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Flunixin meglumine (FM; 2.5 mg/kg) was given to heifers at three 8-h intervals, 16 d after ovulation (first treatment = Hour 0) to inhibit the synthesis of prostaglandin F(2α) (PGF), based on plasma concentrations of a PGF metabolite (PGFM). Blood samples were collected at 8-h intervals from 15 to 18 d in a vehicle (control) and FM group (n = 16/group). Hourly samples were collected from Hours -2 to 28 in 10 heifers in each group. Heifers that were in preluteolysis or luteolysis at Hour 0 based on plasma progesterone (P4) concentrations at 8-h intervals were partitioned into subgroups. Concentration of PGFM was reduced (P < 0.05) by FM treatment in each subgroup. For the preluteolytic subgroup, the first decrease (P < 0.05) in P4 concentration after Hour 0 occurred at Hours 24 and 40 in the vehicle and FM groups, respectively. Plasma P4 concentrations 32 and 40 h after the beginning of luteolysis in the luteolytic subgroup were greater (P < 0.05) in the FM group. Concentration at the peak of a PGFM pulse in the FM group was greater (P < 0.05) in the luteolytic than in the preluteolytic subgroup. The peak of a PGFM pulse occurred more frequently (P < 0.001) at the same hour as the peak of an LH fluctuation than at the ending nadir of an LH fluctuation. In conclusion, a reduction in prominence of PGFM pulses during luteolysis delayed completion of luteolysis, and treatment with FM inhibited PGFM production more during preluteolysis than during luteolysis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Acute changes in circulating progesterone concentration and luteal blood flow in heifers after a conventional dose of prostaglandin F(2α) (PGF; 25mg dinoprost, i.m.) were compared between the early luteal phase (Day 3) and midluteal phase (Day 10; Day 0=ovulation), using four groups (Day-3 control, Day-3 PGF, Day-10 control, and Day-10 PGF; n=6 heifers/group). Blood samples were collected at 0, 2, 5, 10, 15, 30, 60, and 120 min (0 min=treatment). Percentage of luteal area with color-Doppler blood-flow signals was estimated at 0, 10, and 30 min. In the Day-3 and Day-10 PGF groups, progesterone increased to a peak at 15 min. In the Day-3 PGF group, progesterone decreased to the pretreatment concentration by 60 min but did not decrease to below the pretreatment concentration during the 2-h experimental period. In the Day-10 PGF group, progesterone decreased to below pretreatment concentration by 30 min, indicating a luteolytic response. In the Day-3 and Day-10 PGF groups, luteal blood flow increased within 10 min and remained elevated until the last examination at 30 min. The absence of a decrease in progesterone to below pretreatment concentrations in the Day-3 PGF group indicated that luteolysis does not necessarily follow a transient increase in progesterone and a concomitant increase in luteal blood flow. The immediate transient increase in progesterone and an increase in luteal blood flow without a subsequent decrease in progesterone to below pretreatment concentrations after PGF treatment in early luteal-phase heifers are novel findings., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Novel characterization of the transition between preluteolysis and luteolysis was done in seven heifers. Blood samples were collected hourly and assayed for progesterone (P4), 13-14-dihydro-15-keto-PGF2α (PGFM), and estradiol (E2). The peaks of P4 oscillations were used to designate the transitional hour in each heifer. The interval from the peak of the last PGFM pulse of preluteolysis to the peak of the first pulse during luteolysis (transitional period) was longer (P < 0.0001) than the interval between the first and second pulses during luteolysis (13.4 ± 1.3 h vs. 7.0 ± 0.9 h). The long intervals from the last PGFM pulse of preluteolysis to the transitional hour (4.0 ± 0.9 h) and from the transitional hour to the first PGFM pulse of luteolysis (9.4 ± 1.3 h) resulted in the illusion that the beginning of luteolysis was not associated temporally with a PGFM pulse. The E2 and PGFM concentrations were less (P < 0.05) during the last PGFM pulse of preluteolysis than during the first pulse of luteolysis. Concentration of P4 was suppressed at the peak of the last PGFM pulse of preluteolysis and consistently rebounded at the transitional hour to the concentrations before the PGFM pulse. In four of seven heifers, one or two P4 rebounds occurred between the peak of the PGFM pulse and the rebound at the transitional hour. Results indicated that the prolonged transitional period may be related, at least in part, to increasing concentration of E2, intervening P4 rebounds between the peak of the last PGFM pulse of preluteolysis and the transitional hour, and the complete P4 rebound at the transitional hour., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Plasma from hourly blood samples from two previous studies in heifers was assayed for hormones that were not considered in the previous reports. The objective was to determine the intrapulse temporal relationships between a prostaglandin F2α metabolite (PGFM) pulse and various hormones during preluteolysis and luteolysis. Hormone concentrations were centralized to the peak of a PGFM pulse (Hour 0) and evaluated from Hours -3 to 3. Experiment 1 (n=6) was done during early luteolysis. Progesterone decreased during Hours -3 to 0 and then rebounded, but did not return to prepulse concentrations, and concentration of LH increased between Hours -1 and 2. In Experiment 2 (n=7), comparisons were made between the last PGFM pulse of preluteolysis and the first pulse of luteolysis. Intrapulse concentrations of LH increased rapidly between Hours 0 and 1 during preluteolysis and gradually between Hours -2 and 2 during luteolysis. Intrapulse differences in cortisol among hours were not significant for preluteolysis and approached significance (P<0.06) during luteolysis, owing primarily to an apparent increase between Hours -2 and 1. Oxytocin concentrations showed only an hour effect (P<0.0003) from to an increase between Hours -2 and 0 and a decrease between Hours 0 and 2. Results indicated that oxytocin and PGFM concentrations increased and decreased concomitantly and supported the hypothesis that the reported more prominent rebound in progesterone during the descending portion of a PGFM pulse during preluteolysis than during luteolysis involves a greater transient increase in LH., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Pulses of the prostaglandin F(2α) (PGF) metabolite 13,14-dihydro-15-keto-PGF(2α) (PGFM) and the intrapulse concentrations of progesterone were characterized hourly during the preluteolytic, luteolytic, and postluteolytic periods in seven heifers. The common hour of the end of preluteolysis and the beginning of luteolysis was based on a progressive progesterone decrease when assessed only at the peaks of successive oscillations. The end of the luteolytic period was defined as a decrease in progesterone to 1 ng/mL. Blood samples were taken hourly from 15 d after ovulation until luteal regression as determined by color-Doppler ultrasonography. Between Hours -2 and 2 (Hour 0 = PGFM peak) of the last PGFM pulse of the preluteolytic period, progesterone decreased between Hours -1 and 0, and then returned to the prepulse concentration. Concentration did not change significantly thereafter until a PGFM pulse early in the luteolytic period; progesterone decreased by Hour 0 and transiently rebounded after Hour 0, but not to the prepulse concentration. In the later portion of the luteolytic period, progesterone also decreased between Hours -1 and 0 but did not rebound. After the defined end of luteolysis, progesterone decreased slightly throughout a PGFM pulse. Results demonstrated for the first time that the patterns of progesterone concentrations within a PGFM pulse differ considerably among the preluteolytic, luteolytic, and postluteolytic periods., (Copyright © 2010 Elsevier Inc. All rights reserved.)

A single physiologic dose (0.1 mg) of estradiol-17beta in sesame-oil vehicle or vehicle alone (n = 8) was given to heifers on day 14 after ovulation to study the effect on circulating 13-14-dihydro-15-keto-PGF2alpha (PGFM), PGFM pulses, and changes in progesterone concentrations within a PGFM pulse. Blood samples were collected hourly for 16 h after treatment. The estradiol group had a greater mean concentration of PGFM, greater number of heifers with PGFM pulses and number of pulses/heifer, and greater prominence of the PGFM pulses. Changes in progesterone concentrations were not detected during the 16 h sampling session in the vehicle group, indicating that the heifers were in preluteolysis. Progesterone decreased after 12 h in the estradiol group, indicating a luteolytic effect of the estradiol-induced PGF secretion as represented by PGFM concentrations. Intrapulse changes in progesterone were detected during a PGFM pulse in the estradiol group (P < 0.006), but not in the vehicle group. Progesterone increased (P < 0.01) between Hours -2 and -1 of an estradiol-induced PGFM pulse (Hour 0 = peak of pulse), decreased (P < 0.004) between Hours -1 and 0, and increased (P < 0.01) or rebounded between Hours 0 and 1. Results were compatible with previous reports of a role for estradiol in the induction of PGFM pulses in cattle and demonstrated intrapulse changes in progesterone concentrations during an induced PGFM pulse., (Copyright 2010 Elsevier Inc. All rights reserved.)

The effects of prostaglandin F(2alpha) (PGF) on circulating progesterone concentration were studied in four groups (n=4) of Holstein heifers 9d after ovulation. The progesterone response to simulation of a pulse of 13,14-dihydro-15-keto-PGF (PGFM) by a 2-h intrauterine (IU) infusion of 0.5mg of PGF was compared with the response to a PGF-bolus IU injection of 4mg. The beginning of infusion and time of injection were designated Minute 0. Progesterone concentration did not change significantly between Minute 0 and Hour 48 in control or IU vehicle-treated groups. In the PGF-bolus group, progesterone concentration increased (P<0.05) between Minutes 0 and 10 and then decreased. In the PGF-infusion group, simulation of a PGFM pulse was not associated with an initial transient increase in progesterone. The first significant decrease (P<0.05) in progesterone began at Minute 20 and continued until Hour 1. The progesterone concentration then began to rebound (P<0.05) at Hour 1 and peaked at Hour 3 at almost the same concentration as at the start of PGF infusion. The progesterone again decreased after Hour 3 and increased again between Hours 24 and 48. In summary: (1) an initial transient increase in progesterone was not detected in association with an individual simulated pulse of PGF, indicating that the frequently reported pronounced transient increase after a bolus luteolytic dose of PGF is a nonphysiological response and (2) simulation of a PGFM pulse resulted in a distinct transient rebound in progesterone beginning at Hour 1 of the PGF infusion., (Copyright 2009 Elsevier B.V. All rights reserved.)

Progesterone and luteal blood flow effects of an i.u. 2-h infusion of 0.25 mg/h of prostaglandin F(2)(alpha) (PGF) that simulated a natural pulse of 13,14-dihydro-15-keto-PGF (PGFM) were compared to the effects of a single bolus i.u. injection of PGF (4 mg) that induced complete luteolysis in heifers. Blood sampling and an estimate of the percentage of luteal area with colour-Doppler signals of blood flow were performed every 2 min for 20 min and less frequently thereafter for 6 h. After the beginning of PGF infusion or a bolus injection, progesterone increased to a peak at 14 and 10 min respectively, and was accompanied by an increase in blood flow in the bolus group but not in the infusion group. Progesterone then decreased for 1 or 2 h and was accompanied by a continued elevation in blood flow in the PGF bolus group and by a slight increase in the PGF infusion group. Progesterone then rebounded in both groups, but the rebound was greater in the infusion group. Blood flow decreased during the descending arm of the progesterone rebound. Cortisol and prolactin began to increase 6 min after the bolus PGF injection but did not increase during or after PGF infusion. The increases in cortisol, prolactin and blood flow after a PGF bolus treatment but not during a simulated PGFM pulse indicated that the bolus treatment was pharmacologic, and its use may lead to faulty conclusions on the nature of physiologic luteolysis. The comparisons between progesterone and blood flow are novel.