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Biomedical subjects

G E Lamming

Publications and source records attributed to G E Lamming.

At least 55 records · Page 3Linked to original sources

The role of the endometrial oxytocin receptor in determining the length of the sterile oestrous cycle and ensuring maintenance of luteal function in early pregnancy in ruminants.

The oxytocin receptor, a seven transmembrane domain, G protein-linked receptor molecule, plays a central role in determining the endocrine function of the ruminant uterine endometrium. During nonpregnant cycles the control of this molecule by circulating steroid hormones leads to regression of the corpora lutea. The kinetics of the mechanisms involved determine the time at which luteolysis occurs, and therefore the length of the oestrous cycle. In pregnancy, secretions of the trophoblast block endometrial oxytocin receptor gene expression and lead to luteal maintenance. An understanding of the molecular mechanisms involved in the steroidal control of oxytocin receptor gene expression will provide an explanation for the relative constancy of oestrous cycle lengths in non-pregnant animals. Unravelling the way in which trophoblast products block expression of the oxytocin receptor gene will lead to a better understanding of the reasons for the high rate of embryonic loss in domestic ruminants.

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Quantitative control of oxytocin-induced PGF2 alpha release by progesterone and oestradiol in ewes.

The effect of oestradiol and progesterone concentrations on the uterine PGF2 alpha response to oxytocin was investigated by measuring 13,14-dihydro-15-keto PGF2 alpha (PGFM) secretion. One week after ovariectomy, 27 ewes were administered progestagen for 10 days followed by oestradiol for 2 days. Day 0 was designated as the time of the last 'oestrous' oestradiol injection. Six groups of ewes (n = 4) were then treated for 12 days with a high or low dose of progesterone (36 or 12 mg day-1) either alone or with a high or low dose of oestradiol (36 or 12 micrograms day-1) administered (in 1 ml of corn oil by i.m. injection, at intervals of 8 h) in a pattern designed to simulate a natural oestrous cycle profile. A control group (n = 3) was given corn oil alone. Ewes were treated with 1 microgram oxytocin (i.v.) on days 4, 8 and 12 of the simulated cycle and plasma was collected for assay of PGFM. An oxytocin-induced PGFM response occurred only on day 12, when the response was suppressed by high doses of progesterone and stimulated by high oestradiol doses. There was a significant effect of progesterone (P < 0.05) and a highly significant effect of oestradiol (P < 0.01) on the pattern of PGFM release in response to oxytocin. Low progesterone/high oestradiol stimulated the largest and most sustained increase in PGFM following oxytocin. There was a significant relationship between the oestradiol:progesterone ratio and the mean PGFM response on day 12 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Oestradiol concentration and the development of the uterine oxytocin receptor and oxytocin-induced PGF2 alpha release in ewes.

The control of temporal changes in oxytocin receptor concentrations and oxytocin-induced 13,14-dihydro-15-keto PGF2 alpha (PGFM) release was examined in ewes. One week after ovariectomy, 36 ewes were administered fluorogesterone acetate for 10 days followed by oestradiol (3 x 16 micrograms day-1) for 2 days (pretreatment cycle). Day 0 was designated as the time of the final 'oestrous' oestradiol injection. Ewes were then treated for up to 12 days with progesterone (24 mg day-1 maximum) with or without oestradiol (both hormones administered in 1 ml of corn oil i.m. at 8 h intervals) in a pattern known to simulate natural plasma profiles of the oestrous cycle. The three treatments were zero oestradiol, low oestradiol (12 micrograms day-1 maximum), and high oestradiol (36 micrograms day-1 maximum). Subgroups of four ewes from each treatment group were given 1 microgram of oxytocin (i.v.) on day 10, 11 or 12 of the simulated cycle, and endometrial oxytocin receptor concentrations were determined in samples collected within 3 h of oxytocin administration. On day 10 only one ewe in each group exhibited a PGFM response to oxytocin, and the mean response was unaffected by the concentration of oestradiol administered. On days 11 and 12 there was a significant effect of oestradiol concentration (P < 0.05) on the pattern of PGFM release in response to oxytocin, the high oestradiol concentration causing a rapid increase in the concentration of PGFM following oxytocin administration. On day 12 the oestradiol concentration was positively correlated with the PGFM mean response (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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The direct influence of the embryo on uterine PGF2 alpha and PGE2 production in sheep.

In unilateral pregnant ewes, obtained by surgically transecting one uterine horn to isolate it from the rest of the pregnant uterus, the isolated horn develops endometrial oxytocin receptors by day 16 despite being in a hormonal environment equivalent of that of a pregnant ewe. This study examines uterine prostaglandin production in these animals. On day 16 of pregnancy, ewes were anaesthetized and a uterine vein draining each horn and the jugular vein cannulated. Venous blood samples were taken at 10 min intervals for 1 h before and 1 h after an i.v. injection of oxytocin (1 microgram). Uterine vein samples were assayed for PGF2 alpha and PGE2 and jugular blood samples assayed for 13,14-dihydro,15-keto-PGF2 alpha. All ewes showed high plasma concentrations of 13,14-dihydro,15-keto-PGF2 alpha after the oxytocin injection. PGF2 alpha increased in the uterine vein draining the nonpregnant transected horn of a unilaterally pregnant ewe following oxytocin treatment, whereas there was no increase in concentration in plasma draining the pregnant horn. Basal plasma PGF2 alpha concentrations from the uterine vein draining the pregnant horn were significantly higher than concentrations obtained from the uterine vein of the transected horn while PGE2 concentrations did not vary between the two horns. After oxytocin injection, there was a significant increase in plasma PGE2 concentration in venous blood collected from both sides.(ABSTRACT TRUNCATED AT 250 WORDS)

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Potential synergism between platelet-activating factor and alpha 1-recombinant interferon in promoting luteal maintenance in cyclic ewes.

In sheep, the presence of an embryo in utero on the 12th to 13th day after oestrus prevents luteolysis. These studies investigated whether platelet-activating factor (PAF) could exert an antiluteolytic function, either alone or in combination with interferon. The intrauterine administration of 250 micrograms PAF per horn per day, administered through indwelling cannulae into the uterus as injections twice a day (n = 12) or by continuous infusion (n = 4) failed to extend luteal function compared with controls (n = 8). When indwelling cannulae were used to administer (i) 125 micrograms PAF per uterine horn, as a bolus infusion twice a day (n = 5), (ii) continuous infusion of 500 micrograms bovine recombinant alpha 1-interferon each day (brIFN, n = 5), (iii) 125 micrograms PAF per horn twice a day, plus 500 micrograms brIFN per day (n = 8), or (iv) vehicle (n = 5), the luteal phase was significantly longer in co-infused (iii) than in control (iv) animals. These findings indicate that pharmacological doses of PAF may act synergistically with interferons to prevent luteolysis.

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Plasma and luteal concentrations of oxytocin in cyclic and early-pregnant cattle.

Concentrations of oxytocin were measured in corpora lutea obtained from heifers throughout the oestrous cycle and first 30 days of pregnancy. Values were low during the first 3 days of the cycle (less than 250 ng/g tissue), increasing to 1312 ng/g by Day 4. Values then further increased up to a maximum of 2344 ng/g on Day 12. Concentrations were similar in cyclic and pregnant animals throughout the midluteal phase and were maintained at approximately 1500 ng/g until the 18th (cyclic cows) or 19th (pregnant cows) day after oestrus, when they were again low. Values subsequently remained less than 250 ng/g in pregnant cattle. Concentrations of oxytocin in jugular venous plasma of cyclic (n = 5) and pregnant (n = 4) cows were measured in samples collected every 15 min for 8 h on Days 14, 16, 18 and 19 after oestrus. There were no significant differences in mean concentrations (range: 2.5-4.7 pg/ml) or in the number, frequency or area under the curve of episodes between either cyclic and pregnant animals, or between days. Mean basal concentrations were higher on Day 16 than on Day 14 (P less than 0.05), values on Days 18 and 19 being intermediate. These findings suggest that the corpus luteum contains a finite amount of releasable oxytocin, which is exhausted by Day 18-19 after oestrus, whether or not pregnancy occurs, and that there is no further accumulation of oxytocin in the animal during early pregnancy. The contribution of luteal oxytocin to jugular venous concentrations appears to be less than in sheep, in which values in the jugular vein closely parallel those within the corpus luteum.

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Administration of recombinant bovine interferon-alpha I at the time of maternal recognition of pregnancy inhibits prostaglandin F2 alpha secretion and causes luteal maintenance in cyclic ewes.

The antiluteolytic protein, ovine trophoblast protein-1, which is secreted by sheep embryos at about the time of the maternal recognition of pregnancy, exhibits significant structural homology with alpha interferons. Experiments were conducted to examine the effects of intra-uterine and systemic administration of a recombinant bovine interferon-alpha I (rboIFN-alpha I) upon the interoestrus interval, endometrial oxytocin receptor concentrations and secretion of prostaglandin (PG) F2 alpha in cyclic ewes. In Expt 1, each ewe had a cannula placed in the tip of a uterine horn ipsilateral to a corpus luteum, 7 days after an induced oestrus. From day 9 after oestrus until day 19, ewes received either 200 (n = 4), 667 (n = 5) or 2000 (n = 9) micrograms/24 h of rboIFN-alpha I, meclofenamic acid (n = 4) or vehicle (n = 11). Other ewes received 2000 micrograms rboIFN-alpha I/24 h (n = 5) between days 12 and 15 only. All ewes were killed on day 19. Mean luteal phase, as determined by daily plasma progesterone measurements, was significantly longer (P less than 0.01) and mean concentrations of 13,14-dihydro-15-keto PGF 2 alpha (PGFM) in plasma were lower (P less than 0.05) in ewes receiving 667 or 2000 micrograms rboIFN-alpha I between days 9 and 19, or 2000 micrograms between days 12 and 15, than in animals from other treatment or control groups. A similar protocol was used in Expt 2, in which further ewes received either 2000 micrograms rboIFN-alpha I/24 h (n = 5) or vehicle (n = 5) by bolus infusions twice a day into one uterine horn. Mean luteal phase was significantly (P less than 0.05) longer in treated than in control animals, but differences in PGFM concentrations were not significant. In Expt 3, after a synchronized oestrus, ewes received either 2.5 mg rboIFN-alpha I by i.m. injection twice a day between days 12 and 15 (n = 10), 2.5 mg rboIFN-alpha I by i.m. injection twice a day between days 9 and 15 (n = 11), i.m. injection of vehicle alone twice a day (n = 20), or continual intra-uterine infusion of 2 mg rboIFN-alpha I/day between days 12 and 15 (n = 7). The mean luteal phase of ewes receiving rboIFN-alpha I by intrauterine infusion or i.m. injection between days 9 and 15 was significantly longer than for animals from the other two groups (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

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Role of the oxytocin receptor in the choice between cyclicity and gestation in ruminants.

The endometrial oxytocin receptor occupies a central point in the choice between luteolysis and pregnancy in ruminants. Receptor expression determines the time at which luteolysis occurs in nonpregnant animals, and thereby determines the duration of the oestrous cycle. Inhibition of receptor expression by trophoblast interferon (IFN) blocks the process of luteal regression and leads to continued progesterone secretion and the successful growth of the conceptus. Trophoblast IFN is probably required from the time of normal luteolysis during the cycle until luteal oxytocin concentrations of pregnancy decline, thus removing the stimulatory mechanism for the release of the episodes of prostaglandin F2 alpha required for luteolysis.

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Experimental and practical approaches to the establishment and maintenance of pregnancy.

A series of three large field trials was carried out to assess the effect of buserelin on fertility in dairy cows. In the first, 10 micrograms buserelin was injected on the day of insemination. There were no significant effects on fertility parameters compared to untreated controls. In the second trial cows were injected on day 12 after insemination. Mean pregnancy rates to first insemination were 53.4 and 65.4% for control and treated cows respectively (P < 0.01). Mean pregnancy rates to repeat inseminations were 52.9 and 59.4% for control and treated cows (NS). Mean calving to conception intervals were 91.4 and 85.3 days (P < 0.01) and the incidence of barren cows was 10.2 and 5.3% (NS). Overall the economic benefit of buserelin injection on day 12 was calculated to be 27.43 pounds per cow treated excluding the cost of the treatment. In trial 3 cows were injected with buserelin either on day 8 or 10 after insemination. There were no significant effects on fertility parameters compared to untreated control cows. In a fourth trial ewes were injected with 4 micrograms buserelin on day 12 after service. There were indications that both pregnancy rate and lambing percentage could be increased by buserelin treatment. Daily blood samples were collected from 5 dairy cows during a control cycle and a cycle in which 10 microgram buserelin was injected on days 11 and 13. Cycle length was unaffected by treatment and the concentration and pattern of progesterone secretion did not differ between control and treated cycles. Plasma oestradiol concentrations were similar in the control and treated cycles before day 11. However from day 12 to 16, equivalent to the time of maternal recognition of pregnancy, the mean concentration of oestradiol was significantly reduced in the treated cycle. As oestradiol stimulates both the development of uterine oxytocin receptors and the secretion of PGF2 alpha we suggest that any improvement in pregnancy rate after buserelin is due to a weakened luteolytic mechanism, resulting from a lower plasma oestradiol concentration.

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Uterine oxytocin receptors in cyclic and pregnant cows.

Binding of [3H]oxytocin to uterine subcellular preparations ('oxytocin receptor concentrations') was measured in uterine tissue of heifers and multiparous dairy cows at various stages of the oestrous cycle and during early pregnancy. A method for the assay of ovine uterine oxytocin receptors was optimized for use on bovine tissue. Oxytocin receptor concentrations were increased in cyclic animals around the period of luteolysis and oestrus, rising on Day 15 in endometrium and on Day 17 in myometrium while pregnant animals showed no comparable rise. Receptor concentrations then declined on Day 3 after oestrus in myometrium and on Day 5 in endometrium. Some cyclic animals did not show the expected rise in receptors in the late luteal phase; these animals had abnormally high progesterone concentrations for this stage of the cycle. In animals slaughtered on Day 18 after oestrus and/or insemination which had low oxytocin receptor levels, plasma progesterone concentrations were consistently high; while all animals showing the late luteal phase elevation in receptor values had low progesterone concentrations. Oxytocin receptor and progesterone concentrations were negatively correlated (P less than 0.05). These data support the hypothesis that oxytocin receptor level is a key factor in the process of luteolysis in cattle and that in pregnancy there is suppression of uterine oxytocin receptor at the expected time of luteolysis. We suggest that uterine oxytocin receptor levels are partly controlled by circulating steroid hormones and are suppressed during early pregnancy.

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A low molecular weight endometrial secretory protein which is increased by ovine trophoblast protein-1 is a beta 2-microglobulin-like protein.

Ovine trophoblast protein-1 (oTP-1), stimulates the secretion of several proteins in explant culture of day-12 cyclic ovine endometrium. We partially purified and identified one of these proteins, an 11,000 Mr, pI approx. 6 protein by N-terminal amino acid sequencing and immunoprecipitation using antibody to human beta 2-microglobulin. The protein was purified from cultures of endometrium collected from day-16 pregnant ewes. The N-terminal amino acid sequence was 40-55% homologous to beta 2-microglobulin from a variety of species. Antibody to human beta 2-microglobulin immunoprecipitated the protein and another protein of similar molecular weight but more acidic pI. Using immunoprecipitation of radiolabelled proteins from culture, we demonstrated that oTP-1 increased production of this protein by 40% (P less than 0.05). We conclude that oTP-1 increases the secretion of a beta 2-microglobulin-like protein from day-12 non-pregnant endometrium in culture.

Amino Acid Sequence↗

Ovine conceptus secretory proteins and bovine recombinant interferon alpha (1)-1 decrease endometrial oxytocin receptor concentrations in cyclic and progesterone-treated ovariectomized ewes.

A series of experiements was performed to determine whether proteins produced by the sheep conceptus (oCSP) during the time of maternal recognition of pregnancy or bovine recombinant interferon alpha 1-1 (brIFN) decrease oxytocin receptor concentrations in the endometrium of cyclic or ovariectomized progesterone-treated ewes. In experiment 1, cyclic ewes received intrauterine infusions of serum proteins (oSP), oCSP or brIFN on days 12, 13 and 14 of the oestrous cycle. Ewes then received an oxytocin challenge (1 microgram in 0.9% NaCl), and blood samples were taken just before and every 10 min for 1 h after the challenge; these were measured for 13,14-dihydro-15-ketoprostaglandin F 2 alpha (PGFM), the stable metabolite of prostaglandin F 2 alpha. Endometrial oxytocin receptor concentrations were then measured. The oCSP and brIFN treatments suppressed both endometrial oxytocin receptor concentrations and oxytocin-induced increases in PGFM concentrations. In experiment 2, ewes were ovariectomized and then pretreated with a fluorogestone acetate-releasing intravaginal device for 10 days followed by oestradiol (25 micrograms i.m. twice daily for 2 days). Ewes were then treated with progesterone (10 mg i.m. twice daily for 12 days). Ewes received intrauterine infusions of oSP, oCSP and brIFN on days 10, 11 and 12 of progesterone treatment. On the day after the last progesterone treatment, ewes were challenged with oxytocin and blood samples collected to measure PGFM. Endometrial oxytocin receptors were also measured. Treatment with oCSP, but not brIFN, suppressed endometrial concentrations of oxytocin receptor, and neither oCSP nor brIFN altered oxytocin-induced increases in PGFM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

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Molecular biology of trophoblast interferons and studies of their effects in vivo.

Southern blotting of bovine genomic DNA indicated the presence of at least 3 bovine tIFN genes. The full DNA sequence of one of these genes, thought to be expressed in trophoblast, has been determined, including 193 bp of 5' non-coding region. The inferred amino acid sequence of bovine tIFN is more similar to ovine tIFN (80%) than to bovine IFN-alpha II (70%). The 5' flanking sequence has some similarity with bovine IFN-alpha II, and may contain a viral response element. A recombinant bovine alpha I interferon (Ciba Geigy; brIFN), resembling tIFN, extended oestrous cycle length in sheep when administered by intrauterine infusion over the period, Days 12-15 after oestrus, when maternal recognition of pregnancy occurs. Intramuscular injection was only effective at the doses used if given over a longer period (i.e. Days 9-15). Our experiments indicate that both tIFN and brIFN inhibit luteolysis by preventing a rise in endometrial oxytocin receptor concentrations, and suggest that tIFN achieves this by extending the time for which progesterone suppresses oxytocin receptor development. Further studies are required to confirm this hypothesis and to elucidate the interaction of the effects of progesterone and tIFN in endometrial cells.

Amino Acid Sequence↗

Luteal inadequacy during the early luteal phase of subfertile cows.

A study was made of early luteal function (up to Day 6) in cyclic and pregnant heifers and also in older, subfertile cows. There were no differences in vivo or in vitro between cyclic and pregnant heifers, indicating no luteotrophic effect of the embryo at this stage, but the increase in postovulatory peripheral progesterone concentrations was delayed (P less than 0.01) and occurred more slowly (P less than 0.001) in the subfertile cows than in the heifers. The corpora lutea of the subfertile cows were heavier (P less than 0.001) than those of the heifers on Day 6. Basal progesterone production by dispersed luteal cells was similar between heifers and subfertile cows, but there was a difference (P less than 0.001) in the pattern of response to exogenous LH and PGE-2. Cells from subfertile cows were less sensitive to the stimulatory effects of PGE-2 and although LH increased (P less than 0.001) progesterone production by all cells, this stimulation by a low dose of LH was inhibited by PGE-2 in luteal cells from subfertile cows. This effect did not occur in the luteal cells from heifers. These results indicate the possibility that luteal inadequacy, due to a diminished response to circulating luteotrophic hormones, may contribute to embryo mortality in subfertile cows.

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Prostaglandin E-2 as a potential luteotrophic agent during early pregnancy in cattle.

Heifers slaughtered on Day 18/19 of pregnancy had significantly higher (P less than 0.001) concentrations of PGE-2 (measured as its methyl oxime) in uterine flushings than did animals slaughtered on Days 6 or 12 of pregnancy, or on Days 6 or 12 of the oestrous cycle. In addition, concentrations were higher in the uterine horn ipsilateral to the corpus lueum on Days 12 (P less than 0.05) and 18/19 (P less than 0.01) than in the contralateral horn. Incubation of dispersed luteal cells for 3 h with LH (0.1 or 100 ng/ml) and/or PGE-2 (0.01-1000 ng/ml) in vitro showed no differences in basal progesterone production or in the responses to exogenous hormones between pregnant and non-pregnant cattle. However, low doses of PGE-2 (0.01-10 ng/ml) inhibited the stimulation of progesterone secretion by the lower dose of LH. These findings indicate that although PGE-2 can stimulate progesterone synthesis by luteal cells it may also have inhibitory effects, and therefore its role in pregnancy requires further definition.

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Interrelationships between progesterone, 13,14-dihydro-15-keto PGF-2 alpha (PGFM) and LH in cyclic and early pregnant cows.

Plasma progesterone and LH secretion patterns were examined in 18 mature dairy cows during the oestrous cycle and after insemination. Blood samples were collected every 15 min for 8 h per day on Days 3, 5, 6, 7, 8, 9, 10, 12, 14, 16, 17, 18, 19, 20 and 21 of the oestrous cycle, then, in the same cows, at the same times during early pregnancy. PGF-2 alpha secretion rates (as determined by plasma PGFM concentrations) were also monitored on Days 14, 16 and the day of, or equivalent to, luteal regression. Mean daily plasma progesterone concentrations were similar until Day 16 in cyclic and pregnant cows, after which values in non-pregnant animals declined. Regression analysis indicated that progesterone concentrations were best described by a quadratic expression with fitted maximum values on Day 13 in non-pregnant animals but values increased linearly over the whole period to Day 21 in pregnant cows. The frequency, amplitude and area under the curve of LH episodes showed no significant differences between cyclic and pregnant animals. In pregnant cows, the amplitude and area under the curve of progesterone episodes increased linearly between Days 8 and 21, although no such increase occurred in cyclic cows. Low-level PGFM episodes were present in cyclic and pregnant cows on Days 14 and 16 after oestrus, and high amplitude episodes occurred in non-pregnant cows during luteal regression. Pregnant cows showed a significant depression of the amplitude, but not the frequency of episodes at the expected time of luteal regression. These results confirm that the corpus luteum of pregnancy secretes an increasing amount of progesterone per se and per unit of LH until at least Day 21 after mating. They further suggest that the corpus luteum of the cyclic cow may experience small episodes of PGF-2 alpha and be subjected to initial degenerative changes by Day 14 after oestrus, some time before the onset of definitive luteolysis.

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Comparison of oxytocin/prostaglandin F-2 alpha interrelationships in cyclic and pregnant cows.

The secretion of prostaglandin (PG) F-2 alpha in response to intravenous injection of 100 i.u. oxytocin on Day 18 after oestrus was determined by measuring jugular venous concentrations of 13,14-dihydro-15-keto PGF-2 alpha (PGFM) in 7 pregnant, 6 cyclic and 2 inseminated non-pregnant heifers. Two other heifers received i.v. saline (controls). The immediate responses of pregnant heifers were smaller than in non-pregnant animals (P less than 0.05), as were baseline concentrations in the post-response period (P less than 0.05). Endometrial oxytocin receptor concentrations were higher in nonpregnant than pregnant heifers (P less than 0.05), but PGFM response to oxytocin challenge was not correlated with oxytocin receptor concentration. Oxytocin receptor concentrations on Day 18 were positively correlated with those of plasma oestradiol on Day 17 (P less than 0.01) and inversely with plasma progesterone concentrations on Day 18 (P less than 0.01). These findings confirm that PGF-2 alpha secretion in response to oxytocin challenge is attenuated in pregnant animals on the 18th day after oestrus and that, while the prevailing steroid environment is of importance in inducing oxytocin receptor activity, the secretion of PGF-2 alpha is not subsequently limited by oxytocin receptor numbers. The quantities of PGE-2, PGFM and PGF-2 alpha recovered in uterine flushings taken from heifers on Day 18 were greater in pregnant than other animals (P less than 0.01, P less than 0.05, P less than 0.001, respectively). Intrauterine concentrations of PGF-2 alpha and PGFM were not correlated with the plasma PGFM responses.

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Control of endometrial oxytocin receptor and uterine response to oxytocin by progesterone and oestradiol in the ewe.

The effects of administration of progesterone and oestradiol on ovine endometrial oxytocin receptor concentrations and plasma concentrations of 13,14-dihydro-15-keto prostaglandin F-2 alpha (PGFM) after oxytocin treatment were determined in ovariectomized ewes. Ewes received progestagen pre-treatment, progesterone and/or oestradiol in 11 different treatment schedules. Progestagen pre-treatment decreased oxytocin receptor concentrations in endometrium from ewes treated subsequently with either progesterone for 5 days or progesterone for 5 days plus oestradiol on Days 4 and 5 of progesterone treatment. Oestradiol increased endometrial oxytocin receptor concentrations when administered on Days 4 and 5 of 5 days progesterone treatment. Progestagen pre-treatment followed by progesterone treatment for 12 days caused a large increase in oxytocin receptors and no further increase occurred when ewes were given oestradiol on Days 11 and 12, or when progesterone was withdrawn on Days 11 and 12, or these two treatments were combined. Oxytocin administration caused an increase in plasma PGFM concentrations in ewes which did not receive progestagen pre-treatment, and subsequently received progesterone treatment for 5 days and oestradiol treatment on Days 4 and 5 of progesterone treatment. Similarly treated ewes which received progestagen pre-treatment did not respond to oxytocin. Oxytocin administration also increased plasma PGFM concentrations in ewes which received progestagen pre-treatment followed by progesterone treatment for 12 days, progesterone treatment for 12 days plus oestradiol on Day 11 and 12 of progesterone treatment, progesterone withdrawal on Day 11 and 12, or progesterone withdrawal and oestradiol treatment combined. The results indicate that (1) progesterone pre-treatment affects oxytocin receptor concentrations in the endometrium and uterine responsiveness to oxytocin and (2) progesterone treatment alone for 12 days after a treatment which mimics a previous luteal phase and oestrus is sufficient to induce oxytocin receptors and increase oxytocin-induced PGF release. These results emphasize the importance of progesterone and provide information which can be used to form an hypothesis for control of luteolysis and oestrous cycle length in the ewe.

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