Plasma levels of 13,14-dihydro-15-keto prostaglandin F2α, estrogens, and progesterone during stretch-induced labor at term

The uterus of six healthy multiparous women at term was mechanically stretched by a rubber catheter and balloon. Apparent labor was inaugurated in all cases within 5 hours and increased progressively with time. Advanced cervical softening and dilatation were also evident after the stretch treatment. Significant increases in the levels of 13,14-dihydro-15-keto-prostaglandin F_2α (PGFM) were observed with the progress of treatment (P < 0.01). Plasma estrogens and progesterone levels did not change significantly during the treatment (P > 0.05). Stretching and/or resulting uterine contractions appear to induce the secretion of prostaglandin F_2α (PGF) from the organ, which in turn seems to be involved in both cervical softening, and the onset and progress of labor, under stable conditions of plasma estrogens and progesterone.     

F prostaglandin levels in amniotic fluid during balloon-induced cervical softening and labor at term

Mechanical stretching of the uterus was applied to seven term patients not in labor with unripe cervix by means of intra-uterine application of a rubber balloon. Significant cervical softening, and initiation and progress of labor was achieved in all cases. Serial analyses of the F prostaglandins (PGF) in amniotic fluid were performed before and at given intervals of cervical dilatation. Before the application of stretch, the level of PGF varied greatly; the values in 5 cases were measureable but low (less than 645 pg/ml) and in two cases the levels were below the sensitivity of the assay (less than 50 pg/ml). Large fluctuations of the levels were noted in many cases during the treatment. However, the rise of the PGF values was significantly with the progress of cervical dilatation compared to the pre-treatment values (P<0.05 at both 3–4 and 5–6 cm, and P<0.01 at 9–10 cm). It was concluded that the increased release of PGF in amniotic fluid is mediated by uterine stretching, and that upon being released PGF is probably involved in the cervical softening and progress of labor.     

Fetal viability does not affect the onset of stretch-induced labor and the increase in amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels.

The role of the fetus in the onset and progress of stretch-induced labor and in the change in amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels was evaluated in six normal pregnant women (group 1) and six women whose fetuses had been dead for more than one week (group 2). The uterus was distended by a balloon inflated with physiologic saline. Regular uterine contractions occurred, and increased in all patients. Within 21 hours, all patients delivered a normal baby in group 1 and a macerated fetus in group 2. There was no significant difference in induction-delivery interval between the two groups. Both groups showed a significant and similar range of increases in the levels of amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite during treatment (P less than 0.001). Thus, the fetus has no functional role in the onset and progress of stretch-induced labor or in the rise of amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels.     

Effects of prostaglandins, dibutyryl cAMP, LHRH, estrogens, progesterone, and potassium on output of prostaglandin F2 alpha, 13, 14-dihydro-15-keto-prostaglandin F2 alpha, hCG, estradiol, and progesterone by placental minces

In order to compare the endocrine response of placental minces to luteinizing hormone releasing hormone (LHRH) and dibutyryl cAMP (dbcAMP) and to screen for effects of potential stimulatory and inhibitory substances, the simultaneous outputs of PGF2 alpha, 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), progesterone, 17 beta-estradiol, and hCG were evaluated during a 4 hour incubation in 5 placentas. The output of hCG was highest for 12-week placentas, intermediate for a 16 week placenta, and lowest for term placentas. The output of 17 beta-estradiol by 12 and 16 week placentas in the presence of 30 microM dehydroepian-drosterone sulfate (DHEAS) was greater than that by term placentas. Progesterone output was apparently independent of gestational age although some variation between 12-week placentas was demonstrated. Output of PGF2 alpha was lower in 12 and 16-week placentas than in term placentas and that of PGFM was lower in 12-week placentas than in term placentas. LHRH (100 nM) produced stimulation of PGF2 alpha output (P less than .005) and a trend toward inhibition of progesterone output (which failed to achieve statistical significance) but no stimulation of hCG under these conditions. Stimulation of the outputs of hCG (P less than .005) and PGF2 alpha (P less than .001) and inhibition of that of progesterone (P less than .005) was produced by 20 mM dbcAMP. DHEAS inhibited output of progesterone (P less than .01) and PGF2 alpha (P less than .01). There were no effects of potassium, estrogens, progesterone, or prostaglandins on output of any measured substance.     

Effects of prostaglandins on the bovine corpus luteum: granules, lipid inclusions and progesterone secretion

Corpora lutea collected at 15, 30 and 60 min after prostaglandin F2 alpha (PGF2 alpha) treatment were compared to control corpora lutea at 60 min after saline treatment. There were decreases (P less than 0.05) in the relative percentages of cytoplasm occupied by granules in large luteal cells (LLC) by 30 min and in small luteal cells (SLC) by 60 min. Differences were not observed among the groups for lipid inclusions. Luteal progesterone was decreased at all post-PGF2 alpha treatment times when compared to 60-min controls (P less than 0.05). PGF2 alpha was then compared with prostaglandin F1 alpha (PGF1 alpha), prostaglandin E1 (PGE1), and 17-phenyl-18,19,20-trinor-prostaglandin F2 alpha (17-phenyl-PGF2 alpha) in 60-min trials with plasma progesterone and luteinizing hormone (LH) determined every 5 min. LH was not affected by these treatments. Like PGF2 alpha, 17-phenyl-PGF2 alpha induced a greater loss of granules from LLC then SLC. 17-phenyl-PGF2 alpha also induced an increase in the lipid content of LLC. Treatments with PGF2 alpha and 17-phenyl-PGF2 alpha were associated with decreased concentrations of luteal progesterone but PGF1 alpha and PGE1 were without effect on this variable. In contrast to PGF1 alpha, PGE1 increased both luteal progesterone and the area occupied by cytoplasmic granules. The latter effect was greater in LLC than SLC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergistic effects of antiprogestins and iNOS or aromatase inhibitors on establishment and maintenance of pregnancy

Progesterone is known to be involved in many steps in female reproduction including control of implantation and uterine-cervical function during pregnancy. Our studies in rats and guinea pigs indicate that progesterone inhibits uterine contractility and cervical softening during pregnancy. Progesterone levels or actions decline near the end of pregnancy leading to the onset of labor. Treatment with progestin agonists prolongs pregnancy and inhibits cervical softening, whereas treatment with antiprogestins (mifepristone or onapristone) stimulates uterine contractility, cervical softening and premature delivery. Thus the effect of progesterone receptor modulators in the uterus and cervix depend up on the degree of intrinsic agonistic/antagonistic activities. Our recent studies show that progesterone interacts with nitric oxide (NO) to maintain pregnancy and that administration of progesterone antagonists with NO synthase inhibitors act synergistically to stimulate labor. In addition our studies show that combinations of progesterone antagonists with aromatase inhibitors act synergistically to induce labor. Similarly antiprogestins interact with NO synthase or aromatase inhibitors to block implantation through action on the endometrium. These studies suggest new applications for combined therapies of progestin receptor modulators with aromatase inhibitors or agents that modify NO production for contraception, stimulation of labor, estrogen-dependent diseases and improved outcomes in pregnancy.     

Changes in the plasma prostaglandin F2 alpha metabolite before and during spontaneous labor and labor induced by amniotomy, oxytocin and prostaglandin E2

To elucidate the role of endogenous prostaglandin F2 alpha in spontaneous and induced labor, plasma concentrations of 13, 14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were determined before the onset of labor, at onset of labor, during active labor, at the crowning of the fetal head, and 1 and 2 hours after delivery. Patients in spontaneous labor and labor induced by amniotomy, oxytocin, and prostaglandin E2 were studied. The levels of plasma PGFM in patients who entered spontaneous labor fell 2 to 3 weeks before delivery, whereas those in the induced labor group did not change until the time of induction. Although the levels of PGFM rose gradually with the progress of labor in all cases, the levels in the spontaneous labor were significantly lower in each stage than in the corresponding stage of induced labor. These results suggest that endogenous prostaglandin F2 alpha (PGF2 alpha) production decreases 2-3 weeks prior to the spontaneous onset of labor and is increased again as labor progresses, that the patterns of PGF2 alpha production are similar to each other during spontaneous labor and labor induced by various methods. Therefore, it is felt that endogenous PGF2 alpha may participate in the progress of all kinds of labor.     

Hormonal regulation of PGE2 and COX-2 production in rabbit uterine cervical fibroblasts.

Prostaglandins (PGs) cause uterine contraction to initiate labor at term. We investigated the effect of progesterone and 17beta-estradiol on the production of PGE2 in rabbit uterine cervical fibroblasts. When the cervical fibroblasts were treated with interleukin-1alpha (IL-1alpha), the level of PGE2 was augmented in a time- and dose-dependent manner. The IL-1alpha-augmented PGE2 level was almost completely suppressed by progesterone and 17beta-estradiol at the physiological concentration (0.01 microM), whereas a slight decrease in the basal level of PGE2 was observed in the cervical fibroblasts treated with both hormones at a pharmacological concentration (1 microM). In addition, the level of PGE2 augmented by IL-1alpha was due to the increase of cyclooxygenase (COX) activity, which was inhibited by progesterone and 17beta-estradiol as well as by indomethacin and a specific COX-2 inhibitor, NS-398, but not by the well-known COX-1 inhibitor, aspirin. Furthermore, progesterone and 17beta-estradiol suppressed the IL-1alpha-augmented COX-2 production but not the constitutive production of COX-1 in rabbit uterine cervical fibroblasts. These results suggest that progesterone and 17beta-estradiol prevent the initiation of labor by inhibiting PGE2 production after the suppression of COX-2 production during pregnancy in the rabbit.     

Localization of prostaglandin F2 alpha inhibition of lipoprotein use by bovine luteal cells.

Prostaglandin F2 alpha (PGF2 alpha) inhibits lipoprotein-stimulated progesterone production by bovine luteal cells in vitro and the objective of this study was to localize the site of action of PGF2 alpha. Cultured bovine luteal cells were treated with PGF2 alpha for seven days, and then with either lipoproteins or 25-hydroxycholesterol in the presence of aminoglutethimide (which inhibits cholesterol side-chain cleavage) for the final 48 h. The effects of PGF2 alpha on progesterone production, cellular cholesterol content, mitochondrial cholesterol content and cholesterol side-chain cleavage activity were determined. As expected, PGF2 alpha inhibited (P less than 0.05) lipoprotein-stimulated progesterone production. However, PGF2 alpha did not inhibit low-density lipoprotein-stimulated, or high density lipoprotein-stimulated, increases in cellular cholesterol (P less than 0.05) or inhibit lipoprotein-induced increases in mitochondrial cholesterol content (P less than 0.05). Additionally, cholesterol content of mitochondria increased (P less than 0.05) in the presence of PGF2 alpha alone. To determine if the PGF2 alpha-induced inhibition of steroidogenesis occurred at, or after, the side-chain cleavage reaction, we treated cells with the readily diffusable sterol, 25-hydroxycholesterol. Prostaglandin F2 alpha did not inhibit 25-hydroxycholesterol-stimulated progesterone production (P less than 0.05). Prostaglandin F2 alpha may therefore exert its luteolytic effect at a site after cholesterol transport to the mitochondria but before cholesterol side-chain cleavage.     

Cell-type specific responses in prostaglandin secretion by glandular and stromal cells from pig endometrium treated with catecholestrogens, methoxyestrogens and progesterone.

The pig conceptus and endometrium possess the ability to convert estrogens into catecholestrogens and catecholestrogens into methoxyestrogens. Experiments were carried out to evaluate the effect of catecholestrogens, methoxyestrogens and progesterone on the secretion of prostaglandin (PG) E and F2 alpha by porcine endometrial glandular and stromal cells in vitro. Both 2-hydroxyestradiol (2-OH-E2, 0-20 microM) and 4-hydroxyestradiol (4-OH-E2, 0-20 microM) increased (P less than .05) PGE and PGF2 alpha secretion by stromal cells in a dose response manner. Two-hydroxyestradiol tended (P less than .1) to decrease PGF2 alpha production by glandular cells. Two-methoxyestradiol (20 microM) suppressed (P less than .05) PGF2 alpha secretion by glandular and stromal cells. Four-methoxyestradiol (20 microM) stimulated (P less than .05) PGE production and PGE:PGF2 alpha ratio. Progesterone (.1 microM) suppressed (P less than .05) PG secretion in both cell types. We conclude that catecholestrogens, methoxyestrogens, and progesterone may participate in the establishment of pregnancy by modulating PG production in the endometrium.     

The ovarian and cervical regions of the rat uterus display a different contractile response to serotonin and prostaglandin F2alpha. I. The estrous cycle

In pharmacological studies using isolated tissues, the sensitivity to different agonists may vary depending on the anatomical region. The aim of the present study was to evaluate the in vitro contractile response to serotonin, prostaglandin F2alpha, and oxytocin of the ovarian and the cervical uterine segments isolated from rats in the four different stages of the rat estrous cycle. Non-cumulative curves were recorded for both, the ovarian and the cervical uterine segments. The cervical portion displayed a higher contractile response to serotonin and a lower response to PGF2alpha than the ovarian portion. Oxytocin induced similar responses in both uterine segments. The uterine ovarian segment displayed a similar sensitivity to serotonin in all the estrous cycle stages, whereas in the cervical segment, influenced by estrogens in diestrus and proestrus, an increase in contractility was observed. According to these findings, serotonin might participate in the spermatozoa transport toward the oviduct. The higher response of the ovarian portion to prostaglandin F2alpha is in line with its role during labor and delivery.     

Effects of PGF2alpha and PGF2alpha, 1-15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey.

The effects of prostaglandin (PG)F2alpha and PGF2alpha, 1-15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF2alpha, 1-15 lactone were significantly (P less than 0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P less than 0.008) lower by the second day after the initial treatment with either PGF2alpha or PGF2alpha, 1-15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P less than 0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF2alpha, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF2alpha, 1-15 lactone. These data indicate that PGF2alpha, 1-15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF2alpha, 1-15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF2alpha.     

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.     

The influence of inhibited prostaglandin biosynthesis on post-ovulatory oviductal ova transport in sows

Changes in prostaglandin and progesterone concentrations after ovulation seem to affect reproductive functions in the sow. The influence of lowered prostaglandin levels on ova transport velocity through the isthmus part of the oviduct, and on progesterone concentrations, was studied during the second estrus after weaning in thirteen purebred Yorkshire multiparous sows. To determine the time of ovulation transrectal ultrasonographic examination was performed. In the second estrus, six sows were given intravenous injections of flunixin meglumine (2.2 mg/kg body weight) every sixth hour from 4 to 8 h after time of ovulation until about 48 h after ovulation, at which time the sows were slaughtered. Blood samples were collected every second hour from about 12 h before ovulation until slaughter. Progesterone and prostaglandin F2alpha (PGF2alpha) metabolite levels were determined. Immediately after slaughter the isthmus part of the oviducts were cut into 3 equally long segments and the number of ova in each segment, and in the upper part of the uterine horns, was determined. Before start of treatment, PGF2alpha metabolite levels were similar in the 2 groups (P=0.84). In the treatment group, PGF2alpha values dropped to below the detection limit immediately after start of treatment, whereas in the control group the concentrations were quite stable throughout the sampling period (P=0.005). Ova recovery rate was 94% in the treatment group and 95 % in the control group. At time of slaughter, in the treatment group ova had on average passed 2.1 segments whereas in the control group the ova had passed 2.5 segments (P=0.57). The progesterone levels increased continuously in both groups after ovulation but there was no difference in the mean progesterone concentrations between the two groups before (P=0.96) or after (P=0.58) ovulation. It can be concluded that the transport of ova through the isthmus part of the oviduct is unaffected by an inhibition of prostaglandin synthesis immediately after ovulation. Furthermore, the post-ovulatory progesterone profile seems unaffected by lowered PGF2alpha levels.     

Serum PGF2 alpha levels during late pregnancy, labour and the puerperium

The serum prostaglandin (PG) F2alpha levels of women in the last trimester of pregnancy have been measured and compared with the levels found in samples taken during labor, during the 1st week postpartum, and from nonpregnant women. The laboratory procedures for drawing the samples and making the radioimmunoassay measurements are explained. 40 samples were taken during late pregnancy, 46 during labor, 7 during the 1st week postpartum, and 8 from nonpregnant women. The results are graphed. PGF2alpha levels during late pregnancy resemble those found in nonpregnant women. A significant rise (p.05) occurs during labor, most markedly during the late 1st stage. Levels during the 1st week postpartum were found to be very low. There was no difference between serum levels during the 33rd-36th weeks and those found during weeks 34-40. Serum levels did not differ according to whether labor was spontaneous, induced by artificial rupture of fetal membranes and infusion of Syntocinon, or merely accelerated by syntocinon infusion. This indicates that PG release occurs as a result of labor rather than as a triggering mechanism for the onset of labor. The highest levels of serum PGF2alpha seem to be associated with the time of greatest uterine activity and the period of greatest cervical stretching.     

Progesterone levels and litter performance of sows following postpartum administration of prostaglandin F(2alpha)

A total of 101 sows was used to examine postpartum progesterone levels and litter performance following administration of 15 mg prostaglandins F(2alpha) (PGF(2alpha) n = 48) given within 12 h after farrowing. Daily blood samples and rectal temperatures were taken from all sows during the first 3 d post partum. Plasma progesterone (P(4)) concentrations were determined by radioimmunoassay (RIA). Regardless of treatment, plasma P(4) levels for all sows decreased in a similar fashion over the 3 d sampled. Mean (+/- SEM) P(4) on Day 2 (0.55 +/- 0.06 ng/ml) and Day 3 (0.38 +/- 0.04 ng/ml) were lower (P<0.01) than on Day 1 (0.98 +/- 0.08 ng/ml). Rectal temperature did not differ between PGF(2alpha) treated and nontreated sows nor was it different over the days measured. Litter characteristics, including survival rates on Day 7 and at weaning, and body weight on Days 3 and 35, were not affected by treatment. It was concluded that PGF(2alpha) administration to sows within 12 h post farrowing had no affect on the rate of luteal regression, as determined by P(4) concentration, nor on subsequent litter performance.     

Effect of mifepristone on pregnancy,pregnancy-specific protein B (PSPB), progesterone,estradiol-17beta,prostaglandin F2alpha (PGF2alpha) and prostaglandin E (PGE) in ovariectomized 90-day pregnant ewes

The objective of this experiment was to determine the effect of mifepristone, a progesterone receptor antagonist, on pregnancy and secretion of steroids, pregnancy-specific protein B (PSPB) and prostaglandins at mid-pregnancy in ewes. Ninety-day pregnant ewes were ovariectomized (OVX) and treatments were initiated 72 h post-OVX. Ewes received (1) vehicle, (2) prostaglandin F2alpha (PGF2alpha, 8 mg/58 kg/bw, i.m.) 84 h post-OVX, (3) mifepristone (50 mg intrajugular at 72, 84, 96, and 108 h post-OVX), (4) mifepristone (50mg) + PGF2alpha, (5) mifepristone (100 mg intrajugular at 72, 84, 96, and 108 h), and (6) mifepristone (100 mg) + PGF2alpha. Ewes treated with vehicle or PGF2alpha alone did not abort (P > or = 0.05). But, 60, 80, 60, and 100% of ewes treated with mifepristone (50 mg), mifepristone (50 mg) + PGF2alpha, mifepristone (100 mg), and mifepristone (100 mg) + PGF2alpha, respectively, aborted (P < or = 0.05). Profiles of progesterone, estradiol-17beta, prostaglandin E (PGE), or PSPB did not differ (P > or = 0.05) among treatment groups. Profiles of PGF2alpha of treatment groups receiving mifepristone with or without PGF2alpha differed (P < 0.05) from vehicle or PGF2alpha alone-treated ewes. It is concluded that progesterone actions are necessary to suppress uterine/placental secretion of PGF2alpha and that maintenance of critical progesterone: estradiol-17beta and PGE:PGF2alpha ratios are necessary for maintenance of pregnancy.     

Effect of prostaglandins on luteal function during early pregnancy in pigs.

Luteal cells were obtained by digestion of luteal tissue of cyclic (day 12) and early pregnant (days 12, 20 and 30) pigs. Suspensions of the dispersed luteal cells (5 x 10(4) cells ml-1) were incubated for 2 h in minimum essential medium (MEM) alone (control) and MEM with different concentrations of prostaglandin F2 alpha (PGF2 alpha) and PGE2 (0.01, 0.1, 1, 10, 100 and 1000 ng ml-1) and luteinizing hormone (LH) 100 and 1000 ng ml-1, or with combinations of LH + PGF2 alpha and LH + PGE2. Net progesterone production was measured in the incubation media by direct radioimmunoassay. The overall response pattern of the luteal cells to exogenous hormones on day 12 of the oestrous cycle and pregnancy differed (P < 0.05) from treatment on day 20 and 30 of pregnancy. In general progesterone production was higher (P < 0.05) and the response to PGF2 alpha and PGE2 treatment was most obvious on day 12 of the oestrous cycle and pregnancy. Overall, PGF2 alpha stimulated progesterone production in a dose-dependent manner (P < 0.05). The response to PGE2 was of a quadratic nature (P < 0.05) in which the lowest and the highest doses of PGE2 were associated with a greater production of progesterone than were the intermediate doses. Treatment of luteal cells with PGF2 alpha + LH or PGE2 + LH caused overall inhibition (P < 0.05) of progesterone production compared with treatment with each hormone alone. This interaction was not affected by the dose of LH used. These findings indicate that PGF2 alpha and PGE2 are involved in the autocrine control of corpus luteum function.     

Steroidogenic enzyme content and progesterone induction by cyclic adenosine 3',5'-monophosphate-generating agents and prostaglandin F2 alpha in bovine theca and granulosa cells luteinized in vitro.

In vitro luteinization of bovine granulosa (LGC) and theca (LTC) cells was achieved by culturing cells with forskolin (10 microM) and insulin (2 micrograms/ml) for 9 days. This treatment induced the presence of cytochrome P450scc and adrenodoxin in both cell types, but to substantially higher levels in LGC than in LTC. Forskolin dose-dependently stimulated the secretion of progesterone and cAMP after 3 h of incubation in both cell types although LGC were less sensitive to this stimulation than were LTC. Only LTC were responsive to LH, in accordance with their higher LH/hCG binding capacity. Both prostaglandin F2 alpha (PGF2 alpha) and phorbol 12-myristate 13-acetate (TPA) increased progesterone production during 3 h incubation of LGC and LTC, and treatment with staurosporine (a protein kinase C inhibitor) reversed this effect. Neither TPA nor PGF2 alpha alone affected cAMP levels but each acted synergistically with forskolin to increase cAMP accumulation. These results indicate that 1) elevated progesterone output from LGC is related to steroidogenic enzyme level; 2) bovine LH (up to 100 ng/ml) does not provoke a response in LGC due to their low LH/hCG binding capacity; 3) cAMP-protein kinase A and protein kinase C pathways are both involved in progesterone production by LGC and LTC, possibly by enhancing cholesterol transport.     

Increases in the oxytocin-induced prostaglandin F2 alpha response and reduction in the concentrations of endometrial oxytocin receptors in ewes in response to progesterone.

Ovariectomized ewes were given progesterone and oestrogen priming as steroid pretreatment and subsequently treated with progesterone, prostaglandin F2 alpha (PGF2 alpha), or both. In Expt 1, plasma concentrations of the metabolite 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured after an i.v. injection of oxytocin. There was little PGFM response in the untreated control ewes or in the pretreated ewes. Treatment with PGF2 alpha alone had no effect (P greater than 0.05), whereas treatment with progesterone either alone or with PGF2 alpha significantly (P less than 0.05) increased the uterine PGFM response to oxytocin. In Expt 2, chronically ovariectomized ewes had high concentrations of endometrial oxytocin receptors. Treatment with PGF2 alpha alone did not alter the concentrations of the receptors. Treatment with progesterone either alone or with PGF2 alpha significantly (P less than 0.05) reduced the concentrations of the receptors. It is concluded that progesterone promotes the PGFM response to oxytocin, but simultaneously suppresses the concentrations of endometrial oxytocin receptors.