Regulation of myometrial beta 2-adrenergic receptors by progesterone and estradiol-17 beta in late pregnant rats

Rat myometrium exhibited a marked decrease in the concentration of beta 2-adrenergic receptors immediately before parturition, i.e., in the last 6 h of pregnancy. This phenomenon continued until the withdrawal of myometrial progesterone (-94% from Day 18 of pregnancy to term) and coincided with the sharp increase (+200%) of the myometrial concentration of estradiol. A linear positive correlation was found (r2 = 0.645) between the concentration of beta 2-adrenergic receptors and the log ratio of myometrial concentration of progesterone/myometrial concentration of estradiol (P/E2), suggesting a modulation of beta 2-adrenergic receptors by steroids. In rats with estrogen-dominated uteri (intact of ovariectomized late pregnant rats injected with estradiol), there was no change either in concentration or affinity of beta 2-adrenergic receptors relative to untreated control pregnant rats. In contrast, rats with progesterone-dominated uteri (intact or ovariectomized late pregnant rats treated with progesterone or ovariectomized rats) have an increased number of beta 2-adrenergic receptors, with a decreased affinity of these receptors compared to untreated control pregnant rats or to estrogen-treated rats. These results suggest that progesterone regulates the number of beta 2-adrenergic receptors in myometrium of late pregnant rats. The mechanisms by which progesterone exerts this regulation remains to be elucidated.     

Role of the nongravid part of the uterus in the luteolytic effects of estrogen in pregnant rats

Effects of a low dose of estradiol on the luteal function were studied in intact pregnant rats. The pregnant rats received daily sc injections of 0.1 microgram estradiol or sesame oil from day 7 to 14 of pregnancy (day 1 = day of insemination). Serum progesterone levels on day 15 were significantly lower in the estrogen-treated group than in the oil-treated group. In order to study how estrogen induced luteolysis, the pregnant rats received each of the following treatments on day 7 of pregnancy: (1) The uterus except that containing a single conceptus was removed by hysterectomy (hysterectomy group); (2) All but a single conceptus were removed by aspiration, so that rats carried only a single conceptus with the whole part of the nongravid uterus (aspiration group). Each group of rats received also sc injections of 0.1 microgram estradiol or sesame oil from day 7 to 14 of pregnancy. Estradiol treatment caused a significant decline in serum progesterone levels in the aspiration group on day 15, but this was not the case in the hysterectomy group. There was no significant difference in serum LH levels among any of the groups on day 15 of pregnancy. These results indicated that estradiol induced luteolysis in the intact pregnant rats, which would, at least in part, be mediated through the uterus.     

The influence of estradiol on cholesterol processing by the corpus luteum

Recent studies from our laboratory have suggested that estradiol or androgen precursor may stimulate steroidogenesis in the luteal cell by modulating intracellular cholesterol metabolism including mobilization of cholesteryl esters, stimulation of lipoprotein receptor activity and induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity. To test the functionality of cholesteryl ester turnover per se, we measured the activities of acyl CoA:cholesterol acyltransferase (ACAT) and cholesteryl esterase, the enzymes involved in cholesteryl ester synthesis and hydrolysis, respectively; we also measured de novo synthesis of cholesterol, cholesteryl esters, and steroids. Pregnant rats, hypophysectomized and hysterectomized on Day 12, were treated for 72 h with either estradiol or testosterone, and luteal microsomal and cytosolic fractions were utilized to measure ACAT and cholesteryl esterase activity, respectively. Intact corpora luteal were employed for [14C]acetate incorporation experiments. Basal ACAT activity (expressed as pmol.min-1.CL-1 increased from a mean of 78 +/- 16 in vehicle-treated rats to 119 +/- 18 and 197 +/- 16 in the estradiol- and testosterone-treated rats, respectively. Similarly, total ACAT activity (measured in the presence of exogenous cholesterol) was also increased in estradiol- and testosterone-treated groups. On the other hand, cholesterol esterase activity (expressed either pmol.min-1.CL-1 or pmol.min-1.mg protein-1) was similar in all three groups and comparable to corpora lutea from intact pregnant rats. Hypophysectomy and hysterectomy caused a 50-60% reduction in [14C]acetate incorporation into sterols when compared with intact pregnant rat. Treatment with either estradiol or testosterone not only restored the cholesterol biosynthetic capacity but also enhanced the overall rate of [14C]acetate incorporation into steroids as compared to intact pregnant rats. The major (-80%), newly synthesized steroid was identified as progesterone. In conclusion, the present studies suggest that the major function of luteal estradiol is to induce de novo cholesterol biosynthesis, regulate ACAT activity, and channel available free cholesterol (derived from both endogenous and exogenous sources) for steroidogenesis.     

A physiological dose of estradiol with progesterone affects striatum biogenic amines

The acute effect of estradiol and progesterone on dopamine and serotonin metabolism in rat striatum was studied. One subcutaneous injection of 17 beta-estradiol (300 ng) and progesterone (150 micrograms) into intact male rats increased plasma levels of these steroids, while testosterone, corticosterone, and estrone remained unchanged. Dehydroepiandrosterone, androstane-3 beta, 17 beta-diol and dihydrotestosterone remained undetectably low. Prolactin decreased and androstane-3 alpha, 17 beta-diol, and 17-OH progesterone increased, but less than estradiol and progesterone. Peak levels of striatal dopamine, dihydroxyphenylacetic acid, and homovanillic acid were observed 15-45 min after steroid injection with a return to control values after 45-60 min, while serotonin and 5-hydroxyindoleacetic acid levels were slightly decreased. An injection of estradiol (70 ng) with progesterone (70 micrograms) to ovariectomized female rats left plasma prolactin levels unchanged, while striatum dopamine and serotonin as well as their metabolite concentrations peaked 15-60 min after steroid injection and returned to control values after 45-75 min. To allow for a better comparison of the action of these steroids, the effect of estradiol or progesterone alone and in combination on the brain of ovariectomized rats was compared in the same experiment. A similar increase in metabolites of dopamine levels was observed after these steroids alone or in combination, while dopamine levels were increased only after progesterone alone or in combination with estradiol. An injection of estradiol or progesterone to ovariectomized rats led to peak steroid concentrations at approximately the same time in the brain and plasma. In addition, plasma and brain steroid levels were significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reactivation of regressing corpora lutea by estradiol in the pregnant rat: dependence on placental lactogen

Previous investigations have clearly demonstrated that estradiol maintains corpus luteum function. However, it is unknown whether estradiol can restimulate progesterone synthesis and/or growth of corpora lutea that have already undergone luteolysis. The present study was designed to determine 1) whether estradiol can reactivate the steroidogenic capacity and/or growth of corpora lutea that are deprived of luteotropic support, 2) whether estradiol affects progesterone metabolism, and 3) whether the action of estradiol is related to levels of rat placental lactogen in the peripheral circulation. Rats were hypophysectomized and hysterectomized on Day 12 of pregnancy and were treated between Days 12 and 15 with either estradiol (100 micrograms/day) or 1-cm testosterone implants. Both treatments are known to maintain luteal concentrations of estradiol at physiological levels. In vivo treatment with either estradiol or testosterone prevented the drop in progesterone production and maintained the concentration of serum progesterone at levels found in intact pregnant rats. This action was not due to an alteration in the rate of metabolism of progesterone to 20 alpha-hydroxyprogesterone, since peripheral serum levels and in vitro production of 20 alpha-hydroxyprogesterone were unaffected by estradiol. When testosterone treatment was started 24 and 48 h after hypophysectomy and hysterectomy, at a time when progesterone production had been markedly reduced and luteal growth had ceased, a restimulation of both progesterone synthesis and luteal growth was observed. However, in all cases the ability of estradiol to stimulate progesterone was finite, and corpora lutea ceased to respond by Day 17, coincident with the time that rat placental lactogen became undetectable in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma protein and blood volume restitution after hemorrhage in conscious pregnant and ovarian steroid-replaced rats

We have previously shown that both plasma protein restitution and plasma volume restitution are significantly enhanced in female rats hemorrhaged during the proestrus phase of the estrous cycle. Estradiol and progesterone levels are markedly elevated during proestrus and also increase during pregnancy. The present studies were therefore designed to determine whether the ability to restore plasma protein and blood volume after hemorrhage is augmented during pregnancy and by chronically elevated estradiol levels. The response to moderate hemorrhage (22-23% blood loss) was evaluated in conscious pregnant rats during early and midgestation and compared with that of virgin female rats studied during metestrus. At 22 h posthemorrhage, plasma volume had increased to greater than basal levels, and blood volume was restored to 93 +/- 1% (metestrus), 91 +/- 2% (early pregnancy), and 98 +/- 2% (midgestation) of control (P > 0.05). Animals hemorrhaged during metestrus or early pregnancy restored the same amount of protein to the plasma as had been removed, whereas those hemorrhaged during midgestation restored nearly 50% more plasma protein than had been removed (P < 0.01). In ovariectomized animals with chronic steroid replacement that maintained plasma progesterone at metestrus levels (15 +/- 2 ng/ml) but raised plasma estradiol to twofold that of midgestation (22 +/- 3 pg/ml), the blood volume and plasma protein restitution responses to hemorrhage did not differ from those of ovariectomized animals with no steroid replacement. In summary, posthemorrhage restoration of plasma protein content is significantly augmented during midgestation, but not during early pregnancy. This augmented response cannot be attributed to chronic elevation of plasma estradiol levels alone.     

Effects of the fetal-placental unit on uterine prostaglandin levels at term in the pregnant rat

Uterine prostaglandins (PGs) increase markedly at term in the pregnant rat. To assess the contribution of the fetal-placental unit (FPU) on uterine tissue and uterine venous blood PG concentrations, each uterine horn of 14 unilaterally pregnant rats at day 21 of pregnancy were compared. In addition, 7 bilaterally pregnant rats were studied. Uterine tissue and uterine venous plasma PGF, PGE, 6-Keto-PGF1 (6KF) and thromboxane B2 (TxB2) and systemic plasma progesterone, estradiol and estrone were determined by radioimmunoassay. Uterine concentrations of PGs (ng/mg DNA) were always greater on the pregnant side of unilaterally pregnant rats (p less than .05) although the PGF levels were elevated to a lesser extent than were PGE, TxB2 or 6KF. However, no differences were detected between uterine tissue from the pregnant side of unilaterally pregnant compared to bilaterally pregnant rats. In addition, no differences were found in uterine venous plasma PGs adjacent or opposite the pregnant uterine horn and in systemic plasma progesterone, estradiol and estrone levels in unilaterally vs bilaterally pregnant rats. These data suggest that the presence of the FPU is associated with an increased capacity of uterine tissue to produce PGE, TxB2 and 6KF, and to a lesser degree PGF, and thus may contribute to the increase in uterine PGs periparturition.     

Neutralization of pregnancy-preventing activity of cabergoline, a dopamine agonist with progesterone

Cabergoline (Cab), a dopamine agonist, inhibits the production and/or release of prolactin and reduces progesterone biosynthesis. Cab at doses of 20 microg/kg/d and higher administered on Days 1, 2 and 3 of pregnancy prevented implantation of fertilized ova in all treated female rats. The pregnancy-preventing activity of Cab is attributed to a deficiency of progesterone since estradiol levels remain unchanged. To validate the hypothesis that progesterone deficiency is the cause of the infertility, exogenous progesterone was administered to Cab-treated pregnant female rats and their fertility assessed. Progesterone at a dose of 5 mg/kg/d sc was administered on Days 1 to 7 of pregnancy to female rats treated with Cab (20 and 60 microg/kg/d) on Days 1, 2 and 3 of pregnancy. All progesterone-treated animals became pregnant, and all mated female rats treated with Cab (60 microg/kg/d) and progesterone (5 mg/kg/d) on Days 1 to 7 inclusive became pregnant. In conclusion, progesterone can neutralize the pregnancy preventing activity of Cab. Pregnant female rats treated with Cab can be used to assay for progestagenic activity of compounds.     

Induction of daily PRL surges in rats by chronic treatment with progesterone

The effect of a high plasma progesterone level on the PRL releasing mechanism was investigated in rats of both sexes. Progesterone levels were maintained by implanting silicone tubes filled with the steroid. In the intact female, 6 progesterone tubes (inner diameter 2 mm; outer diameter 3 mm; length 40 mm) were implanted subcutaneously on the estrous day. With 2- to 5- day latent periods, the daily rise in the plasma PRL level was observed coincident with the time of nocturnal surge in the pseudopregnant rats induced by cervical stimulation. The same treatment applied to ovariectomized rats induced by cervical stimulation. The same treatment applied to ovariectomized rats induced diurnal and nocturnal surges. The peak height was lower in ovariectomized rats than that in intact or normal pseudopregnant rats, and was restored to almost the normal range by concomitant implantation of estradiol with progesterone. This latter protocol, however, did not induce any PRL surge in chronically orchidectomized rats. These results suggest that chronically elevated progesterone levels can induce such PRL surges as are observed in pseudopregnant rats, estradiol enhances the magnitude of the PRL surge, and the progesterone sensitive central mechanism, controlling the PRL surge, does not exist in adult male rats.     

Estradiol is responsible for reduced renal prostaglandin dehydrogenase activity in female rats

The contribution of sex steroids to sex-related differences in renal prostaglandin dehydrogenase activity and urinary prostaglandin excretion was examined in 7-8-week-old male and female rats subjected to sham-operation or gonadectomy at 3 weeks of age. Rats were injected subcutaneously twice over a 6-day interval with vehicle (peanut oil, 0.5 mg/kg) or with depot forms of testosterone (10 mg/kg), estradiol (0.1 mg/kg), progesterone (5 mg/kg), or with estradiol and progesterone combined (0.1 and 5 mg/kg). After the second injection, 24-h urine samples were collected for prostaglandin measurement by radioimmunoassay; the rats were killed, and renal and pulmonary prostaglandin dehydrogenase activities were determined by radiochemical assay. Renal prostaglandin dehydrogenase activity was 10-times higher in intact male rats than in intact females. Gonadectomy increased renal prostaglandin dehydrogenase activity 4-fold in females, but had no effect in males; estradiol, alone or combined with progesterone, markedly suppressed renal prostaglandin dehydrogenase activity in both sexes, while testosterone or progesterone alone had no effect. Pulmonary prostaglandin dehydrogenase did not differ between the sexes and was unaffected by gonadectomy or sex-steroid treatment. Intact female sham-operated rats excreted 70-100% more prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in urine than did males; gonadectomy abolished the difference in urinary prostaglandin E2 excretion. Estradiol decreased urinary prostaglandin E2 in females but not in males; treatment with other sex steroids did not alter urinary prostaglandin excretion.     

Effects of the fetal-placental unit on uterine prostaglandin levels at term in the pregnant rat

Uterine prostaglandins (PGs) increase markedly at term in the pregnant rat. To assess the contribution of the fetal-placental unit (FUP) on uterine tissue and uterine venous blood PG concentrations, each uterine horn of 14 unilaterally pregnant rats at day 21 of pregnancy were compared. In addition, 7 bilaterally pregnant rats were studied. Uterine tissue and uterine venous plasma PGF, PGE, 6-Keto-PGF₁ (6KF) and thromboxane B₂ (TxB₂) and systematic plasma progesterone, estradiol and estrone were determined by radioimmunoassay. Uterine concentrations of PGs (ng/mg DNA) were always greater on the pregnant side of unilaterally pregnant rats (p<.05) although the PGF levels were elevated to a lesser extent than were PGE, TxB₂ or 6KF. However, no differences were detected between uterine tissue from the pregnant side of unilaterally pregnant compared to bilaterally pregnant rats. In addition, no differences were found in uterine venous plasma PGs adjacent or opposite the pregnant uterine horn and in systematic plasma progesterone, estradiol and estrone levels in unilaterally vs bilaterally pregnant rats. These data suggest that the presence of the FPU is associated with an increased capacity of uterine tissue to produce PGE, TxB₂ and 6KF, and to a lesser degree PGF, and thus may contribute to the increase in uterine PGs periparturition.     

Ovum transport in pregnant rats is little affected by RU486 and exogenous progesterone as compared to cycling rats

In cycling and pregnant rats, the eggs stay in the oviduct for approximately 66 and 90 h, respectively. The influence of progesterone in these timings was investigated. An excess or a simulated deficit of progesterone was induced with exogenous progesterone or the antiprogesterone RU486, respectively, beginning on the day of ovulation. The effect of these treatments on egg transport in cycling and pregnant rats was assessed in detail and complemented with determinations of estradiol and progesterone circulating levels and progesterone receptor levels in the oviduct. Accelerated transport of ova followed treatment with RU486 in cycling and pregnant rats but with different features. In cycling rats, acceleration began 24 h after the onset of treatment and was not associated with changes in estradiol levels; in pregnant rats, it started 72 h after treatment and was associated with a 5-fold increase in estradiol circulating levels. Thus, RU486 failed to accelerate ovum transport during the first three days of treatment in pregnant rats, in spite of the fact that no progesterone receptors were available in the oviduct as early as 24 h of treatment. Progesterone administration caused egg retention in the oviducts and a 50% reduction in circulating estradiol levels in cycling rats, whereas in pregnant rats progesterone excess did not change estradiol circulating levels and had no effect on the location of embryos on Days 4 and 5. These results demonstrate a different physiological importance of endogenous progesterone in slowing down oviductal ovum transport in cycling and pregnant rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gossypol in female fertility control: ovum implantation and early pregnancy inhibited in rats

Intramuscular administration of gossypol to normally cycling female rats induced an irregularity of the cyclic pattern for as long as the treatment was continued. Furthermore, administration of gossypol from days 0 (day of sperm-positive vaginal smear) to 8 of pregnancy prevented the normal maintenance of pregnancy. Serum values of progesterone and estradiol 17 beta in gossypol-treated normally cycling and pregnant rats were significantly lower than the control levels. The supplement of a combination of exogenous progesterone and estradiol 17 beta eliminated the inhibitory effects of gossypol on ovum implantation and the maintenance of pregnancy. Our results indicate that gossypol may have some usefulness in female fertility control.     

Spatial working memory and hippocampal size across pregnancy in rats

The present experiments investigated the effects of pregnancy on performance in the Morris water maze and on hippocampal volume. In the first study, pregnant rats (in between the first and second trimester) outperformed nonpregnant rats on the Morris water maze on 1 day of testing. In the second study, rats were tested in a working memory variation of the maze in which the spatial location of the platform varied. Pregnant females traveled shorter distances than nonpregnant females during the first two trimesters, but performed worse than nonpregnant females during the third trimester. Latency measures showed a similar profile. Group differences in performance were not related to changes in swim speed. However, changes in performance in pregnant females may be related to estrogen, progesterone, and/or corticosterone levels during pregnancy, with low levels of estradiol and high levels of progesterone being associated with better performance. There were no significant differences between pregnant and nonpregnant animals on any of the brain measures, although pregnant animals tended to have a smaller hippocampus than nonpregnant animals. These results indicate that pregnancy can affect performance, possibly related to the hormonal changes that accompany pregnancy.     

The relationship between ovarian steroids and uterine estrogen receptors during late pregnancy

Although a direct interdependence exists between the ovarian steroids, estrogen and progesterone, the exact role of these two hormones during pregnancy, especially late pregnancy, is not completely understood. Investigations have been conducted to determine whether the circulating levels of progesterone and estrogen or changes in the ratio of progesterone/estrogen in relation to the concentration of uterine estrogen receptors are associated with triggering parturition. Ninety-day old female rats were sacrificed at gestation days 14, 16, 18, 20 and two days post-partum. The plasma levels of estradiol and progesterone were measured by solid-phase radioimmunoassay. Uterine cytosol was subjected to a charcoal binding assay to determine the concentration of estrogen receptors. Our findings demonstrate that there is a significant (p less than 0.05) drop in both plasma progesterone and estradiol during late pregnancy. Also indicated is a significant (p less than 0.05) increase in uterine estrogen receptors throughout late pregnancy. Finally, during this period there is a direct correlation between the shift in the progesterone/estrogen ratio and the increase in the concentration of uterine estrogen receptors in late pregnancy.     

Changes in the binding of angiotensin II to rat placental receptor by estrogen and progesterone

The effects of estradiol and progesterone on the binding of rat placental angiotensin II receptors were examined. Sex steroid (progesterone estradiol plus progesterone) decreased the total number of rat placental angiotensin II receptors, while sex steroid (estradiol plus progesterone) increased angiotensin levels. Our present results suggest that sex steroids may play an important role in the control of the number of the angiotensin binding sites during pregnancy.     

A prenatal source for defeminization of female rats is the maternal ovary

Sexual behavior in laboratory rats is influenced by a variety of factors in the perinatal environment. Male rats are masculinized and defeminized in response to circulating testosterone perinatally. Females undergo a process of feminization but in some cases are exposed to testosterone. Previous work has shown that during prenatal development female rats normally undergo a partial masculinization and defeminization of sexual behavior as reflected by altered responsiveness to gonadal hormones in adulthood. In the present study we investigated whether the maternal ovary influences adult females' responsiveness to gonadal hormones. Pregnant rats were ovariectomized on Day 10 of pregnancy and their offspring tested for sexual behavior in adulthood. Following ovariectomy pregnancies were maintained by administration of systemic progesterone. In addition the ovariectomized pregnant rats were given one of three daily treatments (Days 10-21): 0.2 microgram estradiol benzoate in sesame oil and 0.1 cc propylene glycol, 5 mg of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) in 0.1 cc propylene glycol, or 0.1 cc propylene glycol. A control group was generated from SHAM operated mothers given daily control injections of propylene glycol and sesame oil. Offspring were ovariectomized in adulthood and tested for display of feminine sexual behavior in response to estradiol benzoate and progesterone or estradiol benzoate alone. Masculine sexual behavior was measured in response to testosterone propionate (TP). Feminine sexual behavior was enhanced in offspring from ovariectomized mothers given only progesterone replacement during pregnancy. Offspring from mothers treated with ATD displayed the greatest elevations in feminine sexual behavior. Estradiol treatments of ovariectomized mothers prevented the increase in feminine potential seen in offspring in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of progesterone on follicular growth in the rabbit ovary

Studies were undertaken to measure the growth of follicles in the rabbit ovary during periods of elevated blood levels of progesterone. The progestin was increased in the blood by pregnancy or by implantation of progesterone pellets, which raised blood progesterone to near the levels measured during pregnancy. After 1, 2, 3, or 4 weeks of pregnancy or progesterone-pellet treatment, follicles of 1.0 mm external diameter or greater were dissected out of the ovaries and their external diameters were measured; then, each follicle was extracted for measurement of estradiol content. Blood levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in these animals as well. Follicles up to 2.5 mm in diameter were found in the ovaries of nonpregnant and untreated animals while 1.8 mm was the maximal size found during pregnancy or progesterone-pellet treatment. Furthermore, both in pregnant and in progesterone-treated rabbits, the follicular estradiol content and concentration were significantly suppressed compared to follicles from untreated rabbits. The progesterone pellets had no major effect on the levels of LH and FSH in the blood; the concentration of these gonadotropins in the progesterone-treated rabbits was virtually identical to levels previously measured in the blood of pregnant animals. The results of these studies indicate that progesterone exerts an inhibitory action on follicular development and steroidogenic function in the rabbit ovary. The progesterone action appears to be exerted directly on the ovary and is not indirect, by way of an inhibition of gonadotropin secretion.     

Effect of indomethacin, cycloheximide, and aminoglutethimide on ovarian steroid and prostanoid levels during ovulation in the gonadotropin-primed immature rat

It has become popular to use the gonadotropin-primed immature rat to study ovulation. The ovarian content of progesterone, estradiol, PGE2, PGF2 alpha, and 6-keto-PGF1 alpha during the ovulatory process was determined in this model. Also, the effect of three anti-ovulatory agents on the ovarian levels of the above substances was determined. At 23 days of age, Wistar rats were primed with pregnant mares serum gonadotropin (PMSG) sc, and two days later the ovulatory process was initiated with human chorionic gonadotropin (hCG) sc. The ovarian follicles began rupturing 12 h later. Ovaries were assayed for the two steroids and prostanoids at 2-h intervals before and several 4-h intervals after ovulation. The ovarian estradiol level increased slightly between 0 and 2 h after hCG, while the progesterone level increased sharply between 2 and 4 h after hCG--at a time when the estradiol declined markedly. All three prostanoids increased concomitantly with progesterone. When the PG synthesis was blocked by indomethacin treatment at 1 h before hCG, ovarian progesterone levels still increased. In contrast, when steroidogenic activity was inhibited by aminoglutethimide, the ovarian prostanoid levels also decreased. Cycloheximide had little effect on the steroids and prostanoids. It is concluded that ovarian prostanoid synthesis might be influenced by ovarian steroid output.     

Prevention of implantation by [D-Trp6-LH-RH in the rat: comparative study with the effects of large doses of HCG on pregnancy.

Effect of large doses of [D-Trp6]-LH-RH and HCG on implantation of fertilized ova was examined in the rat. Subcutaneous administration of 6ug[D-Trp6]-LH-RH per day from days 1 to 5 of pregnancy by an implanted minipump completely prevented the implantation of fertilized ova associated with a dramatic reduction of plasma progesterone on days 4 and 8, with a slight reduction of estradiol on day 4. There was no balooning of the uterus in the exploratory laparatomy on days 8 and 14. Administration of 1000 U of HCG daily from days 1 to 5 partially prevented implantation and completely terminated gestation. However, plasma progesterone and estradiol levels did not differ from those in the control animals. Ovaries in the [D-Trp6]-LH-RH treated rats appeared to be the same in size as those of the control pregnant rats, whereas the ovaries of the HCG-treated rats were hypertrophied. The results suggest that [D-Trp6]-LH-RH prevents nidation through a mechanism different from that for the adverse effect of excess of HCG on pregnancy.