Canine prostaglandin F2alpha receptor (FP) and prostaglandin F2alpha synthase (PGFS): molecular cloning and expression in the corpus luteum

In the dog luteolysis is not affected by hysterectomy. This observation led to the hypothesis that paracrine/autocrine rather than endocrine mechanisms of PGF2alpha are responsible for luteal regression in the dioestric bitch. The present experiments tested for the capacity of canine CL to produce and respond to PGF2alpha by qualitatively and quantitatively determining the expressions of PGFS, the enzyme converting PGH2 into PGF2alpha, and the PGF2alpha-receptor (FP) in CL of non-pregnant dogs during dioestrus. Canine PGFS and FP were isolated and cloned; both genes show a high homology (82-94%) when compared to those of other species. Relatively weak FP mRNA expression was detected on day 5 of dioestrus. It had increased by day 25 and remained constant thereafter. In situ hybridization (ISH) localized FP solely to the cytoplasm of the luteal cells, suggesting that these cells are the only luteal targets of PGF2alpha in this species. Only negative results were obtained for the expression of PGFS in canine CL by routine qualitative RT-PCR. When Real Time (TaqMan) PCR was applied, repetitively more negative than positive results were obtained at all timepoints. Any positive measurements observed at any point were neither repeatable nor related to the stage of dioestrus. This led us to conclude that expression of PGFS is either absent or present at very low level only. These data suggest that luteal regression in non-pregnant bitches is not modulated by PGF2alpha. However, the FP seems to be constitutionally expressed, explaining the receptivity of canine CL to exogenous PGF2alpha.     

Prostaglandin metabolism in the ovine corpus luteum: catabolism of prostaglandin F(2alpha) (PGF(2alpha)) coincides with resistance of the corpus luteum to PGF(2alpha)

To examine possible mechanisms involved in resistance of the ovine corpus luteum to the luteolytic activity of prostaglandin (PG)F(2alpha), the enzymatic activity of 15-hydroxyprostaglandin dehydrogenase (PGDH) and the quantity of mRNA encoding PGDH and cyclooxygenase (COX-2) were determined in ovine corpora lutea on Days 4 and 13 of the estrous cycle and Day 13 of pregnancy. The corpus luteum is resistant to the action of PGF(2alpha) on Days 4 of the estrous cycle and 13 of pregnancy while on Day 13 of the estrous cycle the corpus luteum is sensitive to the actions PGF(2alpha). Enzymatic activity of PGDH, measured by rate of conversion of PGF(2alpha) to PGFM, was greater in corpora lutea on Day 4 of the estrous cycle (P < 0.05) and Day 13 of pregnancy (P < 0.05) than on Day 13 of the estrous cycle. Levels of mRNA encoding PGDH were also greater in corpora lutea on Day 4 of the estrous cycle (P < 0. 01) and Day 13 of pregnancy (P < 0.01) than on Day 13 of the estrous cycle. Thus, during the early estrous cycle and early pregnancy, the corpus luteum has a greater capacity to catabolize PGF, which may play a role in the resistance of the corpus luteum to the actions of this hormone. Levels of mRNA encoding COX-2 were undetectable in corpora lutea collected on Day 13 of the estrous cycle but were 11 +/- 4 and 44 +/- 28 amol/microgram poly(A)(+) RNA in corpora lutea collected on Day 4 of the estrous cycle and Day 13 of pregnancy, respectively. These data suggest that there is a greater capacity to synthesize PGF(2alpha), early in the estrous cycle and early in pregnancy than on Day 13 of the estrous cycle. In conclusion, enzymatic activity of PGDH may play an important role in the mechanism involved in luteal resistance to the luteolytic effects of PGF(2alpha).     

Treatment with prostaglandin F2alpha increases expression of prostaglandin synthase-2 in the rat corpus luteum

Recent studies indicate that the corpus luteum (CL) may be a source of prostaglandin F2alpha (PGF2alpha) for regression. We investigated expression of mRNA and protein for prostaglandin G/H synthase (PGHS) in the CL of immature superovulated rats following administration of PGF2alpha. We observed an increase in mRNA for PGHS-2, the induced isoform, at 1 h and protein at 8 and 24 h after treatment. One hour after PGF2alpha, there was also a progressive decrease in plasma progesterone concentration. There were no changes, however, in expression of PGHS-1, the constitutive isoform, over the 24 h sampling period. These results indicate that PGHS-2 increases following PGF2alpha treatment and that expression of this enzyme in the rat CL may contribute to the luteolytic mechanism.     

Trypanosome-induced increase in prostaglandin F(2alpha) and its relationship with corpus luteum function in the goat

Plasma progesterone and 13,14-dihydro-15-keto Prostaglandin F(2alpha) (PGFM) were measured in normal (uninfected) and Trypanosoma congolense -infected adult goats for a period of 121 d, from May to August, during the breeding season in Kenya. Chronic trypanosomiasis rapidly increased the baseline plasma PGFM levels and the occurrence of irregular PGFM peaks in several infected goats. Progesterone luteal levels declined rapidly from the second and subsequent cycles post patency. Estrous cycles also became irregular but predominately shorter (8 to 19 d) before cessation from the second to fourth cycle following infection. The PGFM levels were still high during the acyclic period in all goats when progesterone levels were very low (1.4 to 2.4 nmol/l). The reciprocal increase in peripheral PGFM and decline in progesterone in these goats would suggest, in part, a trypanosome-induced PGF(2alpha) mediated luteolysis, and the possible involvement of prostaglandins in trypanosome-induced infertility in female goats.     

Response of the 1-5 day-aged ovine corpus luteum to prostaglandin F2alpha

The hypothesis that, in the ewe, prostaglandin (PG) F2alpha administration on day 3 after ovulation is followed by luteolysis and ovulation was tested using 24 animals. The ewes were treated with a dose of a PGF2alpha analogue (delprostenate, 160 microg) on days 1 (n=8), 3 (n=8) or 5 (n=8) after ovulation, was established by transrectal ultrasonography. Daily scanning and blood sampling were performed to determine ovarian changes and progesterone serum concentrations by radioinmunoassay. The treatment induced a sharp decrease of progesterone concentrations followed by oestrus and ovulation in all ewes treated on days 3 and 5 and in one ewe treated on day 1 (8/8, 8/8, 1/8; P<0.05). Seven ewes treated on day 1 did not respond to PGF2alpha treatment and had an inter-ovulatory cycle of normal length (17.4 +/- 0.5 days). However, the profile of progesterone concentrations during the cycle of these ewes was delayed 1 day (P<0.05) compared with a control cycle. The overall interval between PGF2alpha and oestrus for the 17 responding ewes was 42.4 +/- 2.3 h. In 15 of these ewes the ovulatory follicle was originated from the first follicular wave and the ovulation occurred at 60.8 +/- 1.8 h after PGF2alpha treatment. The other two responding ewes ovulated an ovulatory follicle originated from the second follicular wave between 72 and 96 h after treatment. These results support the hypothesis and suggest that refractoriness to PGF2alpha of the recently formed corpus luteum (CL) may be restricted to the first 1-2 days post-ovulation.     

Changes in corpus luteum content of prostaglandin F2 alpha and E in the adult pseudopregnant rat

Conflicting reports exist regarding the source of luteolytic PGF2 alpha in the rat ovary. To assess the quantities of different PGs, measurements of PGF2 alpha, PGE and PGB were performed by radioimmunoassay in the adult pseudopregnant rat ovary throughout the luteal lifespan. Ovaries of 84 rats were separated by dissection into two compartments, corpora lutea of pseudopregnancy and remainder of ovary. Tissue samples were homogenized and prostaglandins extracted and determined by radioimmunoassay. During the mid-luteal and late-luteal phases, levels of PGs were significantly higher in the corpora lutea of pseudopregnancy than in the remainder of ovary. An increase of PGF2 alpha-content in the corpus luteum was registered with peak-levels of 53.9 +/- 8.5 (mean +/- SEM, N = 18) ng/g tissue wet weight at day 13 of pseudopregnancy. PGE-levels reached peak-values at day 11 of pseudopregnancy (271.6 +/- 28.4 ng/g w w, mean +/- SEM, N = 12). PGB-levels were below detection limits in all compartments for all ages studied. The present study demonstrates increased availability of PGF2 alpha in the corpus luteum during the luteolytic period, and points toward either increased luteal synthesis or luteal binding of PGF2 alpha during the luteolytic period.     

Post-partum release of prostaglandin F(2alpha) and uterine involution in the cow

Peripheral plasma levels of the main blood plasma metabolite of PGF(2alpha) (15-keto-13,14-dihydro-PGF(2alpha)) and progesterone were investigated during the immediate, post-partum period in 59 normally calving cows. Uterine involution was monitored by weekly rectal palpations. The levels of the prostaglandin metabolite were high at parturition and remained thereafter elevated for periods varying up to 7-23 days. Uterine involution was completed during periods ranging from 16-53 days. According to the clinical findings, the animals were divided into three groups. Group A comprises 46 animals which had an uncomplicated, puerperal period. A significant (p<0.001) correlation between the duration of elevated prostaglandin levels and the time for completed uterine involution (Y=29.6 - 1.3 (X - 13.5)) was found for these animals. Group B animals (n=8) had periods of varying length with uterine discharge during the first 30 days post-partum. When compared to group A animals, the animals in group B had comparatively longer periods of prostaglandin release and also longer periods for completion of uterine involution. Group C animals (n=5) at times had palpable, thin-walled, cystlike structures in the ovaries during the first 30 days post-partum. In this group of animals, the periods of high prostaglandin levels, as well as for the completion of uterine involution, were similar to those for the animals in group A. Progesterone levels remained low during the immediate post-partum period and in no case were elevated levels found until the prostaglandin release had ceased.     

Changes in ovarian oxytocin secretion as an indicator of corpus luteum response to prostaglandin F(2alpha) treatment in cattle

Exogenous prostaglandin F(2alpha) (PGF(2alpha)) rapidly increases ovarian oxytocin (OT) release and decreases progesterone (P4) secretion in cattle. Hence, the measurement of OT secretion (the area under the curve and the height of the peak) after different doses of Oestrophan - PGF(2alpha) analogue (aPGF(2alpha)) on Days 12 and 18 of the estrous cycle (estrus = day 0), could be a suitable indicator of corpus luteum (CL) sensitivity to PGF(2alpha) treatment. Mature heifers (n = 36) were used in this study. Blood samples were collected from the jugular vein for the estimation of OT, P4 and 13, 14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM). In Experiment 1, different doses of aPGF(2alpha) (400, 300, 200 and 100 microg) given on Day 12 of the estrous cycle (n = 8) shortened (P < 0.05) the cycle duration (15.2 +/- 0.6 d) compared with that of the control (21.7 +/- 0.4 d). Successive heifers were also treated on Day 12 with 200 (n = 2), 100 (n = 2), 75 (n = 2) or 50 microg aPGF(2alpha) (n = 2). Only the 50 microg aPGF(2alpha) dose did not cause CL regression, although it increased OT concentrations to levels comparable to those observed during spontaneous luteolysis (50 to 70 pg/ml). In Experiment 2, on Day 18 of the cycle heifers (n = 8) were treated with 50, 40, 30 and 20 microg aPGF(2alpha). There was a dose-dependent effect of aPGF(2alpha) on OT secretion on Day 18 of the estrous cycle (r = 0.77; P < 0.05). In Experiment 3, an injection of 500 microg aPGF(2alpha) on Day 12 (n = 4) and 50 microg aPGF(2alpha) on Day 18 (n = 4) caused a similar (P > 0.05) increase in the OT concentration (288.5 +/- 23.0 and 261.5 +/- 34.7 pg/ml, respectively). Thus the effect of the same dose of aPGF(2alpha) (50 microg) on OT secretion was different on Days 12 and 18 of the cycle. To evoke similar OT secretion on Days 12 and 18 the dose of aPGF(2alpha) on Day 18 could be reduced 10-fold, confirming that CL sensitivity to PGF(2alpha) appears to increase in the late luteal phase.     

Expression and activation of protein kinase C isozymes by prostaglandin F(2alpha) in the early- and mid-luteal phase bovine corpus luteum

Western blotting was used to identify the array of protein kinase C (PKC) isozymes expressed in the early (Day 4) and midcycle (Day 10) bovine corpus luteum (CL). PCKalpha, betaI, betaII, epsilon, and micro isozymes were detected in total protein samples prepared from both Day-4 and Day-10 corpora lutea. In contrast, specific antibodies for PKCgamma, eta, lambda, and theta isozymes failed to detect protein bands in the luteal samples. PKCbetaII and epsilon isozymes were expressed differentially at these two developmental stages of the bovine CL. In the Day-4 luteal samples, PKCepsilon was barely detectable; in contrast, in the Day-10 samples, the actin-corrected ratio for PKCepsilon was 1.16 +/- 0.13. This ratio was higher than the detected ratio for PKCbetaI and micro at this developmental phase of the CL (P < 0.01), but it was comparable with the ratio detected for the PCKalpha and betaII. The amount of PKCbetaII was, although not as dramatic, also greater in the Day-10 CL (actin-corrected ratio was 0.85 +/- 0.2) than in the Day-4 CL (0.35 +/- 0.09 [P < 0.01]). The actin-corrected ratios for all other PKC isozymes, alpha (Day 4 = 0.93 +/- 0.16, Day 10 = 0.97 +/- 0.09), betaI (Day 4 = 0.54 +/- 0.073, Day 10 = 0.48 +/- 0.74), and micro (Day 4 = 0.21 +/- 0.042, Day 10 = 0.21 +/- 0.38) were not different at these 2 days of the cycle. An experiment was designed to test whether activation of specific isozymes differed between CL that do or do not regress in response to PGF(2alpha). Bovine CL from Day 4 and Day 10 of the estrous cycle were collected and 1 mm CL fragments were treated in vitro for 0, 2.5, 5, 10 or 20 min with PGF(2alpha) (0.1, 1.0, and 10 nM) or minimal essential medium-Hepes vehicle. Translocation of PKC from cytoplasm to membrane fraction was used as indication of PKC activation by PGF(2alpha). Evidence for PKC activation was observed in both Day-4 and Day-10 luteal samples treated with 10 nM PGF(2alpha). Therefore, if PKC, an intracellular mediator associated with the luteal PGF(2alpha) receptor, contributes to the lesser sensitivity of the Day-4 CL, it is likely due to the differential expression of the epsilon and betaII isozymes of PKC at this stage and not due to an inability of the PGF(2alpha) receptor to activate the isozymes expressed in the early CL.     

In vivo levels of prostaglandin F2 alpha, E2 and prostacyclin in the corpus luteum of pregnant and pseudopregnant rats

Prostaglandin F2 alpha (PGF2 alpha) is a well-known luteolytic factor in the rat corpus luteum. To investigate a possible luteal origin of PGF2 alpha, measurements of this prostaglandin were performed in different luteal tissues in vivo. Prostaglandin E2 (PGE2) and the stable metabolite of prostacyclin, 6-keto-PGF1 alpha, were assayed simultaneously. Corpora lutea of different ages from 57 pregnant and pseudopregnant rats (mated with sterile males) were rapidly excised, dissected in 0 degree C indomethacin solution, homogenized, and extracted for prostaglandins with solid-phase extraction cartridges. Prostaglandins were determined by radioimmunoassay. Plasma levels of progesterone and 20 alpha-dihydroprogesterone were also monitored. In the adult pseudopregnant rat model, luteolysis occurs at Day 13 +/- 1, and maximal levels of all three prostaglandins were detected on Day 13 of pseudopregnancy: 0.40 +/- 0.02, 2.6 +/- 0.29, and 1.76 +/- 0.24 pmol/mg protein (mean +/- SEM, n=7) for PGF2 alpha, PGE2, and 6-keto-PGF1 alpha respectively. In pregnant rats, on the corresponding day, levels were considerably lower: 0.15 +/- 0.02, 0.90 +/- 0.13, and 0.50 +/- 0.06 pmol/mg protein (mean +/- SEM, n=9, p less than 0.0001), respectively. Luteal levels in pregnant rats showed a continuous decline on Days 13 and 19 for all prostaglandins measured, whereas in pseudopregnant rats an increment of PGF2 alpha was noted between Days 7 and 13 and remained high on Day 19. PGE2 closely followed levels of PGF2 alpha, but at a 5- to 10-fold higher level. The coefficient of correlation between PGF2 alpha and PGE2 in the luteal compartment of both models was 0.87 (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of negative cooperativity among binding sites for prostaglandin F2alpha in bovine corpus luteum cell membranes.

The Scatchard analysis of equilibrium prostaglandin (PG) F₂α binding revealed that the binding was heterogeneous. The Hill plot of the same data had a slope of 0.68. This suggested that the heterogeneous nature of [³H] PGF₂α binding was either due to the presence of negative cooperativity or to the presence of two groups of independent binding sites. The kinetic experiments revealed that the presence of excess unlabeled PGF₂α in a diluting medium had no effect on dissociation rates at 25 fold dilution and it even retarded dissociation at higher dilutions. Furthermore, the observations that the low affinity PGF₂α binding sites can exist in the absence of high affinity binding sites and high affinity binding sites can be selectively abolished by treatment with N-ethylmaleimide suggest that negative cooperativity was not responsible for heterogeneous [³H] PGF₂α binding.     

Effect of early postpartum treatment with prostaglandin F2alpha on subsequent fertility in the dairy cow

Eighty Holstein dairy cows were treated with 25 mg of prostaglandin F2alpha (PGF2alpha) on Days 14 to 16 post calving. Eighty-four herd mates served as saline controls in the double blind study. The reproductive parameters used to measure fertility were mean days to first service on all cows and mean days open, first service conception rates and services per pregnancy on cows that became pregnant. Mean days to first service was similar in both groups (71.8 +/- 27, treated; 68.5 +/- 28.6, controls; P = 0.5352). The mean days open was 98.6 +/- 52.0 d for treated cows compared to 118.8 +/- 71.2 d for controls (P = 0.0680). First service pregnancy rates (treated, 41.3%; control, 35.7%) were not significantly different (P = 0.0630); however, the mean services per pregnancy (treated, 1.64; control, 2.33) were significantly (P = 0.0021) improved in the treated group. Ten cows in the treated group and twelve cows in the control group were diagnosed as having retained fetal membranes and/or metritis. For treated and control cows mean days to first service were 82.2 +/- 34.8 d and 82.8 +/- 58.7 d (P = 0.5652). Days open were 97.0 +/- 32.5 d and 133.4 +/-58.4 d (P = 0.3636); services per conception were 1.83 and 2.50 (P = 0.3178), respectively. In all treated cows reproductive parameters were similar whether cows had high serum progesterone ( > 1 ng/ml) or low serum progesterone ( < 1 ng/ml) on the treatment day. This study suggests that early postpartum treatment of lactating dairy cows with prostaglandin produces an improvement in fertility.     

Role of intraluteal prostaglandin F(2alpha), progesterone and oxytocin in basal and pulsatile progesterone release from developing bovine corpus luteum

The present study examined the role of intra-luteal prostaglandin (PG) F(2alpha), progesterone (P4) and oxytocin (OT) on the corpus luteum function by using specific hormone antagonists. Luteal cells from the developing CL (days 5-7 of the estrous cycle) were exposed to P4 antagonist (onapristone, OP, 10(-4)M), OT antagonist (atosiban, AT; 10(-6)M) or indomethacin (INDO; 10(-4)M), for 12h and then stimulated with PGF(2alpha) (10(-8)M) for 4h. Pre-treatment of the cells with OP, AT or INDO resulted in an increase in P4 secretion in response to PGF(2alpha). To examine the temporal effects of P4, OT and PGs on P4 secretion, dispersed luteal cells were pre-exposed to OP, AT or INDO for 1, 2, 4, 6 or 12h. Prostaglandin F(2alpha) stimulated P4 secretion (P<0.05) after 2h of pre-exposition. In the microdyalisis study, the spontaneous release of P4 from developing CL tissue was of pulsatile nature with irregular peaks at 1-2h intervals. Treatment with OP increased the number of P4 peaks (P<0.05), whereas AT and INDO significantly reduced the number of P4 peaks detected (P<0.05). Interestingly, INDO completely blocked the pulsatile nature in the release of P4, but it secretion remained stable throughout the experimental period. These results demonstrate that luteal PGF(2alpha), OT, and P4 are components of an autocrine/paracrine intra-ovarian regulatory system responsible for the episodic (pulsatile) release of P4 from the bovine CL during the early luteal phase.     

Positive association, in local release, of luteal oxytocin with endothelin 1 and prostaglandin F2alpha during spontaneous luteolysis in the cow: a possible intermediatory role for luteolytic cascade within the corpus luteum

Luteolysis is caused by a pulsatile release of prostaglandin F(2alpha) (PGF(2alpha)) from the uterus in ruminants, and a positive feedback between endometrial PGF(2alpha) and luteal oxytocin (OXT) has a physiologic role in the promotion of luteolysis. The bovine corpus luteum (CL) produces vasoactive substances, such as endothelin 1 (EDN1) and angiotensin II (Ang II), that mediate and progress luteolysis. We hypothesized that luteal OXT has an additive function to ensure the CL regression with EDN1 and Ang II, and that it has an active role in the luteolytic cascade in the cow. Thus, the aim of the present study was to observe real-time changes in the local secretion of luteal OXT and to determine its relationship with other local mediators of luteolysis. Microdialysis system (MDS) capillary membranes were implanted surgically into each CL of six cyclic Holstein cows (18 lines total among the six cows) on Day 15 (estrus == Day 0) of the estrous cycle. Simultaneously, catheters were implanted to collect ovarian venous plasma ipsilateral to the CL. Although the basal secretion of OXT by luteal tissue was maintained during the experimental period, the intraluteal PGF(2alpha) secretion gradually increased up to 300% from 24 h after the onset of luteolysis (0 h; time in which progesterone started to decrease). In each MDS line (microenvironment) within the CL, the local releasing profiles of OXT were positively associated with PGF(2alpha) and EDN1 within the CL in all 18 MDS lines implanted in the six CLs (OXT vs. PGF(2alpha), 50.0%; OXT vs. EDN1, 72.2%; P < 0.05). On the other hand, the intraluteal OXT was weakly related to Ang II (OXT vs. Ang II, 27.7%). In the ovarian vein, the peak concentration of PGF(2alpha) increased significantly when the peak of PGF(2alpha) coincided with the peak of OXT after the onset of spontaneous luteolysis (P < 0.05). In conclusion, intraluteal OXT may locally modulate secretion of vasoactive substances, particularly EDN1 and PGF(2alpha) within the CL, and thus might be one of the luteal mediators of spontaneous luteolysis in the cow.     

Patterns of gene expression in the bovine corpus luteum following repeated intrauterine infusions of low doses of prostaglandin F2alpha

Natural luteolysis involves multiple pulses of prostaglandin F2alpha (PGF) released by the nonpregnant uterus. This study investigated expression of 18 genes from five distinct pathways, following multiple low-dose pulses of PGF. Cows on Day 9 of the estrous cycle received four intrauterine infusions of 0.25 ml of phosphate-buffered saline (PBS) or PGF (0.5 mg of PGF in 0.25 ml of PBS) at 6-h intervals. A luteal biopsy sample was collected 30 min after each PBS or PGF infusion. There were four treatment groups: Control (n = 5; 4 PBS infusions), 4XPGF (4 PGF infusions; n = 5), 2XPGF-non-regressed (2 PGF infusions; n = 5; PGF-PBS-PGF-PBS; no regression after treatments), and 2XPGF-regressed (PGF-PBS-PGF-PBS; regression after treatments; n = 5). As expected, the first PGF pulse increased mRNA for the immediate early genes JUN, FOS, NR4A1, and EGR1 but unexpectedly also increased mRNA for steroidogenic (STAR) and angiogenic (VEGFA) pathways. The second PGF pulse induced immediate early genes and genes related to immune system activation (IL1B, FAS, FASLG, IL8). However, mRNA for VEGFA and STAR were decreased by the second PGF infusion. After the third and fourth PGF pulses, a distinctly luteolytic pattern of gene expression was evident, with inhibition of steroidogenic and angiogenic pathways, whereas, there was induction of pathways for immune system activation and production of PGF. The pattern of PGF-induced gene expression was similar in corpus luteum not destined for luteolysis (2X-non-regressed) after the first PGF pulse but was very distinct after the second PGF pulse. Thus, although the initial PGF pulse induced mRNA for many pathways, the second and later pulses of PGF appear to have set the distinct pattern of gene expression that result in luteolysis.     

Timing of prostaglandin F(2alpha) release episodes and oxytocin receptor development during luteolysis in the cow

The timing of PGF(2alpha) release and the timing and extent of the rise in endometrial oxytocin receptors was determined in relation to the timing of the progesterone fall during luteolysis in cycling cows. In cows undergoing luteolysis (n = 6), measurement of PGF(2alpha) metabolite in hourly plasma samples collected during daily 10 h sampling periods identified a total of 2.2+/-0.5 PGF(2alpha) release episodes per animal, each of 4.0+/-0.4 h duration. In cows in which luteolysis was not observed (n = 4) no PGF(2alpha) release episodes were identified. In a further three cows in which additional repeated uterine biopsies were collected on days 15, 17, 19, 21 and 23, endometrial oxytocin receptors were initially undetectable (<15 fmol/mg protein) but had increased to 120+/-19 fmol/mg protein prior to the initiation of PGF(2alpha) release episodes. Receptor concentrations then continued to increase reaching peak concentrations of 651+/-142 after luteolysis had been completed.     

The effect of intra-uterine prostaglandin F-2alpha on corpus luteum function in the human.

Prostaglandin F-2alpha (PGF-2alpha) was administered via a Foley catheter over a 12 hour period to 8 healthy volunteers awaiting laparoscopic sterilisation. The amount of PGF-2alpha infused varied between 500 mu-g and 2000 mu-g every 2 hours for 6 doses. Plasma progestins and oestradiol 17beta, and urinary estrogens and pregnanediol were assayed throughout the study period. There was no evidence of luteolysis in any patient although vaginal bleeding of varying duration occurred in all women within 36 hours of administration of PGF-2alpha.