Fall In Plasma Progesterone Research Articles

Structural Regression of the Rat Corpus Luteum of Pregnancy: Relationship with Functional Regression, Apoptotic Cell Death, and the Suckling Stimulus

The nature of the structural regression of the corpus luteum of pregnancy (PCL) was investigated in rats from day 19 of pregnancy (PRG19) through day 6 postpartum (PP6). A pre-partum decrease in tissue weight of the PCL during the last 4 days of pregnancy was apparent (nearly a 40% decrease) and seemed to parallel the fall in plasma progesterone. The PCL in normally lactating rats further experienced a gradual decrease in the postpartum period, but the reduction was significantly slowed by PP6 in non-lactating rats that were forced to wean from the parturient day (PPO). TUNEL analysis revealed that apoptotic cell death in the regressing PCL showed a 3-4 fold increase in signals after parturition (on PP3) but was fairly limited. Instead, luteal steroidogenic cells came to have cytoplasmic vacuoles by PRG21, and vacuoles increased through PP3. A decelerated decrease in PCL weight following forced weaning was potentially reversed by repeated administration of exogenous prolactin (10 IU) twice daily. This study adds evidence that structural regression of the rat PCL 1) starts to occur before the completion of functional regression, 2) involves a modest incidence of TUNEL-reactive apoptosis, and 3) is promoted by the suckling stimulus, presumably through the effects of prolactin.

Disrupted secretory activation of the mammary gland after antenatal glucocorticoid treatment in sheep

Antenatal glucocorticoids are administered to women at risk of preterm delivery to prevent neonatal respiratory morbidity. The effects of exogenous glucocorticoids on the development of lactation are unknown. This study investigated the effects of a single dose of antenatal glucocorticoids on secretory activation in sheep before and after parturition. Pregnant ewes (N=36) were randomised to receive either medroxyprogesterone acetate (MPA) at 118 days of pregnancy and betamethasone at 125 days (BETA group), MPA at 118 days and saline at 125 days (MPA group) or saline at 118 and 125 days (SALINE group). The concentration of lactose, progesterone, cortisol and prolactin in maternal plasma was measured during pregnancy. After term parturition, the concentration of lactose in milk and maternal plasma was measured daily for 5 days. Lambs were weighed at birth and at 5 days of age; milk volume was measured on day 5. The concentration of lactose in maternal plasma increased significantly after betamethasone administration, corresponding to a fall in plasma progesterone. No changes in lactose were observed in MPA or SALINE ewes. Transient decreases in cortisol and increases in prolactin were observed in the BETA group, but not in either the MPA or SALINE group. After parturition, BETA ewes experienced reduced milk yield and lamb weight gain, and delayed increases in milk lactose levels compared with MPA and saline controls. This study demonstrated that, in sheep, antenatal glucocorticoid administration disrupted secretory activation, causing precocious mammary secretion before parturition and compromising postpartum milk production and lamb growth.

Changes in Rat Uterine and Cervical Phospholipase A2 Activity Following Progesterone Agonist or Antagonist Administration at Term

Our previous study revealed that a fall in plasma progesterone (P(4)) level was associated with a transient increase in cytosolic phospholipase A(2) (PLA(2)) activity and prostaglandin F(2)alpha level in the rat uterus and cervix during natural parturition. This study determined the changes in the PLA(2) activities during modulated occurrence of delivery by P(4) antagonist or agonist late in pregnancy. In rats undergoing P(4) antagonist-induced preterm delivery, the PLA(2) activities of both uterine and cervical cytosol significantly decreased 12 h after the challenge and tended to be attenuated within 72 h. The plasma P(4) level altered in a similar pattern. Blockade of delivery by chronic treatment with P(4) agonist was not associated with changes in uterine PLA(2) activity compared with that in normally delivering rats, although there was a persistent rise in cervical PLA(2) activity. The obtained data indicates that the PLA(2) activities in rat uterine and cervical cytosol are not regulated solely by P(4) and that delivery can occur without activation of this enzyme.

Mouse placental prostaglandins are associated with uterine activation and the timing of birth.

We explored a potential mechanism linking placental prostaglandins (PGs) with a fall in plasma progesterone and increased expression of uterine activation proteins in the mouse. PG endoperoxide H synthase 2 (PGHS-2) mRNA expression increased in placenta in late gestation in association with an 8-fold increase in PGF(2alpha) concentration, reaching a peak on Gestational Day (GD) 18. This peak coincided with the final descent in plasma progesterone and birth on GD 19.3 +/- 0.2. Implantation of a progesterone-releasing pellet in intact pregnant dams on GD 16 delayed birth at term until GD 20.9 +/- 0.4 and inhibited the GD 18 increase in placental PGF(2alpha) levels in conjunction with a delayed fall in plasma progesterone that reached its lowest level 1 day after term birth. The mRNA levels of uterine activation proteins, connexin-43 (CX-43), oxytocin receptor, PGF(2alpha) receptor (FP), and PGHS-2, and the concentration of uterine PGF(2alpha) all increased at normal term birth. At progesterone-delayed term birth on GD 19.3, even though tissue PGF(2alpha) concentrations were at the same high levels observed at normal term birth, CX-43 and FP mRNA levels were lower than those at normal term birth, thereby possibly contributing to the delay of birth. These data are consistent with the hypotheses that fetal placental PGs affect the timing of birth by hastening luteolysis, that uterine activation initiates labor, and that birth may be delayed by blocking or decreasing the expression of two of the uterine activation proteins.

Use of vaginal electrical resistance (VER) to predict estrus and ovarian activity, its relationship with plasma progesterone and its use for insemination in buffaloes

In three experiments we studied the baseline and changes in VER during different natural estrous cycle stages (n=146) in ovarian structures and in plasma progesterone during estrus induced by prostaglandin injection (n=16) and the VER at insemination (n=90) in an attempt to predict estrus, ovulation and the best VER range for inseminating buffaloes for optimum conception. The baseline VER was classified on the basis of ovarian findings and estrous cycle stages. The mean VER during estrus, metestrus, diestrus, proestrus and anestrus was 32.68 ± 0.46, 41.26 ± 1.17, 50.23 ± 0.55, 43.20 ± 0.64 and 55.86 ± 0.57 ohms, respectively. There was a significant difference (P<0.01) between the VER except those between metestrus and proestrus. The ANOVA for VER over estrous cycle stages showed a highly significant (P<0.01) effect of stage of estrous cycle on VER in buffaloes. The percent decrease in VER was more pronounced from diestrus to estrus. In the second part of the study plasma progesterone profiles and the appearance of estrus in buffaloes induced to estrus using two dose schedules and routes of PGF 2α administration showed that luteolysis and estrus induction was slower in the 10 mg IVSM route (Intra Vulvo Submucosal) (only 60% animals evinced estrus in 48 to 72 hours) as compared to the 25 mg IM route (83.33% evidenced estrus in 48 to 72 hrs). Fall in plasma progesterone was synchronous to a fall in VER, the correlation (0.65) between them being positive and significant (P<0.01). After ovulation the VER started rising, showing a distinct relationship between VER and ovulation. By using VER, an additional 36.6% of the buffaloes could be detected in estrus. In the third part of the study, insemination of buffaloes induced to estrus (n=11) and normal-estrus buffaloes (n=79) showed that the overall conception rates to single insemination when the buffaloes were inseminated at the VER range of 26 to 30, 31 to 35 and 36 to 40 ohms were 81.48, 58.97 and 16.66%, respectively. Buffaloes showing VER from 31 to 35 ohms and 36 to 40 ohms also evidenced atypical and Null fern pattern in the cervicovaginal mucus. The study proved that VER can be used successfully to predict the stage of estrous cycle, ovarian status and ovulation; and insemination at a low VER distinctly improves the conception rates in buffaloes.

Neutralization of relaxin within the brain affects the timing of birth in rats.

Experiments were performed to determine whether neutralization of relaxin in the brain, by injecting monoclonal antibodies to rat relaxin into the ventricular system of the brain, affected either the timing or the processes of birth in rats. Pregnant rats were injected daily through a chronically implanted intracerebroventricular cannula either with a specific monoclonal antibody raised against rat relaxin from days 12-22 of gestation or with an antibody raised against fluorescein as a control. The rats were watched closely from the afternoon of day 20 of pregnancy, and the process of birth was observed. No sign of dystocia was observed in any of the rats in the experiment. Neutralization of endogenous relaxin caused a significant decrease in the length of gestation (505.4 +/- 3.1 h) compared with that in rats treated with PBS (524.6 +/- 0.5 h) or that in rats treated with a nonspecific antibody (525.9 +/- 0.7 h). The time to the onset of delivery was also shorter in the relaxin-neutralized group (507.8 +/- 1.1 h) compared with that in either PBS-treated (526.5 +/- 0.6 h) or fluorescein antibody-treated (525.3 +/- 0.7 h) animals. In contrast, there was no significant effect of the relaxin antibody on length of straining, duration of parturition, delivery interval, live birth rate, or body weight of the neonates. Premature delivery in the relaxin-neutralized group was accompanied by a 24-h advance in the fall in plasma progesterone. These data support the hypothesis that there may be a central relaxin system that is independent of the peripheral relaxin system. Central relaxin may have a significant physiological role on the timing of pregnancy in the rat, but does not affect the course of labor once it has started.

The effect of cloprostenol in non-pregnant and pregnant Norwegian semi-domestic reindeer (Rangifer tarandus tarandus L)

Abstract Two non-pregnant and five pregnant 1.5-year-old semi-domestic reindeer were used to study the effect of cloprostenol given during the luteal phase of the oestrous cycle, or at two stages of pregnancy (early December, n = 3, and mid-January, n = 2). Blood samples were collected at 3-hourly intervals from immediately prior to treatment until 6–8 days after treatment, after which blood samples were collected every second day. Prior to each blood collection, the animals were observed for signs of oestrus. Plasma progesterone, oestradiol-17β, luteinizing hormone (LH) and 15-ketodihydro-PGF 2α were analyzed to characterize variations in ovarian function. Treatment with cloprostenol resulted in an immediate and rapid decrease in plasma progesterone concentrations in all treated animals. The fall in plasma progesterone was associated with increase in 15-ketodihydro-PGF 2α . Oestrus, indicated by standing behaviour, was observed on three out of four occasions in the two non-pregnant animals. The average duration of standing behaviour (oestrus) was 27 h (range: 24–30 h). Of the pregnant females that were treated with cloprostenol in the beginning of December ( n = 3), two aborted between 72 and 96 h after treatment. One of these developed pyometra after abortion. In one female the foetus died 2 days after treatment, but was retained within the uterus until slaughter 2.5 months later. One of the two females that were treated in mid-January aborted between 62–65 h after injection. The other female retained a live foetus until slaughter in February. There were few endocrinological differences between animals that aborted and those that did not, though aborting animals had lower progesterone concentrations for a longer period of time after treatment. It was concluded that cloprostenol can be used during the luteal phase of the oestrous cycle to induce luteolysis and oestrus. When given during pregnancy, cloprostenol can induce abortion, though undesired side effects make it inappropriate for practical use.

Localization of oestradiol, progesterone and oxytocin receptors in the uterus during the oestrous cycle and early pregnancy of the ewe.

Uterine tissue samples were collected from 47 ewes at various stages of the oestrous cycle and early pregnancy (until day 21) and during seasonal anoestrus. Cryostat sections were immunostained to determine the localization of oestradiol and progesterone receptors using specific monoclonal antibodies. Oxytocin receptors were localized by autoradiography in sections from the same ewes using the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]- vasotocin. Plasma progesterone measurements were made during the preceding cycle up to the time of slaughter. Oestradiol receptor concentrations were maximal in all regions of the tract at oestrus. Immunostaining of the luminal epithelium, superficial glandular epithelium, stroma and myometrium decreased in the early luteal phase but was maintained for longer in the deep glands. Progesterone receptor immunostaining in the luminal epithelium and superficial glands developed in the early luteal phase (days 1-2) with a somewhat later appearance in the deep glands (days 5-7). Progesterone receptor concentrations in the stroma and myometrium also reached a maximum in the early luteal phase. Myometrial staining was clearly maintained throughout the luteal phase whereas stromal staining was variable between ewes. For both oestradiol and progesterone receptors no differences were apparent between pregnant and non-pregnant ewes between days 2 and 12, but pregnant ewes did not show the general increases in oestradiol receptor staining associated with luteolysis on days 14-15. Oxytocin receptors first developed in the luminal epithelium of non-pregnant ewes on day 14 of the cycle and spread to the superficial glands, caruncular stroma, deep glands and myometrium at oestrus before decreasing in reverse order on days 1-2. Specific binding was not detectable on days 5-12 of the cycle or on days 14 or 21 of pregnancy. The appearance of oxytocin receptors in the luminal epithelium on day 14 preceded that of both the oestradiol and progesterone receptors in the epithelial cells and the fall in plasma progesterone. It was followed by the development of oestradiol and oxytocin receptors in the superficial glands, deep glands, caruncular stroma and myometrium, with the two receptor populations showing a significant positive association in these tissues. The loss of oxytocin receptors in all regions occurred as plasma progesterone levels were increasing, but the association between these two variables was only significant in the superficial glands. The development of progesterone receptors in different tissues could not be explained on the basis of either oestradiol receptor content or plasma progesterone.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in the extensibility of the ovine cervix uteri following infusion of estradiol-17 β at term

Failure of the cervix to dilate is an important cause of dystocia in the ewe and other mammals. It is therefore important to develop objective methods of assessing the cervical state to understand how cervical softening is regulated. The extensibility (creep) of standard sized strips of ovine cervical tissue was measured in vitro using a creep testing device. There was a three-fold increase in the extensibility of the tissue taken from ewes during labor compared to saline treated controls ( P < 0.05). Infusion of estradiol-17β (E 2β) for 18 h commencing on day 145 of gestation caused a marked increase in extensibility of the tissue ( P < 0.05). Increase in extensibility was associated with a rise in PGFM and fall in plasma progesterone. Sodium meclofenamate (MFA) infused simultaneously with E 2β, blocked the E 2β induced softening of the cervix despite the low plasma progesterone levels. Similarly cervices from sheep receiving MFA alone had low extensibility. E 2β-induced softening of the ovine cervix appears to be modulated in part by prostaglandins.

The use of lower doses of the prostaglandin analogue, cloprostenol, for oestrus synchronization in heifers

In an attempt to reduce costs for cattle oestrus synchronization, the use of lower doses (50 and 25% of the conventional dose) of the prostaglandin F 2α analogue, cloprostenol, given by either intramuscular (IM) or intravulvo-submucosal (IVSM) injection, was investigated. There were no differences in the luteolytic response, as measured by either the fall in plasma progesterone or onset of oestrus, between lower cloprostenol doses administered by either method and 500 μg given by IM injection.

Changes in plasma progesterone concentrations from Days 17 to 42 of gestation in mares maintaining or losing pregnancy

Plasma progesterone concentrations were measured in 179 mares bled on alternate days commencing with a positive pregnancy diagnosis on Days 17 to 18 after ovulation and concluding on Days 42 to 45. During this period 17 mares (10 per cent) lost their pregnancies, 11 before Day 25. In 15 mares the timing of the pregnancy loss could be determined with adequate accuracy; in only one did a decline in progesterone precede the loss. Thus pregnancy loss between Days 17 and 42 was rarely caused by a fall in plasma progesterone.

The relationship between declining plasma progesterone levels and increasing luteinizing hormone pulse frequency in late gestation in the rat.

The object of this study was to determine whether the increase in LH pulse frequency and mean blood LH levels on day 22 of pregnancy in the rat is due to the precipitous fall in plasma progesterone (P) levels that occurs late in gestation. On day 20 of pregnancy two groups of animals with indwelling jugular cannulae were implanted sc with empty or P-containing Silastic capsules. Blood samples were withdrawn 0.5 h before and 5.5 h postimplantation on day 20 (0800 and 1400 h), at 1400 h on day 21, and at the end of the study between 1200-1300 h on day 22 to follow the time course of changes in plasma P levels over this 2-day period in both groups. These groups were bled on day 22 for 3 h between 0900-1200 h for analysis of pulsatile LH release. A third group not implanted with Silastic capsules was bled on day 20 for 3 h; plasma P levels in these rats bled on day 20 did not differ from the preimplantation values observed in either group of capsule-implanted rats. In empty capsule-implanted animals, plasma P values declined slightly from days 20 to 21 and were dramatically reduced between days 21 and 22. In contrast, after implantation of P capsules, plasma P levels were elevated on day 20 and remained elevated on day 21 compared with preimplantation values. Although these increased plasma P values declined between days 21 and 22, reflecting a decrease in endogenous P secretion, they were nonetheless comparable to day 20 values due to the presence of the P-containing capsules. Plasma estradiol values did not differ significantly between any of the experimental groups. In the empty capsule group bled on day 22, mean blood LH levels and LH pulse frequency were significantly higher compared to day 20 values, at a time when plasma P levels had fallen significantly from day 20 values. However, in the P capsule group, mean blood LH levels and LH pulse frequency on day 22 were significantly lower than values in the empty capsule group and were not different from the low values on day 20. Thus, preventing a decline in plasma P values to the low levels normally found on day 22 prevented the increase in LH pulse frequency and mean blood LH levels normally seen at this time of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships between plasma progesterone levels and testicular testosterone production in the rat fetus: effects of maternal ovariectomy.

The present study was performed to examine whether circulating progesterone regulates testicular testosterone production in the fetal rat. Progesterone levels in fetal plasma were found to increase from day 14.5 to day 16.5; thereafter they reached a plateau between days 16.5 and 18.5 (80 nmol/l) and decreased threefold between days 18.5 and 21.5. The addition of progesterone, within the range of normal plasma concentrations, induced a dose-dependent increase in testosterone produced in vitro by the testes on days 16.5 and 18.5 but not on day 20.5. However, in 18.5-day-old fetuses, individual plasma progesterone levels were not correlated with testicular testosterone production in vivo and in vitro. Furthermore, maternal bilateral ovariectomy induced a significant fall in plasma progesterone in 18.5-day-old fetuses; this was not associated with a reduction in plasma testosterone nor in testicular testosterone content, although the amount of testosterone secreted by the testis incubated in vitro was slightly but significantly reduced. It is concluded that circulating progesterone does not regulate testicular testosterone production in vivo although the testis may use plasma progesterone as a substrate. On day 18.5 after maternal ovariectomy, the decrease in plasma progesterone levels was similar in fetuses and mothers, suggesting that most fetal progesterone originates from maternal plasma.

The effect of medroxyprogesterone acetate on premature labor in the sheep

The ability of medroxyprogesterone acetate to delay premature delivery was investigated in nine chronically catheterized pregnant sheep (125 to 130 days' gestation). Catheters were placed for measurement of intrauterine pressure and uterine vein concentrations of progesterone, 17β-estradiol, and 15-keto-13,14-dihydroxyprostaglandin F2α. Premature parturition was induced in all animals by infusion of dexamethasone (1 mg/24 hours) to the fetus. Three ewes served as controls, three ewes received oral medroxyprogesterone acetate (5 mg/kg/day) 48 hours prior to the start of and during dexamethasone early medroxyprogesterone acetate), and the remaining three animals received oral medroxyprogesterone acetate 12 hours after the onset of dexamethasone infusion (late medroxyprogesterone acetate). The engths of time from dexamethasone until the onset of labor and from dexamethasone until delivery were compared, and were significantly longer for each group compared to control times. Of all endocrine events analyzed, the fall in plasma progesterone was the most consistent in all groups, showing that animals with rapid falls in progesterone levels (control group) tended to deliver earlier. These results demonstrate that medroxyprogesterone acetate can delay premature parturition in the sheep. Also medroxyprogesterone acetate appears to delay the endocrinologic events that normally occur at this time.

Placental control of ovarian immunoreactive relaxin secretion in the pregnant rat.

To investigate the control mechanisms for the secretion of relaxin in pregnant rats, the effects of the fetus, placenta, and uterus were studied. Plasma immunoreactive relaxin and progesterone were measured in pregnant rats, from days 8--1 post partum. On day 16 of pregnancy, groups of animals were subjected to removal of the fetuses, conceptuses (fetuses and placentae), or uteri. To determine whether there are extraovarian sources of circulating relaxin, a group of pregnant rats was ovariectomized on day 16. Immunoreactive relaxin was undetectable in the plasma of pregnant rats before day 10, and increased to a mean concentration of 0.52 +/- 0.01 (SEM) ng/ml on day 13. In control animals, immunoreactive relaxin levels remained at about this concentration throughout the remainder of pregnancy and declined rapidly post partum. The pattern of secretion of relaxin in fetectomized animals was similar to that in controls. In contrast, a significant decline in immunoreactive relaxin was seen, within 24 h after surgery, in those animals in which removal of the conceptuses or hysterectomy was performed. In these animals, immunoreactive relaxin was undetectable within 48 h after surgery and remained undetectable throughout the experimental period. In animals that were ovariectomized, immunoreactive relaxin was undetectable 24 h after surgery. Progesterone secretion in animals that had fetectomy or removal of the conceptuses performed was similar to that in controls. These groups showed a significant decline in progesterone on day 17 of pregnancy, and progesterone continued to decline until day 1 post partum. Progesterone in hysterectomized animals declined more abruptly than in either controls or other experimental groups. Ovariectomy resulted in a prompt fall in plasma progesterone. These results indicate that in the rat, the fetus is not needed for the maintenance of relaxin secretion throughout pregnancy, the placenta controls the ovarian secretion of relaxin. The uterus does not exert a tropic effect upon relaxin secretion, no extraovarian sources of circulating relaxin exist in the rat, and there is a divergence between progesterone and relaxin secretion during rat pregnancy.

Pattern of sexual steroids, prolactin, and gonadotropic hormones during prolactin inhibition in normally cycling women

In order to elucidate the role of prolactin (PRL) in the regulation of the human corpus luteum, a study was conducted in a series of female volunteers. Following a control cycle, two groups of five and four women were treated with bromocriptine, a prolactin (PRL) inhibitor; they received 5 and 7.5 mg. daily, respectively, for the length of another cycle. In two other subjects both doses were administered in consecutive cycles, whereas in two additional cases treatment was restricted to the postovulatory period until the onset of the next menses. Parameters examined were plasma PRL, LH, FSH, estradiol (E2-17β), and progesterone (PG), the latter being elaborated to a luteal index. Initiation of therapy at the onset of menstruation was followed by an immediate and significant (p < 0.001) fall in plasma PRL concentration. FSH, LH, and E2-17β were not modified by treatment, but a marked decrease in luteal PG in three out of five women receiving 5 mg. and in the four women receiving 7.5 mg. (p < 0.05) was recorded. This effect was only observed when treatment was extended to the entire length of the menstrual cycle, and was reversible on discontinuation of therapy. When administered in two consecutive cycles to the same person, 7.5 mg. induced a more marked fall in plasma PG when compared with the control and the 5 mg. dose. These results suggest that PRL physiologically influences the function of the human corpus luteum since its suppression to below-normal levels may cause defective PG synthesis by the ruptured follicle. The possible biological implications of this effect are discussed.

Interruption of early pregnancy with a silastic device containing (15S)-15-methyl prostaglandin F 2α methyl ester: Efficacy and mode of action

The efficacy of an intravaginally placed silastic device containing (15S)-15-methyl prostaglandin F2α methyl ester (15-Me-PGF2α) in inducing abortion was evaluated in 20 pregnant women who were no more than 50 days beyond the first day of their last normal menstrual period. Eighteen pregnancies were interrupted successfully. In 1 woman in whom an intrauterine pressure gauge had been inserted, abortion failed to occur; in another woman who failed to abort, an ectopic pregnancy was later discovered. All women who aborted developed gastrointestinal symptoms; most had severe abdominal cramping pain necessitating narcotic analgesia. Following insertion of the prostaglandin-containing device, the levels of serum hCG fell rapidly, reaching about one-fourth the baseline level within 24 hours. The fall in plasma progesterone and estradiol levels was less pronounced; plasma 17α-hydroxy-progesterone levels—although quite variable—increased during the first 2 hours but by 24 hours had fallen to an average value of 27.4% of the baseline level. Plasma levels of 15-Me-PGF2α, measured in 6 patients, varied greatly.

The effects of combined dexamethasone and indomethacin treatment on the outcome of pregnancy in the rabbit.

Pregnant rabbits were treated with dexamethasone, 6 mg/day i.m. from Day 21 until delivery, dexamethasone alone induced premature parturition (27.0 ± 0.6 S.D. days, P<0.001). These results confirm previous studies. In addition, the delay in parturition caused by indomethacin was found to be associated with a delay in the preparturient decline in plasma progesterone (treated higher than untreated on Day 30, P<0.05), supporting the view that prostaglandin-induced luteolysis plays a role in the physiologic termination of pregnancy. The results obtained with the animals which were treated with both dexamethasone and indomethacin were not different from those observed with dexamethasone treatment alone. There was no delay of the dexamethasone-induced decline of plasma progesterone or of the premature parturition (26.3 ± 2.5 S.D. days). These results and previous observations suggest that the suppression of plasma progesterone and the induction of parturition by dexamethasone in this species may differ from spontaneous parturition in regard to the role of prostaglandin synthesis in causing the fall in plasma progesterone.

LUTEOLYTIC EFFECTS OF PROSTAGLANDINS IN RAT PREGNANCY, AND REVERSAL BY LUTEINIZING HORMONE

ABSTRACT The influence of prostaglandin infusions on plasma progesterone (P) was determined in pregnant rats at various stages of gestation. Serial blood samples were collected from the right atrium through an indwelling catheter before, during and after prostaglandin (PG) administration. PGE2 and PGF 2α was given as intravenous infusions of 6 hours duration through the same catheter at rates varying from 0.33 to 5.5 μg/min (total dose: 125 to 2000 μg/rat). Control rats received an equal amount of 0.9 % saline solution. Prostaglandins suppressed plasma P levels at all stages of gestation, PGF2α being much more effective than PGE2. The effect of PGF2α was not dose-dependent above a threshold level of about 125 μg/rat. The decrease in plasma P was evident within 3 hours of the start of the infusion, with further decrease in the subsequent 3 hours of infusion. The degree of luteal suppression by PGF2α varied in the course of gestation, being greatest on days 10 and 18 of pregnancy and smallest on days 4 and 16. On days 10 and 18, plasma was reduced by 75 %, on the average, during the infusion of PGF2α with further decrease to 15 % of initial values within 24 hours. Pregnancy was terminated in these rats, but was maintained in most rats treated with PGF2α at other stages of gestation. Plasma P decreased, on the average, by 60 % during the infusion of PGF2α in all rats that remained pregnant, and progesterone concentrations remained at a level of 30 % of initial values for at least 2 days. Plasma P levels as low as 20 % of initial values were compatible with undisturbed gestation. Concomitant treatment with LH prevented the decrease in plasma P induced by PGF2α on days 4, 7 and 10, but had little effect on day 18. Prolactin, given alone or with oestradiol, was completely ineffective on day 10 but on day 4, prolactin had a marginal inhibitory effect on the PGF2α-induced fall in plasma progesterone.

Plasma progesterone changes in abortion induced by hypertonic saline in the second trimester of pregnancy.

SummaryPlasma progesterone levels were measured by a competitive binding method in a total of 177 blood samples obtained from 17 patients after the intra‐amniotic instillation of hypertonic saline for termination of a second trimester pregnancy. A mean fall in plasma progesterone of 51 per cent was observed before abortion of the fetus. There was a highly significant correlation between falling progesterone values and the instillation‐abortion interval (p&lt;0.001).