Effect of oxytocin on plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha during the oestrous cycle and early pregnancy in the goat.

The effect of subcutaneous oxytocin on plasma concentrations of 13,14-dihydro-15-keto-prostaglandin (PG) F2 alpha (PGFM) was examined in the goat at various periods during the oestrous cycle and early pregnancy. 100 i.u. oxytocin was administered daily for 4 day, the dose being divided and given at 0900 and 2100 h; PGFM concentrations were assessed after the first treatment of each day. On days 3-6 (oestrus, day 0) PGFM concentrations increased significantly (P less than 0.001) within 15 minutes and both non-pregnant and mated goats exhibited oestrus behaviour by day 7. Significant (P less than 0.01) increases in PGFM were also produced on days 7-10, in both non-pregnant and pregnant goats, but the responses diminished from day 7 to day 10; only one goat (non-pregnant) came into oestrus. There was a marked difference in response between groups, however, during days 12-15. In non-pregnant goats significant (P less than 0.05) increases in PGFM were detected on days 13-15, but in pregnant animals oxytocin was without effect. Similarly, oxytocin did not increase PGFM concentrations on days 17-20 of pregnancy. However, uterine responsiveness reappeared in pregnant goats with significant (P less than 0.01) increases in PGFM on days 24 and 25.     

Plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F during pregnancy in sheep

A specific and sensitive radioimmunoassay is described for 13,14-dihydro-15-keto-prostaglandin F in ovine plasma. Using this assay it has been shown that, in sheep, jugular venous 13,14-dihydro-15-keto-prostaglandin F concentrations increase at parturition and correlate well with concentrations of prostaglandin F in the utero-ovarian vein. It is suggested that uterine prostaglandin F production under these conditions may be assessed by measuring peripheral venous 13,14-dihydro-15-keto-prostaglandin F, thereby avoiding the need for chronic utero-ovarian venous catheters.     

Amniotic fluid concentrations of prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11, 16-cyclo-prostaglandin E2 (PGEM-LL) in preterm labor

Although prostaglandins (PGs) are considered the key mediators of human parturition at term, there is a paucity of data regarding their participation in the mechanisms responsible for preterm labor. The purpose of this study was to establish if preterm labor is associated with changes in the amniotic fluid concentrations of prostaglandins. PGF2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-prostaglandin E2 (PGEM-ll) were measured by using specific and sensitive radioimmunoassays. Amniotic fluid was retrieved by transabdominal amniocentesis from 55 women with preterm labor and intact membranes. Patients were divided into three groups according to the response to tocolysis and the presence or absence of an intra-amniotic infection. Amniotic fluid concentrations of PGFM and PGEM-ll were significantly greater in women with preterm labor and intra-amniotic infection than in women without infection. In addition, patients unresponsive to tocolysis without intra-amniotic infection also had a significantly greater concentration of PGFM and PGEM-ll in amniotic fluid than those responsive to tocolysis. Amniotic fluid concentrations of PGF2 alpha were greater in women with intra-amniotic infection than in women without intra-amniotic infection. In the absence of intra-amniotic infection, no difference in amniotic fluid PGF2 alpha concentrations could be found between women who responded to tocolytic treatment and those who did not.     

Jugular levels of 13,14-dihydro-15-keto-prostaglandin F and progesterone around luteolysis and early pregnancy in the ewe

Six non-pregnant ewes at day 12 of the estrous cycle each had a day-12 embryo transferred into the uterine horn ipsilateral to the corpus luteum, and 4 non-pregnant ewes at day 13 each had a day-13 embryo similarly transferred. Four control ewes, 2 at day 12 and 2 at day 13 received sheep serum into the uterine horn ipsilateral to the corpus luteum. Jugular blood samples were taken at 2-hourly intervals for 3 days post-surgery, then twice-daily for a further 4 days, and the plasma radioimmunoassayed for progesterone and 13,14-dihydro-15-keto-prostaglandin F. All control ewes exhibited estrus within the expected time range and pulsatile peaks of 13,14-dihydro-15-keto-prostaglandin F occurred coincident with declining progesterone levels. With one exception, the recipient ewes had prolonged cycles and those ewes found pregnant at necropsy, 30 days after transfer, showed no progesterone decline and no pulsatile peaks of prostaglandin during days 12 to 16 after estrus. These observations suggest that the presence of the embryo at a critical stage after mating suppresses the release of uterine prostaglandin F_2α.     

Temporal relationship between plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F and neurophysin I/II around luteolysis in sheep

Plasma concentrations of neurophysin I/II (N-I/II), 13,14-dihydro-15-keto-prostaglandin F (PGFM) and progesterone were measured by radioimmunoassay in plasma samples collected from four sheep at hourly intervals between 0700 and 1900 h from Days 12–17 of the estrous cycle. Plasma samples were also collected from a fifth sheep at 2-hourly intervals during Days 12–16 of the cycle. In all sheep, intermittent surges in the plasma concentrations of PGFM and N-I/II occurred during the period of luteal regression. On at least one occasion in each sheep a surge in the plasma concentration of N-I/II was observed coincident with a rise in PGFM concentrations. In general, the highest levels of N-I/II were observed early in luteolysis (Days 13–14 of the cycle) while the corresponding levels of PGFM in plasma were maximal around Day 15 when luteolysis was well advanced.It is suggested from this temporal data that oxytocin, which is considered to be released in association with N-I/II, may play an important role in ovine luteolysis by stimulating the secretion of prostaglandin F from the uterus during Days 13–15 of the estrous cycle.     

A quantitative solid-phase enzymeimmunoassay for 13,14-dihydro-15-keto- prostaglandin F2 alpha in plasma.

Enzymeimmunoassays (EIA) can be viable alternatives to radioimmunoassays (RIA). Indeed, from an environmental perspective, EIA are preferable to RIA. Therefore, the purpose of this project was to develop a quantitative EIA for 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) in bovine plasma. Acetylcholine esterase bound covalently to PGFM, rabbit anti-PGFM, mouse monoclonal anti-rabbit IgG, and PGFM were the principle reagents used for the EIA. Validation experiments indicated that: 1) PGFM standard curves, with doses ranging from 391 to 200,000 fg per microtiter well, were linear; 2) assay sensitivity averaged 391 fg per well; 3) for satisfactory results, PGFM had to be extracted from plasma; 4) content of PGFM in ethyl ether extracts of aliquots from serial dilutions of whole plasma with unknown amounts of PGFM and charcoal-stripped plasma supplemented with known amounts of PGFM did not deviate from parallelism with PGFM standard curves in buffer; 5) correlation between EIA and RIA measurements of PGFM in the same plasma samples was .95; 6) the regression of EIA data on RIA data was linear (Y = .93 x + 83.9; r2 = .91); 7) intra- and interassay coefficients of variation were 3.3 and 10.6%, respectively. The EIA developed in this project is a valid and reliable method for quantitating PGFM in extracts of bovine plasma.     

Conditions of the cervix for the increase of plasma levels of 13,14-dihydro-15-keto-prostaglandin F2 alpha after amniotomy at term

Amniotomy was performed in 12 multiparas at term but not in labor. In 6 of these patients (group I), the fetal head and cervix condition were favorable for amniotomy, and in the other 6 (group II), they were not favorable. In all group I patients, a sudden and progressive descent of the fetal head, and onset and progress of labor were noted within 5 hours. Plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) levels increased significantly (P less than 0.05) in 4 of these cases with time. In group II patients, descent of the head was less than that in group I patients (P less than 0.05), and neither strong labor nor rise of PGFM levels was noted within 5 hours. These data support our view that amniotomy at an appropriate time results in the onset and progress of labor, and the rise of plasma PGFM in virtue of the sudden and exponential increase of the head to cervix force, but amniotomy at an inappropriate time does not, because this force is unchanged.     

Radioimmunoassay of 13, 14-dihydro-15-keto-prostaglandin F2alpha

A simple method is described for the determination of 13, 14-dihydro-15-keto-prostaglandin F2alpha (PGFM), using a highly specific antiserum raised in New Zealand rabbits. It involves extraction of human peripheral venous plasma with diethyl ether after addition of tritiated PGFM and HCl. Radioimmunoassay is performed on appropriate aliquots; after 2 hours or overnight equilibration the bound and free metabolite are separated using dextran-coated charcoal. The mean values +/- S.D. obtained are as follows: healthy males 32 +/- 16 pg/ml, females during follicular phase 48 +/- 18 pg/ml, luteal phase 37 +/- 8 pg/ml, first trimester of pregnancy 66 +/- 33 pg/ml, second trimester 67 +/- 42 pg/ml and third trimester 72 +/- 26 pg/ml.     

Elevated concentrations of 13,14-dihydro-15-keto-prostaglandin F-2 alpha in maternal plasma during prepartum luteolysis and parturition in dogs (Canis familiaris)

Concentrations of progesterone and of 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured in plasma collected from 6 bitches every 3 h starting 2.8-4.6 days before parturition (birth of first pup) and continuing until 0.4-0.8 days post partum, and in additional samples collected less frequently. Progesterone concentrations at 48, 24, 12 and 3 h pre partum averaged 2.8 +/- 0.3, 2.2 +/- 0.4, 1.0 +/- 0.3 and 0.7 +/- 0.2 ng/ml. At those times PGFM values averaged 380 +/- 80, 800 +/- 220, 1450 +/- 450 and 1930 +/- 580 pg/ml, respectively. Mean concentrations of PGFM increased about 2.5-fold between 48 and 15 h pre partum in association with the onset of luteolysis, and then increased another 2.5 times before parturition as progesterone fell to nadir values. Peak levels of PGFM ranged from 1060 to 7150 pg/ml (2100 +/- 600 pg/ml) and occurred within 1-9 h after the birth of the first pup and before the birth of the last pup. These results suggest that prepartum luteolysis in dogs is initiated by increases in maternal concentrations of PGF, and that progesterone withdrawal causes a further increase in PGF which completes luteolysis and provides a major portion of the uterotonic activity causing expulsion of pups.     

Evidence that platelet-activating factor suppresses uterine oxytocin-induced 13,14-dihydro-15-keto-prostaglandin F2 alpha release and phosphatidylinositol hydrolysis in the ewe.

This study was conducted to determine whether platelet-activating factor (PAF) (1) attenuated oxytocin-induced secretion of the prostaglandin (PG) F2 alpha metabolite, PGFM, by the ovine uterus in situ and (2) inhibited the generation of the inositol phosphate secondary messengers by endometrial tissue in response to oxytocin challenge in vitro. Ovariectomized ewes received steroid replacement to mimic the luteal phase. Six ewes received intrauterine injections of 200 micrograms PAF/uterine horn/day on Days 11-15, and 6 ewes were treated with vehicle. All ewes received 1 microgram oxytocin i.v. on Days 13-16. Pretreatment of ewes with PAF significantly suppressed PGFM release in response to oxytocin on Days 14 and 15 (p less than 0.005) compared to vehicle-treated ewes. PAF was not administered on Day 16, and the PGFM response to oxytocin was not different between groups. In a second experiment, ewes were given intrauterine injections of 200 micrograms PAF/uterine horn/day (n = 8) or vehicle (n = 7) on Days 11-15, and all ewes received 1 microgram oxytocin i.v. on Days 13 and 14. On Day 15 the uterus was removed, and the incorporation of 3H-inositol into inositol phosphates was determined in caruncular endometrium. Treatment of ewes with PAF in vivo reduced inositol monophosphate (IP1) generated by oxytocin (10(-6) M) by 56.4%, compared to that in endometrium from vehicle-treated controls, and also inhibited the incorporation of 3H-inositol into glycerophosphoinositol (GPI). If PAF was added to the endometrium during the incubation in vitro, the attenuation of inositol phosphate generation did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum luteinizing hormone, 13,14-dihydro-15-keto-prostaglandin F2alpha and cortisol profiles during postpartum anestrus in Brahman and Angus cows

Pluriparous suckled Brahman and Angus cows were utilized to evaluate the effect of breed, day after calving and endogenous opioid peptides (EOP) on hormonal profiles during postpartum anestrus. On Days 17 and 34 after calving, blood samples with and without heparin were collected at 15- and 30-min intervals, respectively, for a 7-h period via jugular cannula. Two hours after the start of blood sampling, cows of each breed were administered either 1 mg/kg iv naloxone or saline. Three hours later, all animals received 10 ng/kg iv GnRH. On Day 34 after calving cows received 0.2 IU/kg iv ACTH. Mean LH, basal LH and area under the LH curve increased (P < 0.01) from Day 17 to Day 34 after calving. Height of LH pulses increased (P < 0.05) by Day 34 after calving. Brahman cows had higher (P < 0.05) mean LH, basal LH, LH pulse frequency and area under the LH curve than Angus cows. Naloxone increased postchallenge area under the LH curve in treated cows above that of control cows (P < 0.06). Naloxone also increased the postchallenge area under the LH curve above that of the prechallenge level (P < 0.01). No breed differences in the response to the naloxone challenge were observed. The LH response to naloxone challenge occurred earlier on Day 34 than on Day 17 after calving but the amount of LH released was similar between days. The GnRH-induced LH release was greater in Brahman than in Angus cows (P < 0.04). Mean cortisol concentrations and area under the cortisol curve decreased (P < 0.05) between Day 17 and Day 34 after calving. Mean cortisol concentrations and area under the cortisol curve were lower (P < 0.01) in Brahman than in Angus cows. Cortisol secretion after ACTH treatment was similar between Brahman and Angus cows. The cortisol response after ACTH challenge was positively correlated (r=0.68; P < 0.001) to the prechallenge area under the cortisol curve. Under optimal environmental conditions Brahman cows have a greater LH release and their anterior hypophysis is more sensitive to GnRH challenge than the Angus cows.     

Development of enzyme immunoassay for serum 13,14-dihydro-15-ketoprostaglandin F2 alpha

An enzyme immunoassay was developed for a convenient and sensitive assay of 13,14-dihydro-15-ketoprostaglandin F2 alpha, a metabolite of prostaglandin F2 alpha appearing in human blood. The compound was chemically conjugated to beta-galactosidase from Escherichia coli. The enzyme-labeled antigen was mixed with a sample containing 13,14-dihydro-15-ketoprostaglandin F2 alpha, and the mixture was allowed to react competitively with the antibody immobilized in a polystyrene tube. The activity of beta-galactosidase bound to the antibody was assayed by fluorometry. The enzyme activity was plotted against the amount of authentic 13,14-dihydro-15-ketoprostaglandin F2 alpha to obtain a calibration curve, and the compound was detectable over a range of 10 fmol to 10 pmol. Prostaglandins were extracted from human serum by the use of an octadecylsilyl silica column, and the extract gave an abnormally high level of 13,14-dihydro-15-ketoprostaglandin F2 alpha by enzyme immunoassay due to the presence of unidentified interfering substance(s), which was removed by high-performance liquid chromatography (HPLC). The purified material gave a value in the order of 0.1 pmol per ml of human serum. Validity of the enzyme immunoassay was confirmed by radioimmunoassay and gas chromatography/mass spectrometry (GC-MS) of a methyl ester n-butoximedimethylisopropylsilyl ether derivative.     

Role of luteinizing hormone in changes in concentrations of progesterone and luteal blood flow during the hours of a simulated pulse of 13,14-dihydro-15-keto-prostaglandin F(2alpha) (PGFM) in heifers

A bolus treatment (e.g., 25 mg) of prostaglandin F(2alpha) (PGF) in the study of luteolysis in cattle results in dubious interpretations. Therefore, in experiment 1 of the present study, a 13,14-dihydro-15-keto-PGF (PGFM) pulse was simulated by incremental intrauterine (IU) infusion of PGF for 2.7 h on Day 14 postovulation. Concentrations of PGFM during the first hour of infusion and at the maximum were not different between simulated (n = 7) and spontaneous (n = 7) pulses. In experiment 2, four groups (n = 6 per group) were treated at Minute 0 (beginning of infusion) as follows: saline (infused IU), PGF (infused IU), acyline/saline, and acyline/PGF. Two hours before Minute 0, each heifer was given flunixin meglumine to inhibit endogenous PGF secretion, and heifers in the acyline/saline and acyline/PGF groups were given acyline to inhibit luteinizing hormone (LH). Plasma progesterone concentrations were similar among groups during Minutes 0 to 60, with no indication of an initial transient progesterone increase in the two PGF groups. Progesterone began to decrease in the PGF groups at Minute 60 and to rebound at Minute 135 after the PGFM peak at Minute 120. The rebound was complete in association with an increase in LH in the PGF group, but it was not complete when LH was inhibited in the acyline/PGF group. Luteal blood flow increased during PGF infusion in the two PGF groups and remained elevated for approximately 2 h after the PGFM peak in the PGF group but not in the acyline/PGF group. Novel findings were that an initial transient increase in progesterone did not occur with the simulated PGFM pulse and that LH stimulated a progesterone rebound and maintained the elevated luteal blood flow after the PGFM peak.     

Plasma levels of progesterone, provera, oestradiol-17beta, and 13,14-dihydro-15-keto-prostaglandin F in cows treated with provera-impregnated intravaginal sponges.

Plasma concentrations of progesterone and Provera were measured daily in 3 cows during 21 days of treatment with Provera-impregnated intravaginal sponges. Plasma concentrations of oestradiol-17beta and 13,14-dihydro-15-keto-prostaglandin F (PGFM) were measured hourly from 5 h before until 62 h after sponge removal. The profile of progesterone concentrations indicated that luteolysis occurred at the expected time (Days 19 to 23 of the cycle), even though plasma Provera concentrations were 150-250 pg/ml. The occurrence of peaks of PGFM after sponge withdrawal suggests that PGF-2alpha release is stimulated by falling levels of progestagen.     

Radioimmunoassay of 13,14-dihydro-15-keto prostaglandin F in bovine peripheral plasma

A radioimmunoassay has been developed for 13,14-dihydro-15-keto-prostaglandin F in bovine peripheral plasma. Acidified plasma samples were extracted with diethyl ether and the dried extracts assayed for 13,14-dihydro-15-keto-prostaglandin F using antiserum raised against a 13,14-dihydro-15-keto-prostaglandin F_2α-albumin complex. The tracer used for the assay was prepared enzymatically from tritiated prostaglandin F_1α. Polyethylene glycol was employed to separate free and bound 13,14-dihydro-15-keto-prostaglandin F. The inter-assay coefficient of variation based on 9 determinations of control plasma was 13.8%. The detection limit of the assay was 25 pg 13,14-dihydro-15-keto-prostaglandin F/ml plasma.In 3 cows around estrus there was a complex series of peaks of 13,14-dihydro-15-keto-prostaglandin F concentrations coincident with luteolysis and declining progesterone concentrations. Changes in peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F in the pregnant cow near term showed a close correlation with prostaglandin F levels in utero-ovarian venous plasma. The concentration of 13,14-dihydro-15-keto-prostaglandin F in 12 men was 114±20 pg/ml plasma. It is concluded that the measurement of peripheral 13,14-dihydro-15-keto-prostaglandin F concentrations may offer a simple and convenient method for monitoring uterine prostaglandin F production in the cow.     

Radioimmunoassay of 13,14-dihydro-15-keto prostaglandin F in bovine peripheral plasma

A radioimmunoassay has been developed for 13,14-dihydro-15-keto-prostaglandin F in bovine peripheral plasma. Acidified plasma samples were extracted with diethyl ether and the dried extracts assayed for 13,14-dihydro-15-keto-prostaglandin F using antiserum raised against a 13,14-dihydro-15-keto-prostaglandin F_2α-albumin complex. The tracer used for the assay was prepared enzymatically from tritiated prostaglandin F_1α. Polyethylene glycol was employed to separate free and bound 13,14-dihydro-15-keto-prostaglandin F. The inter-assay coefficient of variation based on 9 determinations of control plasma was 13.8%. The detection limit of the assay was 25 pg 13,14-dihydro-15-keto-prostaglandin F/ml plasma.In 3 cows around estrus there was a complex series of peaks of 13,14-dihydro-15-keto-prostaglandin F concentrations coincident with luteolysis and declining progesterone concentrations. Changes in peripheral plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F in the pregnant cow near term showed a close correlation with prostaglandin F levels in utero-ovarian venous plasma. The concentration of 13,14-dihydro-15-keto-prostaglandin F in 12 men was 114±20 pg/ml plasma. It is concluded that the measurement of peripheral 13,14-dihydro-15-keto-prostaglandin F concentrations may offer a simple and convenient method for monitoring uterine prostaglandin F production in the cow.     

Effects of dibutyryl cAMP, LHRH, and aromatase inhibitor on simultaneous outputs of prostaglandin F2 alpha, and 13,14-dihydro-15-keto-prostaglandin F2 alpha by term placental explants

Explants from term human placentas were maintained in culture with daily changes of medium. Daily output of PGF2 alpha and PGFM1 decreased during the course of the incubation. Addition of 4 micrograms/ml DHEAS or 67 micrograms/ml LDL cholesterol had no effect on output of PGF2 alpha or PGFM. Addition of 1.6, 3.2, or 6.4 micrograms/ml of LHRH to the culture plates had no effect on output of PGFM or PGF2 alpha, but LHRH increased hCG output. Dibutyryl cAMP (1mM, 2mM, and 4 mM) increased output of PGF2 alpha, PGFM, and hCG. Aromatase inhibitor decreased hCG output, but it was without effect on output of PGF2 alpha, or PGFM, Significant correlations were demonstrated between progesterone, PGFM, PGF2 alpha, and hCG, suggesting that PGF2 alpha originates in the syncytiotrophoblast cell. The ability of LHRH to stimulate output of hCG but not PGF2 alpha while dbcAMP stimulated both suggests that either PGF2 alpha and hCG arise in different cells or that LHRH does not act through cAMP.     

GnRH effects on placental hormones during gestation. III. Prostaglandin E, prostaglandin F, and 13,14-dihydro-15-keto-prostaglandin F

We studied the release of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (MPF) from explants of human placentas of different gestational ages and the effect of gonadotropin-releasing hormone (GnRH) on this release. The greatest basal release of PGE, PGF and MPF was in the cultures from 9- to 13-wk placentas, with the release on the second and third days of culture increasing 4- to 10-fold from that of the first day. In cultures from 15-wk to term placentas, the initial basal release (Day 1) of these prostaglandins was only slightly higher than in cultures from 6-wk placentas. In cultures from term placentas, the later increase with extended culture was absent or very small. Addition of synthetic GnRH to the cultures from 6- to 9-wk placentas effected no significant change in release of PGE, PGF or MPF. However, GnRH added to the cultures from 13-wk placentas effected a dose-related inhibition of these prostaglandins. After 15 wk, we observed a stimulation of these prostaglandins by GnRH that was as much as 50-fold; stimulation was highly significant in the cultures from 16- and 17-wk, as well as in those from the term placentas. These data demonstrate an action of GnRH on prostaglandin release and indicate that both the basal release of PGE, PGF and MPF and the response to GnRH are related to the gestational age of the placenta.     

Plasma concentrations of progesterone and 13,14-dihydro-15-keto-prostaglandin F-2 alpha during regression of the corpora lutea of lactation in the bandicoot (Isoodon macrourus)

Plasma progesterone concentrations (mean +/- s.e.m.) declined from 7.5 +/- 1.2 ng/ml and 7.5 +/- 1.0 ng/ml to less than 1 ng/ml after removal of pouch young (RPY) from bandicoots at Days 24 and 30 of lactation respectively. In all 7 bandicoots, the corpora lutea of lactation showed signs of regression and, in 5 of these bandicoots, a premature ovulation had occurred 6-9 days after RPY. There was no change in the concentration of PGFM after RPY, and uterine prostaglandin F-2 alpha may not be involved in luteal regression in the bandicoot.     

Concentrations of 13, 14-dihydro-15-keto-prostaglandin F(2)alpha, estradiol-17beta and progesterone during the peripubertal period in heifers

Twenty prepubertal Holstein heifers were utilized to assess plasma 13, 14-dihydro-15-keto-prostaglandin F(2)alpha (PGFM), serum progesterone (P(4)) and estradiol-17beta (E(2)) concentrations as well as the E(2):P(4) ratio during the onset of puberty in cattle. All animals were maintained as a group along with a sterile marker bull to assist in the detection of estrus. Upon detection of the first estrus (Day=O), daily blood samples were collected from a jugular vein until the heifers had completed 3 estrous cycles. The average body weight and age at first estrus were 247.6+/-4.8 kg and 304.0+/-7.5 days, respectively. Frequency of abnormal length estrous cycles was greater (P<0.02) during the first (40%) and second (35%) cycles than during the third estrous cycle (0%). All heifers had normal cycle lengths (18 to 24 days) by the third estrous cycle. Serum P(4) was greater during the third cycle (P<0.05) from Day 10 to Day 4 before the next estrus compared with the same period of the first estrous cycle. Serum E(2) did not peak until the day of estrus in the first cycle, whereas E(2) reached a maximal level 2 days before estrus in the third estrous cycle. Serum E(2) was higher (P<0.0001) 2 days before estrus in the third cycle than in the first estrous cycle. Plasma PGFM reached maximum concentrations 3 days before estrus in the third cycle compared with 1 day before estrus at the end of first estrous cycle. As estrus approached during the third cycle, PGFM rose 1 day before E(2) rose and P(4) declined, while the rise in PGFM and E(2) occurred simultaneously, with P(4) declining at the end of the first estrous cycle. During diestrus, the E(2):P(4) ratio was lower (P<0.07) in the third cycle than in the first, but it was higher (P<0.04) at estrus and 1 day before in the third estrous cycle. These data reveal a high incidence of abnormal length estrous cycles during the first two estrous cycles of the peripubertal period, and demonstrate anomalies in uterine and ovarian endocrine activity during the peripubertal period in cattle.