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PubMed2000

Inter-relationships between endothelin and prostaglandin F2alpha in corpus luteum function.

In cattle and other species, the corpus luteum plays a central role in the regulation of cyclicity and maintenance of pregnancy. In the absence of fertilization and implantation, the corpus luteum undergoes functional and morphological regression or luteolysis. Luteal regression is initiated in domestic ruminants by surges of prostaglandin F2alpha (PGF2alpha) from the uterus. Despite intensive investigation, the mechanisms by which PGF2alpha causes luteal regression remain undetermined. Recent studies from several laboratories have demonstrated that endothelial cells and their product, endothelin 1, are required for the manifestation of the luteolytic effects of PGF2alpha. Experimental evidence strongly supports the concept that luteal endothelin 1 inhibits luteal steroidogenesis and mediates the effects of PGF2alpha. Endothelin 1 caused a dose-dependent reduction in both basal and luteinizing hormone-stimulated biosynthesis of progesterone and prostacyclin, and an increase in PGF2alpha by ovine and bovine luteal cells. Specific receptors for endothelin 1 were identified on large and small bovine luteal cells, and the addition of specific endothelin receptor antagonists abolished the inhibitory effects of endothelin 1. Luteal endothelin 1 content increased as the cyclic corpus luteum aged, and the highest concentrations were observed during luteolysis. The amount of mRNA encoding endothelin 1 was greatly increased during the period of luteolysis. Gene expression for endothelin 1 was increased, in a time-dependent manner, in corpora lutea collected from heifers and ewes after exogenous administration of PGF2alpha. In heifers, exogenous PGF2alpha resulted in increased luteal output of endothelin 1. In ewes, the luteolytic effects of PGF2alpha were mitigated by pretreatment with a specific endothelin receptor antagonist. Administration of endothelin 1 or a sub-luteolytic dose of PGF2alpha to ewes reduced concentrations of jugular venous progesterone but did not shorten luteal lifespan. However, a combination of endothelin 1 and PGF2alpha acted synergistically to bring about complete luteolysis and reduced lifespan of the corpus luteum. In summary, endothelin 1 appears to have a direct effect on luteal cells in cattle and sheep, and it plays an essential role in mediating the luteolytic effects of PGF2alpha.

Animals↗

PubMed1978

Danazol as a luteolytic agent.

Danazol, a synthetic 2,3-isoxazol derivative of 17 alpha-ethinyltestosterone, was administered to healthy nonpregnant volunteers to determine wheter a luteolytic effect could be detected by observation of cycle length, duration of the luteal rise, and luteal steroidogenesis. Danazol administration resulted in a decreased duration of the luteal rise and a decrease in progesterone output in three of four subjects, but no decrease in total cycle length. The administration of human chorionic gonadotropin during danazol administration increased progesterone output. Therefore, danazol would be unlikely to be effective as a luteolytic contraceptive agent.

Chorionic Gonadotropin↗

PubMed1997

Interaction of prostaglandin F2alpha and gonadotropin-releasing hormone on progesterone and estradiol production in human granulosa-luteal cells.

This study examined the effects of prostaglandin-F2alpha (PGF2alpha), GnRH, and their interactions on steroidogenesis in human granulosa-luteal cells (GLCs). Human GLCs collected from in vitro fertilization patients were cultured for one or eight days, followed by a 24-h treatment period, after which media were collected and radioimmunoassayed for progesterone and estradiol. In the first experiment, GLCs were treated with vehicle, PGF2alpha (10(-9) M), GnRH (10(-6) M), or PGF2alpha plus GnRH, with or without hCG (1 IU/ml). Neither PGF2alpha nor GnRH alone had a significant effect; however, the combination of PGF2alpha plus GnRH significantly stimulated steroidogenesis. Similarly, co-application enhanced the luteolytic effects of PGF2alpha. In a second experiment, PGF2alpha and GnRH concentration-response curves were crossed into a matrix of 49 separate treatments. Responses were plotted in three-dimensions and as two-dimensional "slices" that were analyzed statistically. In the presence of high concentrations of GnRH (10(-6) M), PGF2alpha stimulated progesterone production in a biphasic manner, as middle concentrations significantly stimulated (10(-9) M) whereas low and high concentrations did not. In the presence of middle concentrations of PGF2alpha (10(-9) M), GnRH significantly stimulated progesterone production in a linear concentration-dependent manner. Similar complexities were seen with respect to estradiol response. Thus, in the human GLC, GnRH potentiates the luteolytic effects of PGF2alpha, while it acts as a permissive factor for the luteotropic effects. Furthermore, we have revealed the complex interaction of these hormones using a three-dimensional experimental design.

Cells, Cultured↗

PubMed1980

Synergism of estrogen and bromergocryptine in the induction of luteolysis in cynomolgus monkeys (Macaca fascicularis).

Sequential administration of estrogen (40 microgram depoestradiol cypionate and estradiol benzoate) on cycle days 18--20 and bromergocryptine (CB-154; 0.5 mg/kg, twice daily) on cycle days 20-22 induced luteolysis in seven of nine cynomolgus monkeys, significantly shortened menstrual cycles (23.5 +/- 0.7 days), and caused a significant decline in plasma progesterone levels during the period of CB-154 administration. Two treated monkeys did not have shortened menstrual cycles, although a luteolytic effect on plasma progesterone was evident. One monkey with a late ovulation (confirmed by endocrine parameters and laparoscopic observation) was treated with the same regimen in the early luteal phase; this also resulted in a decline in plasma progesterone and a shortened luteal phase (11 days). Treatment with the estrogen or the CB-154 component alone had no effect on menstrual cycle length or plasma progesterone levels. Similarly, treatment with CB-154 throughout the luteal phase had no effect on luteal function. An abbreviated treatment consisting of 1 day of estrogen and 1 day of CB-154 administration gave some indication of a luteolytic effect. None of these treatments produced detectable side effects. These studies have demonstrated a synergism of estrogen and CB-154 in the induction of luteolysis in cynomolgus monkeys. The present regimen, because of the effectiveness and apparent lack of side effects, deserves further investigation for possible clinical application.

Animals↗

PubMed1975

Interactions between prostaglandin analogues and a receptor in bovine Corpora lutea. Correlation of dissociation constants with luteolytic potencies in hamsters.

The dissociation constants for the interactions between some prostaglandin analogues and a prostaglandin F2 receptor in bovine corpora lutea were determined. These values were compared to the antifertility potencies of these compounds in hamsters and the rates of metabolism by 15-hydro-syprostaglandin dehydrogenase. The most active analogues with regard to both affinity for the receptor and luteolytic potency were 17-phenyl-18, 19, 20-trinorprostaglandin F2alpha and 15-methylprostaglandin F2alpha. The alkyl side chain of prostaglandins could be modified considerably without altering the affinity for the receptor. In this way metabolism by 15-hydroxyprostaglandin dehydrogenase could be blocked. Some of these compounds -ad greatly increased luteolytic effects. Substitution of a phenyl group for the 3 terminal carbon units of the alkyl side chain of prostaglandins increased both the affinity for the receptor and the luteolytic activity in vivo. 7-oxa-13-prostynoic acid, an antagonist of the luteolytic effect of prostaglandin F2alpha in vivo was a weak competitive inhibitor of the interation between prostaglandin F2alpha and the receptor.

Animals↗

PubMed1996

Monitoring and controlling reproduction in captive common marmosets on the basis of urinary oestrogen metabolites.

Non-invasive methods for routine monitoring of reproductive states and reproduction control in large colonies of captive Callithrix jacchus have been developed. Immunoactive urinary oestrone-3-conjugates (E1C) were measured during non-conception cycles (n = 5) and pregnancy (n = 7). Using plasma progesterone levels to time ovulation, ovulation was quantitatively estimated by a) calculating the first E1C rise and b) by establishing an E1C threshold. Ovulation was thus defined as taking place 4 days preceding a) the first rise of E1C above follicular-phase levels, or b) a concentration > or = 4.5 micrograms E1C/mg creatinine. Early pregnancy could be determined after day 20 by continued luteal-phase levels of E1C. Secondly, the luteolytic effect of cloprostenol, injected over a wide range of doses and between days 1 and 64 after ovulation/conception, was analysed. Luteolysis was achieved when cloprostenol was administered after day 5 post-ovulation; the luteolytic effect was found not to be dose-dependent. The success of cloprostenol treatment was 87% as confirmed by endocrine monitoring. The methods described are effective and minimize intervention, and are therefore suitable for long-term applications, particularly in combination with behavioural studies.

Animals↗

PubMed1983

Corpus luteum regression induced by ultra-low pulses of prostaglandin F2 alpha.

In view of the pulsatile nature of PGF2 alpha secretion from the ovine uterus at the time of luteolysis, experiments were designed to examine the effect of pulsed infusions of PGF2 alpha on luteal function and to re-examine the minimal effective levels of PGF2 alpha required to induce luteolysis. To mimic physiological conditions, hour-long infusions of PGF2 alpha in increasing concentrations were given either 4 times in 19 h or 5 times in 25 h into the arterial supply of the autotransplanted ovary in conscious sheep on day 12 of an induced cycle. Blood flow and progesterone secretion rate from the ovary were used to monitor directly the luteolytic effect of administered PGF2 alpha. The concentration of LH in peripheral plasma was measured throughout each infusion experiment and the presence of a preovulatory peak of LH was used as an indicator of the permanence of luteal regression. Four pulses of PGF2 alpha in 19 h caused complete corpus luteum regression in only 1 of 4 animals whereas the addition of a fifth pulse (5 pulses in 25 h) caused permanent regression in 4 out of 4 animals. Infusion of 5 hour-long pulses of saline or PGF2 alpha at a rate less than 0.04 microgram/h did not induce permanent suppression of progesterone secretion. The average total effective dose of PGF2 alpha required to induce luteal regression when given as 5 pulses was 1/40th of the amount currently regarded as the minimal effective one when given by constant infusion into the ovarian artery. In another series of experiments the luteolytic effect of a single hour-long pulse of 0.1 microgram/h PGF2 alpha given daily for either 3 or 4 days was investigated. A significant fall (ANOVA, F0.01) in progesterone secretion rate, which reached a nadir at 5.3 +/- 2.2 h (means +/- S.D., n = 15), was followed by a recovery of progesterone secretion rate. Permanent luteal regression did not occur with this protracted regimen, suggesting that a relatively short pulse frequency of PGF2 alpha over a minimal period of 24 h is a necessary condition for physiological regression of the corpus luteum in sheep.

Animals↗

PubMed2000

Progesterone on an oestrogen background enhances prolactin-induced apoptosis in regressing corpora lutea in the cyclic rat: possible involvement of luteal endothelial cell progesterone receptors.

Preovulatory surges of both prolactin (PRL) and progesterone have been suggested to be necessary for the induction of apoptosis in the regressing corpus luteum of the cyclic rat. The aim of these experiments was to study whether the administration of PRL and/or progesterone on the morning of pro-oestrus reproduces the regressive changes that happen in the cyclic corpus luteum (CL) during the transition from pro-oestrus to oestrus, and to analyse the temporal relationships between two characteristic features of structural luteolysis (luteal cell apoptosis and accumulation of macrophages). Cyclic rats (treated at 0900 h with an LHRH antagonist to block LH secretion) were injected at 1000 h with PRL and progesterone and killed at 0, 30, 60, 90 and 180 min after treatment. The number of apoptotic cells increased progressively from 60 min after treatment onward in hormone-treated rats, whereas the number of macrophages did not change throughout the period of time considered. Rats injected with PRL plus progesterone showed significantly greater numbers of apoptotic cells than those injected with PRL alone. The luteolytic effects of progesterone were in keeping with the presence of luteal endothelial cells showing progesterone receptor (PR) immunoreactivity in pro-oestrus. Treatment of rats during dioestrus and pro-oestrus with the specific antioestrogens LY117018 and RU58668 decreased the luteolytic effects of PRL and progesterone and the number of luteal endothelial cells immunostained for PR. These results strongly suggest that the preovulatory PRL surge and the preovulatory increase in progesterone together trigger structural regression of the corpus luteum. This seems to be dependent on oestrogen-driven cyclic changes in PRs in luteal endothelial cells.

Animals↗

PubMed1981

Induction of luteolysis by dihydrotestosterone in the pregnant rat.

A dihydrotestosterone (DHT) pellet (4 mg) inserted under each ovarian bursa on day 9 of pregnancy induced within 24 h, a 40% decline in serum progesterone (P) concentrations in rats; a further reduction was observed on days 12 and 15. Although P levels were significantly reduced by DHT treatment, fetuses remained alive on day 12. However, by day 15, complete abortion occurred in 75% of the rats, indicating that a decline in P secretion precedes abortion, To further determine whether the abortifacient action of DHT was due to its luteolytic effect, 20-cm DHT capsules were implanted subcutaneously in ovariectomized rats treated with 4 mg P and 0.5 micrograms of estradiol (E). Control rats were sham-operated and treated with empty capsules. DHT treatment induced complete abortion by day 15 only in rats with ovaries present, further indicating that DHT was not directly detrimental to the fetuses but acted on the ovaries to induce luteolysis. When DHT treatment was started on day 12, no luteolytic effect was detectable. To determine whether the effect of DHT was mediated by either a decrease in the ovarian production of E, a decline in luteal cell content of luteinizing hormone (LH) receptors or both, testosterone (T) levels in the peripheral circulation and E and P concentrations in the ovarian vein were measured on day 15 in rats implanted with two DHT pellets under the ovarian bursa on day 9. Luteal content of LH receptors was also measured on day 12 in similarly treated rats. DHT treatment had no effect on serum levels or on ovarian vein concentration of E, but induced a significant decrease in the ovarian vein levels of P. DHT also did not depress LH receptor content in corpora lutea. DHT levels in the ovaries increase significantly between days 18 and 22 of pregnancy, concomitant with the cessation of corpus luteum function. These results indicate that DHT possesses a potent luteolytic activity and could be involved in the luteolytic process in the pregnant rat.

Animals↗

PubMedDate not supplied

Effects of luteolytic doses of prostaglandin F2 alpha and cloprostenol on concentrations of progesterone, luteinizing hormone, follicle-stimulating hormone, glucose, insulin, growth hormone, thyroxine, prolactin and cortisol in jugular plasma of lactating dairy cows.

Three groups of five lactating dairy cows in the mid-luteal phases of oestrous cycles were given an injection (at time 0 h) of the naturally-occurring prostaglandin F2 alpha (PGF2 alpha) or cloprostenol (a synthetic analogue of PGE2 alpha) at doses recommended for inducing luteolysis, or injection vehicle. Concentrations of glucose and hormones in jugular plasma were measured from 26 h before to 12 h after the injections and the significance (P < 0.05) of the effects of the prostaglandins on these concentrations was determined. Both prostaglandins induced falls in progesterone concentration and rises in luteinizing hormone concentration; neither influenced follicle-stimulating hormone. PGF2 alpha increased glucose concentration; neither prostaglandin influenced insulin concentration. Both prostaglandins increased growth hormone concentration and resulted in declining thyroxine concentration. PGF2 alpha increased prolactin and cortisol concentration. There were, however, no significant differences between the effects of the two prostaglandins on any hormone (or glucose) concentration.

Animals↗

PubMed1980

Luteolytic activity of LHRH and [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide: a new and physiological approach to contraception in women.

The administration of five subcutaneous 250-microgram doses of luteinizing hormone-releasing hormone (LHRH) at 4-hour intervals on 1 or 2 consecutive days between days 1 and 9 following the spontaneous LH surge in normal women shortened the luteal phase from 1 to 4 days in 16 out of 17 treatment cycles. Treatment appeared to be more efficient when LHRH was administered on days 6 to 9 after the LH surge as compared with days 1 to 5. In fact, the luteal phase was shortened from 3.3 +/- 0.2 versus 1.4 +/- 0.2 days (P < 0.01) and the serum progesterone level was decreased to 44 +/- 5 versus 71 +/- 6% of control levels (P < 0.01) when the neurohormone was injected late as compared with early in the luteal phase. A similar luteolytic effect has been obtained after intranasal administration of 500 microgram of [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide at 0800 and 1700 h on one day between days 4 and 9 following the LH peak. In six women treated with the LHRH analogue during two consecutive cycles, the luteal phase was shortened by 2.6 +/- 0.4 days (range 0.5-4.5 days) and plasma progesterone levels were reduced to 61.3 +/- 9.2% of control. As determined by daily blood sampling for LH, FSH, estradiol, and progesterone, normal cycles occurred immediately after treatment. The present data indicate the luteolytic effect of treatment with LHRH or a LHRH agonistic analogue in normal women and support the interest of such a new and physiological approach for the control of corpus luteum function and menstrual cycle in women.

Administration, Intranasal↗

PubMed1986

Possibility of reducing the luteolytic dose of cloprostenol in cyclic dairy cows.

The administration of cloprostenol by intravulvosubmucous (i.v.s.m.) injection at 1 2 and 1 4 of the dose usually given by intramuscular (i.m.) injection, was tested in dairy cows for luteolysis and estrus synchronization. The i.m. injection was used in ten adult cows at the usual dose of 500 mug/animal. Eleven adult cows and 11 heifers were treated i.v.s.m. with a dose equivalent to 250 mug/animal and 125 mug/animal, respectively. Two injections of cloprostenol were administered 11 days apart to the cows not detected in oestrus after a single injection. Forty-three out of the total 46 animals were detected to be in dioestrus at the time of at least one of the injections, as reflected by the plasma progesterone concentrations at the time of treatments. Three out of the 43 animals injected during dioestrus were refractory to the luteolytic effect of cloprostenol; this appeared to be independent of the dosage and the route of administration (refractory cows were: one adult cow treated i.m. and two treated i.v.s.m. with 125 mug of cloprostenol). The mean time interval from injection to the onset of heat was 82.8 hours with a confidence limit for 95% of probability between 67.9 hours and 92.7 hours. The difference between treatments is not significant. The results suggest that in heifers and adult cows cloprostenol can be given i.v.s.m. route at a reduced dose of 1 4 of the usual 500 mug i.m. dosage without affecting the luteolytic effect of the drug or fertility.

Journal Article↗

PubMed1998

Luteolysis induced by a prostaglandin F2alpha analogue occurs independently of prolactin in the rat.

The hypothesis that prolactin exerts a stimulatory dominance over the luteolytic effect of prostaglandin (PG) F2alpha on corpus luteum maintenance and progesterone production was experimentally tested. A dose-dependent effect of the stable PGF2alpha analogue cloprostenol (dose range 200 ng(-5) microg) was found 12 h after s.c. injection, in Day 9 adult pseudopregnant rats: 1) LH receptor mRNA levels, as measured by RNase protection assay, were dramatically decreased (by 67%) by a single s.c. dose of 200 ng cloprostenol; and 2) serum progesterone levels were significantly (p < 0.05) decreased (by 43%) whereas 20alpha-dihydroprogesterone significantly (p < 0.05) increased (by 80%) initially at a 0.5-microg dose of cloprostenol. To study the integrated response to prolactin and PGF2alpha, we investigated the effect of cloprostenol treatment in sterile-mated female rats with or without circulating prolactin. Prolactin secretion was inhibited by s.c. injection of bromocriptine (1 mg) in the morning of the ninth day of pseudopregnancy. A group of rats was left prolactin-depleted; in another group prolactin was reintroduced by adding 8 IU ovine prolactin. It was found that after injection of 0.5 microg cloprostenol the LH receptor mRNA levels and the serum progesterone/20alpha-dihydroprogesterone ratio were not significantly different whether the rats had circulating endogenous/exogenous prolactin or were prolactin-depleted. Therefore, although prolactin exerts a stimulatory influence on both progesterone production and corpus luteum LH receptor gene expression, the conclusion is reached that prolactin alone cannot antagonize the luteolytic effect of PGF2alpha.

Animals↗

PubMed1993

Repeated administration of prostaglandin F2 alpha during the early luteal phase causes premature luteolysis in the pig.

Previous investigators considered pig corpora lutea refractory to the luteolytic effects of prostaglandin (PG) F2 alpha before Day 12 of the estrous cycle. This study was designed to determine whether multiple injections of PGF2 alpha would result in a sustained reduction of serum progesterone and luteolysis, leading to significant shortening of the estrous cycle and interestrous interval. On Days 5-10 of an estrous cycle, gilts (n = 4) received injections of 12.5 mg PGF2 alpha (dinoprost tromethamine) i.m. every 12 h, or vehicle (PBS; n = 4) according to the same schedule. Mean interestrous interval in PGF2 alpha-treated gilts was reduced (p < 0.001) to 13.3 +/- 0.5 days compared with 19.8 +/- 0.6 days for control gilts. Serum progesterone declined below 1 ng/ml by Day 10.5 in PGF2 alpha-treated gilts compared to Day 17.5 in control animals. Serum concentrations of estradiol-17 beta (E2) reached maximal levels in PGF2 alpha-treated gilts earlier (Day 12.5) in the cycle than in control gilts (Day 19.5). Peak E2 and LH concentrations coincided with the periestrous period, suggesting that PGF2 alpha-induced estrus is accompanied by normal follicular development and ovulation. These results demonstrate that the pig is susceptible to the luteolytic effects of PGF2 alpha before Day 12 if repeated injections are given from Day 5 through Day 10.

Animals↗

PubMed1996

Prolactin-induced regression of the rat corpus luteum: expression of monocyte chemoattractant protein-1 and invasion of macrophages.

Monocyte chemoattractant protein-1 (MCP-1) is a potential mediator of the recruitment of monocytes/macrophages into the regressing corpus luteum (CL). We investigated whether the luteolytic effect of prolactin in the rat is associated with the expression of MCP-1 and an invasion of monocytes/macrophages. Ovulation was induced in immature female rats by injection of eCG (5 IU, s.c.) at 30 days of age. All rats were hypophysectomized 3 days later. Rats received injections of ovine prolactin (250 micrograms, s.c.) at 12-h intervals on Day 9, 10, and 11 posthypophysectomy; controls received injection of vehicle. Rats were killed by decapitation 24, 48, or 72 h after the first injection of prolactin or vehicle. In rats treated with prolactin, immunoreactive MCP-1 was detected in the CL at 24 h after the first injection, and a consistent level of staining was reached by 72 h with immunodetectable MCP-1 diffused throughout individual CL. The number of monocytes/macrophages in the CL (mean +/- SEM) increased significantly after prolactin treatment, from 3.1 +/- 1.8 at 24 h to 49.3 +/- 8.2 at 72 h (p < 0.05), and the number of monocytes/macrophages was different from that in control, vehicle-treated rats at 72 h (10.3 +/- 4.1; p < 24 and 72 h in prolactin-treated rats (p < 0.05). It is concluded that a potentially important component of the luteolytic effect of prolactin in the rat is the expression of MCP-1 and invasion of monocytes/macrophages into the CL.

20-alpha-Dihydroprogesterone↗

PubMed1978

Pregnant mare's serum gonadotropin: V. Indomethacin or cortisone and the reversal of antifertility efficacy of pregnant mare's serum gonadotropin.

Pregnant mare's serum gonadotropin (PMSG) of 10 IU on day 5 of pregnancy induced luteal demise and consequently an absolute resorption of fetuses and placentae resulted on day 16 of pregnancy. Simultaneous regimen of PMSG and indomethacin or cortisone was found to be consistently effective in preventing the luteolytic effect of PMSG. The growth of the fetuses, placentae as well as corpora lutea was found to be parallel to controls. Similarly, shortening of the duration of pseudopregnancy to 10--12 days in the bilaterally hysterectomized rat by PMSG and its retaining the normal duration of 18--20 days in the presence of indomethacin tempt us to propose that the PMSG-induced luteolysis is possibly reflected through the release of prostaglandin at the ovarian level.

Animals↗

PubMed1985

Studies on the mechanism of action of antifertile PG in animal models.

Antifertile effects of PGF2 alpha, PGE2, PGE1, sulprostone and other PGs were evaluated in different pregnancy models in rats, guinea pigs and rhesus monkeys and the underlying mechanisms of action were investigated. Quantitative and qualitative species differences and pregnancy stage dependency were recorded. Basic regulatory differences of the pregnant uterus seem to exist in these species. In early pregnant rats, abortifacient effects were based on luteolytic effects, independent of the PG used. The myometrium was found to be refractory to the injected PG as long as serum progesterone levels were kept high. By contrast, in guinea pigs after the luteoplacental shift of progesterone secretion (tested after day 40 p.c.) and in rhesus monkeys even before this shift (tested day 20 p.c.) abortifacient effects were found to be exerted by direct stimulation of the myometrium. Uterine stimulation was possible in the presence of any level of serum progesterone. The induction of uterine PG synthesis was probably of importance supporting the expulsion. The role of obvious tissue damage within the conceptus remained uncertain. In contrast to rats there seems to be a pre-existing PG-sensitivity of the pregnant myometrium in guinea pigs and primates. In guinea pigs sensitivity slightly increased for E- but not for F-type PG toward term. Oxytocin sensitivity was found to increase by a factor of more than 100 between days 23-63 of pregnancy. Time dependent changes in uterine receptivity to PG and oxytocin may be considered as a regulatory principle which might permit parturition to occur in the presence of progesterone as an evolutionary adaptation to a placental progesterone secretion which cannot be abolished. It was concluded that in the presence of already established gradual uterine responsiveness to PG (and Oxytocin) during gestation efficient blocking mechanisms for uterine PG-formation must exist in order to explain uterine quiescence. Almost complete resistance of pregnancy to oestrogen which exists in humans, monkeys and guinea pigs was considered as to be pharmacological evidence of such a mechanism. The principles of endocrine control of the myometrium and its pharmacology seem similar in guinea pig and primate pregnancy. The guinea pig might therefore provide a relevant model to study potential drug effects on the regulatory balance of the pregnant uterus and also to achieve a better understanding of human uterine physiology.

Abortifacient Agents↗

PubMed1976

Luteolytic and abortifacient effects of serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha in early pregnancy.

Pregnancy was successfully terminated in 8 of 9 patients 5 to 6 weeks after the last menstrual period by serial intramuscular injections of 15(S)-15-methyl-prostaglandin F2alpha (15-ME-PGF2alpha). In one patient the treatment induced vaginal bleeding and a drop in hormone levels, but the patient did not completely abort and the uterus had to be evacuated. Serial intramuscular injections of 15-ME-PGF2alpha appeared to have some luteolytic effect, resulting in a significant drop in progesterone and estradiol levels. However, it is uncertain if the luteolytic effect of the prostaglandin was the precipitating factor in the abortion since the administration of 15-ME-PFG2alpha was accompanied by strong uterine activity which played a role in the abortion.

Abortifacient Agents↗