alpha-analogue ICI 81008.

"Menstrual Induction" (MI) has been studied in 79 volunteers, using the therapeutic principle of "PG-Impact". The PGF2alpha analogue: ICI 81008 was administered under strictly aseptic precautions into the uterine cavity during the 4th week of pregnancy. The treatment catheter (inserted through the cervical canal) delivered a single dose of only 100-200 mug ICI 81008 during the pilot study with this new drug. When it was established that the side effects were acceptable, this moderately effective dose was increased at first to 200-300 mug and eventually to 400 mug. At the 400 mug dose level, 29 (76%) of the 38 study patients had complete and 8 (21%) incomplete abortions, while 1 (3%) failed to bleed. Those 9 women who had incomplete abortions or failed to abort were curetted. In comparison with PGF2alpha (428 cases) and PGE2 (114 cases), ICI 81008 (38 cases at the 400 mug level) provoked lesser side effects, excepting the transient increase in blood pressure. All patients (whose intrauterine pressure was measured) responded to the ICI 81008-impact with rapidly developing high level uterine contracture. Plasma progesterone decreased significantly if treatment was successful and insignificantly in cases of treatment failure. In current studies, the efficacy of the vaginal delivery system of ICI 81008 is examined.     

Menstrual induction with the PGF2α-analogue ICI 81008

“Menstrual Induction” (MI) has been studied in 79 volunteers, using the therapeutic principle of “PG-Impact”. The PGF2α analogue: ICI 81008 was administered under strictly aseptic precautions into the uterine cavity during the 4th week of pregnancy. The treatment catheter (inserted through the cervical canal) delivered a single dose of only 100–200 μg ICI 81008 during the pilot study with this new drug. When it was established that the side effects were acceptable, this moderately effective dose was increased at first to 200–300 μg and eventually to 400 μg.At the 400 μg dose level, 29 (76%) of the 38 study patients had complete and 8 (21%) incomplete abortions, while 1 (3%) failed to bleed. Those 9 women who had incomplete abortions or failed to abort were curetted. In comparison with PGF2α (428 cases) and PGE₂ (114 cases), ICI 81008 (38 cases at the 400 μg level) provoked lesser side effects, excepting the transient increase in blood pressure.All patients (whose intrauterine pressure was measured) responded to the ICI 81008-impact with rapidly developing high level uterine contracture. Plasma progesterone decreased significantly if treatment was successful and insignificantly in cases of treatment failure. In current studies, the efficacy of the vaginal delivery system of ICI 81008 is examined.     

Progesterone administration prolongs the inhibitory effects of hyperprolactinemia on luteinizing hormone secretion in acutely ovariectomized rats

Several studies have shown that hyperprolactinemia in rats inhibits the post-gonadectomy rise in plasma luteinizing hormone (LH) for a limited period only. In intact rats the suppression of plasma LH during hyperprolactinemia is more prolonged. In the present study we have examined the possibility that the elevated levels of progesterone brought about by the raised plasma prolactin levels in intact rats are involved in the maintenance of LH inhibition. We have observed the effect of exogenous progesterone administration during the early post-ovariectomy period on plasma LH levels in female rats made hyperprolactinemic by administration of the dopamine antagonist, domperidone. Following ovariectomy of virgin, female rats, plasma LH was determined on each day from Day 3 to Day 10 after ovariectomy. In control rats plasma LH had increased by approximately 5-fold during the period of the experiment. In control rats treated with progesterone the rise in plasma LH was inhibited temporarily but LH had increased to similar levels to the controls by Day 10. In hyperprolactinemic rats LH was suppressed until Day 7, after which significant rises were observed. However, in hyperprolactinemic rats treated with progesterone, LH did not rise in a similar fashion, and remained low throughout the experiment. We conclude that a combination of hyperprolactinemia and raised plasma progesterone concentrations is necessary for the continued inhibition of LH release after ovariectomy.     

Luteolysis induced in pigtail monkeys (Macaca nemestrina) with prostaglandin F2α, ICI 80996 and ICI 81008

Non-pregnant pigtail monkeys (M. nemestrina) were given ICI 80996 subcutaneously and ICI 81008 and PGF_2α subcutaneously or intravaginally, once daily on days 20–30 inclusive, or two or three times on days 24 or 26 only. Doses of 50 μg/kg of ICI 80996, 100 μg/kg of ICI 81008 and approx. 1 mg/kg of PGF_2α were used.In the majority of monkeys treated subcutaneously a rapid fall in circulating progesterone concentrations and earlier than normal menstrual bleeding occurred. When given per vaginam, ICI 81008 was as effective as when given subcutaneously, though PGF_2α was less effective intravaginally than by the subcutaneous route.     

Luteolysis induced in pigtail monkeys (Macaca nemestrina) with prostaglandin F2α, ICI 80996 and ICI 81008

Non-pregnant pigtail monkeys (M. nemestrina) were given ICI 80996 subcutaneously and ICI 81008 and PGF_2α subcutaneously or intravaginally, once daily on days 20–30 inclusive, or two or three times on days 24 or 26 only. Doses of 50 μg/kg of ICI 80996, 100 μg/kg of ICI 81008 and approx. 1 mg/kg of PGF_2α were used.In the majority of monkeys treated subcutaneously a rapid fall in circulating progesterone concentrations and earlier than normal menstrual bleeding occurred. When given per vaginam, ICI 81008 was as effective as when given subcutaneously, though PGF_2α was less effective intravaginally than by the subcutaneous route.     

The effect of the prostaglandin F2alpha analogue ICI 81008 on uterine small arteries and on blood pressure.

The effects of PGF2alpha and its analogue ICI 81008 have been compared on the small arteries of the omentum uteri on the rat. The vessels measured 20-80 mum in diameter and were examined by intra-vital-microscopy. While the maximum responses of PGF2alpha and ICI 81008 were similar, the duration of the effect of ICI 81008 was significantly longer (P is less than 0.001). At 15 minutes after the administration of the drugs the effect of ICI 81008 was still almost maximal, while the PGF2alpha response disappeared.     

Menstrual induction by the vaginal application of ICI 81008 gel

After ～2 weeks menstrual delay (positive Pregnosticon Tests) “menstrual induction” was attempted in 75 gravidas by repeated vaginal application of a gel, containing 200 or 400 μg/ml ICI 81008. After ～10 minutes, following the 1st vaginal delivery of 400 μg ICI 81008, the uterus responded to this PGF2α analogue with sustained contracture. The highest success rate in induced bleeding (93%) and pregnancy termination (79%), without supportive therapy, was achieved when 400 μg ICI 81008 was administered 2 to 5 times at 4 hour intervals. Those gravidas (21%), who failed in induced menstruation, or stopped bleeding within 24 hours after treatment, had positive Pregnosticon Tests on day 14 and were curetted. The side effects, mostly vomiting and increased blood pressure, were transient and subjectively and medically acceptable. While the vaginal application of the drug is apparently less effective than the intrauterine (1), it has the advantage of simple delivery and the potential of self-administration.     

Maintenance of pregnancy and levels of progesterone and relaxin in the serum of gilts following a stepwise reduction in the number of corpora lutea

The number of corpora lutea (CL) was reduced in pregnant gilts in a stepwise fashion. Eleven pregnant gilts were unilaterally ovariectomized at Day 30, leaving from 6 to 12 CL on the remaining ovary. At Day 40, the number of CL was again reduced by about half in each gilt and this was repeated on Day 50 until 1 to 3 CL remained. Blood was obtained to determine the level of progesterone in plasma on each day of surgery and 24 h later. Four gilts aborted; one had 1 CL and three had 2 CL. One gilt which had 1 CL resorbed the litter. The six gilts that maintained pregnancy from Day 50 to parturition had 1, 3, 2, 2, 2 and 2 CL, respectively. Gilts pregnant at Day 60 were also bled on that day and at 8-h intervals beginning 2 to 3 days prior to expected parturition at Day 114. At laparotomy on Day 50, gilts had from 3 to 20, nonluteinized follicles ranging from 12 to 20 mm in diameter. Hypertrophy of CL was not detected, nor were accessory CL formed. The level of progesterone in serum dropped significantly 24 h after surgery and rose to levels intermediate to pre- and postsurgery levels 10 days later. Parturition was uneventful and levels of relaxin and progesterone appeared normal.     

Changes in rat luteal ultrastructure and P450scc mRNA and protein content after in vivo treatment with a gonadotropin-releasing hormone agonist

Previous studies have demonstrated that plasma progesterone levels decrease in pregnant rats treated in vivo with a gonadotropin-releasing hormone agonist (GnRH-Ag), without changes in testosterone or estradiol levels in ovarian vein plasma. The objective of this study was to determine the loci of GnRH-Ag disruption of progesterone synthesis by examining luteal mitochondria, lipid droplets, cellular composition, and P450 side-chain cleavage (P450scc) enzyme and mRNA content in the pregnant rat. On Day 7 or 11 of pregnancy, osmotic minipumps containing GnRH-Ag were implanted into 5-7 rats. Sham operations were performed on 5-6 controls at each time period. Five micrograms per day of GnRH-Ag were released for about 24 h, after which corpora lutea and jugular vein plasma were collected. The corpora lutea were prepared for microscopy or analyzed for P450scc enzyme and mRNA content. Plasma progesterone levels were measured by RIA. In those rats treated with GnRH-Ag, progesterone levels had decreased, and within the luteal cells, there was an increase in the number of lipid droplets and a decrease in the number of tubular cristae within the mitochondria. Concomitantly, P450scc enzyme and mRNA content decreased on both Day 8 and Day 12 of pregnancy. Also, GnRH-Ag treatment decreased the ratio of large to small steroidogenic luteal cells on Day 8 of pregnancy, but did not alter cellular ratios on Day 12 of pregnancy. These observations suggest that treatment with GnRH-Ag inhibits progesterone synthesis by decreasing the amount of P450scc mRNA and enzyme content, which may alter the mitochondrial cristae structure on Day 8 and Day 12 of pregnancy. The reduction in tubular cristae and P450scc enzyme in the mitochondria may account for the increase in lipid droplets, as less cholesterol is converted to pregnenolone. An additional mechanism of inhibition may be the reduction in the number of large steroidogenic luteal cells, which appear to be the major source of progesterone in the rat corpus luteum on Day 8 of pregnancy.     

Oestrogenic effects of ICI 182,780, a putative anti-oestrogen,on the secretion of oxytocin and prostaglandin F2α during oestrous cycle in the intact ewe

The effect of ICI 182,780, oestrogen antagonist, on the concentrations of oxytocin and uterine PGF_2α was investigated in intact Border Leicester Merino cross ewes during the late oestrous cycle. Twelve cyclic ewes (n=6 per group) were randomly assigned to receive, at 6 h intervals, intra-muscular injection of either peanut oil or ICI 182,780 (1.5 mg kg⁻¹ day⁻¹) in oil for 2 days, starting at 1900 h on day 13 until 1300 h on day 15 post-oestrus. Hourly blood samples were collected via a jugular catheter from 0800 h on day 14 for 37 h and then daily over days 16, 17 and 18 post-oestrus. Peripheral plasma concentrations of oxytocin, the metabolite of prostaglandin F_2α, 15-keto-13,14-dihydro-prostaglandin F_2α, (PGFM) and progesterone were measured by radioimmunoassay. All ewes treated with ICI 182,780 exhibited functional luteal regression as indicated by a marked reduction in plasma progesterone concentrations to less than 1000 pg/ml over the period of 18–36 h during sampling period on days 14 and 15 of the oestrous cycle. In five of six vehicle-treated ewes, progesterone concentrations declined between day 16 and day 18 post-oestrus. In the remaining control ewe, progesterone concentrations reach less than 1000 pg/ml within 36 h of the commencement of the sampling period. During the frequent sampling period, the number of oxytocin pulses in the ICI 182,780 treated ewes was significantly higher compared to control ewes (2.7±0.3 vs. 0.8±0.3). The mean amplitude of oxytocin pulses observed was also greater (70.4±19.5 pg/ml) in ewes treated with ICI 182,780, but was not significantly different from control ewes (33.5±12.9 pg/ml). Oxytocin pulses may however have occurred following the initial two ICI 182,780 injections but before commencing blood sampling. The oxytocin pulses were detected at a mean of 3.2±0.2 h following each injection with ICI 182,780 during blood sampling. In the ICI 182,780-treated ewes, the pulsatile pattern of plasma PGFM in jugular blood samples over the 37 h sampling period on days 14 and 15 post-oestrus had a higher amplitude (512.9±158.9 vs. 121.7±78.7 pg/ml) and pulse area (618.1±183.3 vs. 151.5±102.9 (pg/ml)τ) compared to the vehicle-treated ewes (P<0.05) respectively. The average number of PGFM pulses observed per ewe was 3.0±0.7 in the ICI 182,780-treated group and was significantly (P<0.02) higher than the number of pulses (0.5±0.3) observed in ewes treated with vehicle alone. The PGFM pulses were detected at 4.2±0.6 h following each injection with ICI 182,780 during blood sampling. The percentage of PGFM pulses that occurred coincidently with a significant elevation of oxytocin concentrations was 44.4% in ICI 182,780-treated compared to 66.6% in control ewes. We conclude that administration of oestrogen antagonist ICI 182,780 accelerated development of the luteolytic mechanism by enhancing pulsatile secretion of oxytocin and PGFM which suggests that ICI 182,780 acts as an agonist for oxytocin and prostaglandin F_2α release in intact ewes when administered at 1.5 mg/kg/day over Day 13 to 15 post-oestrus.     

Prostaglandin induced early abortions in the bovine. Clinical outcome and endogenous release of prostaglandin F2α and progesterone

Peripheral blood plasma levels of progesterone and the main blood plasma metabolite of prostaglandin F_2α (15-keto-13, 14-dihydro-PGF_2α) were analysed in 12 heifers in which abortions were induced with a prostaglandin analogue (cloprostenol) at pregnancy stages from 39–146 days. All animals except one (treated on day 75 of pregnancy) aborted within 4 days following treatment.The peripheral plasma levels of progesterone decreased rapidly following the injection of cloprostenol. All heifers had shortlasting peaks of the prostaglandin metabolite in connection with luteal regression. In animals pregnant for less than 80 days this release ceased at the time of delivery of the fetuses, which were expelled within unruptured fetal membranes. Standing estrus was observed in connection with the expulsion of the fetuses. Two of the animals were mated at this estrus and became pregnant. In contrast, animals pregnant for more than 100 days released massive amounts of prostaglandin F_2α during a 2–5-days period post partum and had retained fetal membranes. No heat was observed in connection with these abortions. The animal that failed to abort showed no change in the prostaglandin metabolite levels.     

Therapeutic significance and the mechanism of action of the LH-RH agonist ICI 118630 in breast and prostate cancer

The influence of the LH-RH agonist ICI 118630 on circulating levels of the pituitary gonadotrophins LH and FSH and the gonadal steroids oestradiol, progesterone, 17-hydroxyprogesterone and testosterone has been studied in phase I clinical trials of the drug in patients with advanced breast or prostate cancer. ICI 118630 initially stimulated plasma levels of LH and FSH. On continued treatment however, the drug reversed this response and produced a rapid decline in plasma testosterone and progesterone in male and female patients respectively. Plasma oestradiol concentrations equivalent to those seen in oophorectomised or postmenopausal women were eventually produced in all 5 female patients treated with ICI 118630. In one patient however persistent follicular activity occurred until her third menstrual cycle. No appreciable side effects of the drug were observed. These data indicate that ICI 118630 initiates a castration-like endocrine response and has potential in the treatment of hormone dependent tumours of the breast and prostate.     

Progesterone is not responsible for the blood pressure fall in late-pregnant New Zealand genetically hypertensive rats

In various models of experimental and genetic hypertension in rats, blood pressure is markedly reduced during late pregnancy. The period during which the blood pressure reduction occurs is also the period when plasma progesterone is maximally elevated, and administration of progesterone to renal hypertensive rats has been reported to reduce blood pressure (J. Armstrong, 1959, Proc. Soc. Exp. Biol. Med. 102:452-455). To test the possibility that elevated plasma progesterone is responsible for the blood pressure reduction in late pregnancy, on Day 14 of pregnancy a group of New Zealand genetically hypertensive (NZGH) rats was ovariectomized and implanted with progesterone-filled capsules, to maintain plasma progesterone at low levels just sufficient to maintain pregnancy, and compared with intact, pregnant NZGH. Ovariectomy did not alter the characteristic course of blood pressure reduction seen in late-pregnant intact NZGH rats. In addition, daily administration of progesterone (15 mg/kg, sc) for 14 days did not alter blood pressure of either nonpregnant NZGH rats or New Zealand normotensive rats with chronic 1-kidney, 1-clip hypertension. It is concluded that blood pressure of NZGH rats is reduced to near normotensive levels in late pregnancy, as reported for other models of rat hypertension, but that elevated plasma progesterone levels are not requisite for that reduction and do not reduce blood pressure of renal hypertensive rats.     

Induction of daily PRL surges in rats by chronic treatment with progesterone

The effect of a high plasma progesterone level on the PRL releasing mechanism was investigated in rats of both sexes. Progesterone levels were maintained by implanting silicone tubes filled with the steroid. In the intact female, 6 progesterone tubes (inner diameter 2 mm; outer diameter 3 mm; length 40 mm) were implanted subcutaneously on the estrous day. With 2- to 5- day latent periods, the daily rise in the plasma PRL level was observed coincident with the time of nocturnal surge in the pseudopregnant rats induced by cervical stimulation. The same treatment applied to ovariectomized rats induced by cervical stimulation. The same treatment applied to ovariectomized rats induced diurnal and nocturnal surges. The peak height was lower in ovariectomized rats than that in intact or normal pseudopregnant rats, and was restored to almost the normal range by concomitant implantation of estradiol with progesterone. This latter protocol, however, did not induce any PRL surge in chronically orchidectomized rats. These results suggest that chronically elevated progesterone levels can induce such PRL surges as are observed in pseudopregnant rats, estradiol enhances the magnitude of the PRL surge, and the progesterone sensitive central mechanism, controlling the PRL surge, does not exist in adult male rats.     

Effects of estradiol and progesterone on early embryonic development in aging rats

Regularly cyclic, middle-aged female rats exhibit a decreased incidence of fertility, and those females that are fertile produce small litters. These decreases in fertility and litter size are associated with reduced numbers of normal blastocysts formed and implanted, suggesting that pre- and/or peri-implantation failures may be the causes for these aging-related reproductive declines. The present study examined the relationships and influence of circulating estradiol (E2) and progesterone (P) levels on early embryonic development and implantation in middle-aged rats. Serial blood samples obtained from cannulated, middle-aged pregnant rats revealed minor decreases in plasma P and increases in E2 levels during Days 2-4 of pregnancy, compared to young pregnant rats, resulting in significantly (p less than 0.001) decreased plasma P/E2 ratios. These alterations in endogenous hormone secretion in middle-aged pregnant rats were associated with fewer normal blastocysts on Day 5 of pregnancy and reduced numbers of normally implanting embryos. Correlation analysis further revealed a significant (p less than 0.05) inverse relationship between mean circulating E2 levels and numbers of normal conceptuses on Day 12 of gestation. Moreover, s.c. administration of P implants (in Silastic) to middle-aged pregnant rats increased serum P levels by about 34-40 ng/ml, and significantly (p less than 0.05) reduced the incidence of abnormal embryos before implantation. In contrast, treatment with E2 minipumps produced a sustained rise in serum E2 (by about 7-15 pg/ml) and resulted in the complete absence of embryos in the reproductive tracts by Day 5 of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myometrial activity and plasma progesterone and oxytocin concentrations in cycling and early-pregnant ewes

Myometrial activity and plasma progesterone (P) and oxytocin (OT) were measured in early pregnant (n = 5) and cycling (n = 5) ewes. Electromyography (EMG) leads and jugular and inferior vena cava (IVC) catheters were surgically placed in ewes about 1 wk before data collection. When ewes returned to estrus, they were bred to either an intact or vasectomized ram. Continuous EMG data were collected, and blood samples were collected twice daily from day of estrus (Day 0) until Day 18. Ewes bred with an intact ram were checked surgically for pregnancy on Day 20. Computerized, quantitative analysis of EMG events showed no difference in signal from the right to left uterine horns, and no differences between pregnant and cycling ewes (p less than 0.05) until Days 14-18 when nonpregnant ewes returned to estrus and had increased EMG activity. The mean number of EMG events 180-900 s in length decreased in pregnant ewes, but this difference was not significant (p less than 0.05). Jugular plasma progesterone (P) levels confirmed corpus luteum (CL) formation in all ewes, and no differences in P between pregnant and nonpregnant ewes were measured until Days 14-18, when cycling ewes underwent luteolysis and pregnant ewes maintained CL. IVC plasma oxytocin concentrations were increased in pregnant ewes compared to concentrations in nonpregnant ewes on Days 5-13 (p less than 0.05), and the difference was largest at Day 6 (means +/- SEM pg/ml: pregnant = 68.7 +/- 13.9, nonpregnant = 30.9 +/- 19.9).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of nutrition on the reproductive performance of Finn x Dorset ewes. I. Plasma progesterone and LH concentrations during late pregnancy.

Progesterone and LH concentrations were measured in the plasma of blood samples taken from forty-eight pregnant ewes on Days 100, 120 and 134 of gestation. The ewes, in two groups of twenty-four were maintained from Day 100 until parturition on two planes of nutrition which supplied daily energy and protein intakes of about 4-1 or 2-3 Mcal metabolizable energy and either 192 or 111 g digestible crude protein per ewe. Within the groups, the ewes carried one, two or three fetuses and the feed intake was adjusted according to litter size to produce a uniform nutritional state within the group. On Day 100, litter size affected the concentration of plasma progesterone (P less than 0-001), but had no effect on Days 120 or 134 when the ewes were fed according to litter size. The low feed intake however caused a significant increase in plasma progesterone concentrations. The LH concentrations showed no major changes during late pregnancy and no effect of nutrition or little size on the plasma hormone concentration was observed. It was concluded that the effect of litter size on plasma progesterone concentration recorded on Day 100 or gestation was partly mediated by level of nutrition.