The effects on stretching and prostaglandin F2alpha on the contractile and bioelectric activity of the uterus in rat.

The effects of stretching and of prostaglandin F2alpha on spontaneous and induced with local deformation contractile activity of rat uterus were studied. It was found that stretching the uterus up to the length of the decontracted organ in vivo increased the contractile and bioelectric activity. The rise in spontaneous uterine activity was a factor reducing induction of additional contractions. The fall in the level of endogenous prostaglandins in the uterus following administration of indomethacin inhibited the spontaneous contractile activity but was without effect on the contractions induced by local deformation of the myometrium. Prostaglandin F2alpha added to the bath in a concentration of 0.001 ng/ml exerted an inhibitory action on the different tested parameters of the contractile activity. After high doses stimulation of the uterine activity was observed.     

Effect of prostaglandin F2alpha dosage and stage of estrous cycle on the estrous response and corpus luteum function in beef heifers

Ninety-five normal cyclic crossbred beef heifers were used to determine if the proportions of heifers showing estrus, intervals to estrus and corpus luteum (CL) function were influenced by PGF(2alpha) dosage and (or) the stage of luteal phase when PGF(2alpha) was administered. Heifers were assigned randomly to treatments in a 4 x 3 factorial arrangement. Treatments were 5, 10, 25 or 30 mg PGF(2alpha) injected either in early (5 to 9 d), mid (10 to 14 d) or late (15 to 19 d) stages of the luteal phase. Jugular samples were taken at 0 h and at 8 h-intervals for 48 h and again at 60 h after PGF(2alpha) treatment for progesterone assay. Heifers were observed for estrus continuously for 120 h PGF(2alpha) treatment. The proportion of heifers showing estrus was dependent upon (P<0.05) both dosage of PGF(2alpha) and stage of luteal phase. Heifers given 5 mg of PGF(2alpha) showed estrus only if treated during the late stage, while those given 10 mg of PGF(2alpha) showed a progressive increase of heifers in estrus as stage of luteal phase advanced. The proportion of heifers showing estrus after 25 and 30 mg of PGF(2alpha) increased from 56% for the early stage to 100% for the mid and late stages. Interval to estrus in heifers showing estrus within 120 h after PGF(2alpha) treatment did not differ (P>0.05) among dosages but tended (P=0.10) to be longer in heifers treated during the mid luteal stage (67 h) than in heifers treated in the two other stages (56 h). A greater proportion of heifers (P<0.05) showed estrus by 60 h after PGF(2alpha) when treated during the early and late luteal stages (75.5%) than for heifers treated during the mid luteal stage (30.4%). Patterns of progesterone concentrations were influenced (P=0.08) by the three way interaction of dosage, stage and time. In heifers that showed estrus, rate of decline in progesterone tended (P=0.07) to be slower during the mid luteal stage than during the early and late stages. Progesterone did not drop below 1 ng/ml until 32 h in heifers treated during the mid luteal stage; whereas progesterone dropped below 1 ng/ml by 24 h in heifers treated during the early and late stages. These data may be useful in designing more efficient systems for using PGF(2alpha) or its analogues in estrus synchronization of beef cattle.     

Uterine secretion of prostaglandin F2 alpha in response to oxytocin in ewes: changes during the estrous cycle and early pregnancy.

Experiment 1 was conducted to determine when the ovine uterus develops the ability to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin and how development is affected by pregnancy. Pregnant and nonpregnant ewes received an injection of oxytocin (10 IU, i.v.) on Day 10, 13, or 16 postestrus. Jugular venous blood samples were collected for 2 h after injection for quantification of 13,14-dihydro-15-keto-PGF2 alpha (PGFM). In nonpregnant ewes, concentrations of PGFM increased following oxytocin on Day 16 but not on Day 10 or 13. Concentrations of PGFM did not increase following treatment on Day 10, 13, or 16 in pregnant ewes. Therefore, the ability of oxytocin to induce uterine secretion of PGF2 alpha develops after Day 13 in nonpregnant but not in pregnant ewes. Experiment 2 was conducted to precisely define when uterine secretory responsiveness to oxytocin develops. Pregnant and nonpregnant ewes received oxytocin on Day 12, 13, 14, or 15. In nonpregnant ewes, concentrations of PGFM increased following treatment on Days 14 and 15, but not earlier. Peripheral concentrations of progesterone showed that uterine secretory responsiveness to oxytocin developed prior to the onset of luteal regression. As in experiment 1, the increase in concentrations of PGFM following administration of oxytocin was much lower in pregnant than in nonpregnant ewes; however, some pregnant ewes did respond to oxytocin with an increase in PGFM. In experiment 3, pregnant ewes received an injection of oxytocin on Day 18, 24, or 30 postmating. Concentrations of PGFM increased following oxytocin on Days 18 and 24. The conceptus appears to delay and attenuate the development of uterine secretory responsiveness to oxytocin.     

Changes in uterine secretion of prostaglandin F2 alpha and luteal secretion of progesterone in response to oxytocin during the porcine estrous cycle.

The purpose of this experiment was to determine whether the ability of oxytocin to stimulate uterine secretion of prostaglandin F2 alpha (PGF2 alpha) and luteal secretion of progesterone changes during the porcine estrous cycle. Nineteen multiparous sows were observed for estrus. After one estrous cycle of normal length, sows were assigned randomly to receive an injection of oxytocin (30 IU, i.v.) in the EARLY (Days 4-6; n = 6), MID (Days 9-11; n = 7), or LATE (Day 15; n = 6) stage of the estrous cycle. Concentrations of 13, 14-dihydro-15-keto-PGF2 alpha (PGFM) and progesterone were determined in jugular venous serum samples collected at -60, -45, -30, -15, 0, 2, 5, 10, 15, 30, 45, 60, 90, and 120 min after injection of oxytocin. The magnitudes of the PGFM and progesterone responses and the area under the respective response curves (AUC) were calculated for each sow. Concentrations of PGFM did not change in response to oxytocin administered during the EARLY or MID portions of the estrous cycle. Concentrations increased rapidly in 4 of 6 sows that received oxytocin LATE in the estrous cycle. Both magnitude and AUC were greater LATE in the estrous cycle than at either EARLY or MID cycle (p less than 0.05). Thus, uterine secretory responsiveness to oxytocin develops between Days 11 and 15 postestrus in the sow. For progesterone, a transient increase was observed immediately following injection of oxytocin at MID cycle (p less than 0.05), but not at the other times examined. Therefore, oxytocin appears to be capable of stimulating secretion of progesterone from the functionally mature corpus luteum.     

Prostacyclin, prostaglandin F2 alpha and progesterone production by bovine luteal cells during the estrous cycle

Corpora lutea (CL) were collected from Holstein heifers on Days 5, 10, 15 and 18 (5/day) of the estrous cycle. Dispersed luteal cell preparations were made and 10(6) viable luteal cells were incubated with bovine luteinizing hormone (LH) and different amounts of arachidonic acid in the presence and absence of the prostaglandin (PG) synthetase inhibitor indomethacin. The concentrations of progesterone, PGF2 alpha and 6-keto-PGF1 alpha, the stable inactive metabolite of prostacyclin (PGI2), were measured. Day 5 CL had the greatest initial content of 6-keto-PGF1 alpha (1.01 +/- 0.16 ng/10(6) cells), and synthesized more 6-keto-PGF1 alpha (2.55 +/- 0.43) than CL collected on Days 10 (0.57 +/- 0.11), 15 (0.08 +/- 0.05) and 18 (0.19 +/- 0.03) during a 2-h incubation period. Arachidonic acid stimulated the production of 6-keto-PGF1 alpha by Days 10, 15 and 18 luteal tissue. PGF2 alpha was produced at a greater rate on Day 5 (0.69 +/- 0.17 ng/10(6) cells) than on Days 10 (0.06 +/- 0.01), 15 (0.04 +/- 0.02) and 18 (0.08 +/- 0.01). Arachidonic acid stimulated and indomethacin inhibited the production of PGF2 alpha, in most cases. The initial content of 6-keto-PGF1 alpha was higher than that of PGF2 alpha on all days of the cycle and more 6-keto-PGF1 alpha was synthesized in response to arachidonic acid addition. The ratio of 6-keto-PGF1 alpha content to PGF2 alpha content was 4.39, 2.30, 1.25 and 1.13 on Days 5, 10, 15 and 18, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of prostaglandin F2alpha on the activator calcium of the uterus.

The mechanism through which PGF2_α exerts its oxytocic action was studied in 150 uterine strips, 48 excised from 25 days pregnant and 102 from post partum rabbits. PGF2_α delayed the loss of excitability upon exposure of the uterus to Ca-free Krebs Ringer Bicarbonate (KRB) solution and accelerated recovery when half (1.25 mM) of the normal CaCl₂ was replaced in the KRB. This effect of PGF2_α was more pronounced in the post partum than the pregnant uterus, which resisted Ca-deficiency by high affinity binding in its plasma membrane of the activator-Ca (A-Ca).The Ca-ionophore A23187 simulated the action of PGF2_α but only during stimulation with 12 V/5 cm and not with 60 V/5 cm. This finding suggests that while the effect of PGF2_α is limited to a control of the movement of the extracellular and membrane-bound Ca, A23187 affects the distribution of Ca liberated by the strong (60 V/5 cm) electric field from internal stores of the myometrial cells. In the presence of Ruthenium-red (a Ca-influx inhibitor) and only 1.25 mM CaCl₂, PGF2_α restored excitability slowly, indicating that PGF2_α is an oxytocic agent because it promotes Ca-influx. However, knowing that Ca-efflux is in part dependent upon Ca-influx the most informative present finding was the observation that PGF2_α did not promote ⁴⁵Ca-efflux when ⁴⁰Ca-influx was inhibited by Verapamil. This demonstration provided more direct evidence that PGF2_α promotes the influx of the A-Ca and thus explained the mechanism of action of this key regulator at the molecular level.     

Histophysiological studies of prostaglandin F2alpha on isolated organs. I. Effect of prostaglandin F2alpha on the heart.

The physiological and histochemical effects of PGF2alpha on isolated rabbit hearts were examined. The results showed a positive inotropic effect. The coronary flow increased. From the histochemical studies, adenosine triphosphatase (ATP-ase) and succinic dehydrogenase activities were increased while that of alkaline phosphatase was decreased. Glycogen granules were depleted. These findings were discussed on a histophysiological basis.     

Influence of prostaglandin F autoantibodies on the estrous cycle of the guinea pig.

Adult female guinea pigs were actively immunized with prostaglandin F-2alpha conjugated to bovine serum albumin (BSA). Control animals, immunized against BSA continued to cycle normally, while the animals immunized against prostaglandin F-2alpha stopped cycling after one to three normal cycles. Laparotomy at 30 days after the last estrus revealed no recently formed corpora lutea. During the remaining 70 days of observation the antibody titer increased to 1:700, accompanied by increasing total serum estrogens (136 pg/ml at day 100) and a slow decline in circulating progesterone levels (0.6 ng/ml at day 100). The ovaries at day 100 contained degenerated corpora lutea and luteinized follicles. The suppression of the estrous cycle in the present experiments was interpreted as resulting from prolongation of luteal function as well as from inhibition of ovulation.     

Biosynthesis and catabolism of prostaglandin F2alpha (PGF2alpha) are controlled by progesterone in the rat uterus during pregnancy

Myometrial quiescence is a key factor in all species to accomplish a successful gestation. PGs play a crucial role in mediating parturition events, and their synthesis and metabolism are regulated by cyclooxygenases (COXs) and NAD(+)-dependent 15-hydroxy-PG dehydrogenase (PGDH), respectively. Progesterone (P(4)) is the hormone responsible for maintaining uterine smooth muscle quiescence during pregnancy. In this work, we have studied the effect of P(4) on the activity of COXs and PGDH, the uterine enzymes involved in the biosynthesis and metabolism of prostanoids in the rat. We found that during pregnancy PGF(2alpha) production and also protein levels of COX-1 and COX-2 were decreased. The exogenous administration of P(4) significantly inhibited the uterine production of PGF(2alpha) and also the protein level of COX-2. PGF(2alpha), metabolism was assessed by PGDH activity, which resulted high during pregnancy and increased as a result of P(4) administration. These results indicate that PGs levels were negatively modulated by P(4), which could be exerting its effect by increasing PGs metabolism through stimulation on PGDH activity and an inhibition on COX and that is a major mechanism for maintain uterine quiescence in pregnancy.     

Estrus induction with prostaglandin F2alpha, cloprostenol or fenprostalene during the normal estrous cycle, superovulation and after embryo collection

Holstein heifers used as embryo donors were treated with three luteolytic agents (PGF2alpha, cloprostenol, fenprostalene) during the normal estrous cycle, superovulation or after embryo collection to determine the interval from treatment to estrus. A similar return-to-estrus interval was observed for each luteolytic agent among the three groups of heifers. Nevertheless, after embryo collection, fenprostalene had a tendency to induce the longest delays (p = 0.08). This tendency is supported by a higher proportion of delayed luteolysis and more heifers showing estrus later than 11 d post treatment. Also, during normal estrous cycles, 5/10 and 0/8 fenprostalene- and cloprostenol-treated heifers, respectively, showed progesterone concentrations higher than 1 ng/mL 48 h after treatment. Regardless of the luteolytic agent used, estrus was induced earlier (P < 0.005) during superovulation than when heifers were treated between Days 9 to 16 of the normal estrous cycle or after embryo collection. However, the return-to-estrus interval was similar between heifers treated during superovulation and those treated between Days 6 to 8 of the normal estrous cycle. After embryo collection, intervals before the return to estrus increased with the number of Corpora lutea (CL) palpated except in the nonresponding group (0 to 1 CL), which returned to estrus later than the low responding group (2 to 4 CL).     

Effect of prostaglandin F2alpha on ovarian and pituitary function in the mid-luteal phase.

The effects of PGF2alpha infusion in a dose of 25 micrograms/min for 5 hours on serum levels of estradiol-17beta, progesterone, LH, FSH, TSH and prolactin, and on the pituitary hormone responsiveness to LRH and TRH were studied in 10 apparently healthy cycling women in the mid-luteal phase. No systematic alteration was seen in the pituitary and ovarian hormone levels during PGF2alpha infusion, and the pituitary hormone responses to releasing hormones were unaffected. Ovarian steroid production increased in response to increased gonadotropin levels after LRH injection during PGF2alpha administration. These results confirm that PGF2alpha is not luteolytic in humans and no apparent relationship between PGF2alpha and pituitary hormone secretion exists.