Inhibition of progesterone synthesis in placenta by administration of dexamethasone to pregnant rats

Glucocorticoid receptors have been detected in placenta from several species, including the rat, although the biological function of corticoids is unknown in placenta from the latter species. The present experiments examined the effect of glucocorticoid treatment on placental progesterone biosynthesis from endogenous precursors by incubated basal zone trophoblast and labyrinthine zone of placentas from adrenalectomized-ovariectomized rats at the end of pregnancy. It was found that a higher proportion of synthesized progesterone was retained in the tissue than that released into the incubation medium. Treatment of rats on the 17th-18th day of pregnancy with 10 micrograms/ml of dexamethasone in the drinking saline for 3 days, produced a significant inhibition of progesterone detected in tissue and medium of incubated placental zones. In vitro addition of dexamethasone (10(-4) M) was also effective in reducing progesterone in the placental zone studied (LZ). Serum progesterone of intact rats was in the range of rats near parturition (approx 25 ng/ml) and dropped to almost undetectable levels in rats with adrenalectomy and ovariectomy, with or without dexamethasone treatment, suggesting that in late pregnancy the rat placenta does not contribute significantly to circulating levels of progesterone. This glucocorticoid effect could not be extended to estrogens, as we, in accord with the work of other groups, failed to detect estrogen synthesis in rat placenta. It is suggested that a function for glucocorticoid receptors in rat placenta may be the inhibition of local progesterone production.     

Progesterone and estradiol in cat placenta-Biosynthesis and tissue concentration

Ovarian and placental steroids are essential for the maintenance of pregnancy. In some mammals it is evident that the placenta is responsible for the production of steroids. However, in the domestic cat, steroid secretion from the placenta has not yet been elucidated. Our study aimed to find out whether feline placentae are able to produce steroids. Placentae from different pregnancy stages were analyzed for mRNA expression of five steroidogenic enzymes (HSD3B1, CYP11A1, CYP17A1, HSD17B1 and CYP19A1) and for tissue concentrations of progesterone and estradiol. Steroidogenic enzymes responsible for the final steps of estradiol (CYP19A1) and progesterone synthesis (HSD3B) were expressed at very high levels and followed almost the same pattern over pregnancy as the intraplacental hormones themselves. By contrast, the other enzymes were found in very low quantities suggesting that biosynthesis occurs via extra-placental steroid precursors. The plasma steroid profiles measured by other groups differ from the placental hormone courses determined by us; therefore we conclude that the feline placenta can produce progesterone and estradiol.     

Decreased concentrations and affinities of oestrogen and progesterone receptors of intrauterine tissue in human pregnancy

Cytoplasmic and nuclear receptors for oestrogen and progesterone were measured in non-pregnant myometrium and endometrium and compared to concentrations found in decidua of ectopic pregnancy (6-8 weeks gestation) and therapeutic abortions (8-16 weeks). Amnion, chorion, placenta, decidua and myometrium at full term pregnancy were also assayed for the same receptors. High affinity binding was confirmed in the non-pregnant tissue; in early pregnancy, decreases in concentrations of cytoplasmic receptors were demonstrated, these decreases becoming more marked as pregnancy progressed in the 1st trimester. Nuclear receptor concentrations were not significantly different. Significant decreases in the occurrence of positive receptors with the progression of pregnancy were also demonstrated for cytoplasmic and nuclear oestrogen and nuclear progesterone receptors. Tissue at full term pregnancy had no detectable receptors, irrespective of whether the patients were in labour or not. Increasing the range of the labelled steroids failed to demonstrate any low affinity binding sites and pre-assay removal of endogenous hormones also had no effect on receptor status. When endogenous hormones were removed, displaceable binding was demonstrated in the presence of excess unlabelled ligand. However, this binding did not conform with receptor dynamics on Scatchard analysis. Heating the cytosol prior to assay or failure to remove endogenous steroid hormones eliminated this binding. Cytosolic oestrogen and progesterone levels increased significantly in the decidua of therapeutic abortions, whilst term pregnant tissue had the highest concentration of endogenous hormones.     

Steroid hormone metabolism by the chorioallantoic placenta of the mountain spiny lizard Sceloporus jarrovi as a possible mechanism for buffering maternal-fetal hormone exchange

The placenta provides a maternal-fetal exchange interface that maximizes the diffusion of gases, nutrients, and wastes. However, the placenta also may permit diffusion of lipid-soluble steroid hormones that influence processes such as sex-specific fetal development and maternal pregnancy maintenance. In mammals, placental steroid metabolism contributes to regulation of maternal and fetal hormone levels. Such mechanisms may be less highly developed in species that have recently evolved placentation, such as many reptiles. We therefore chose to investigate placental metabolism of steroids in the viviparous lizard Sceloporus jarrovi. In vitro tissue incubations tested the abilities of the chorioallantoic placenta to clear progesterone and corticosterone by converting them to other metabolites and to synthesize progesterone. Placental tissue rapidly cleared progesterone and corticosterone added to the incubation media, indicating that the tissue had converted the steroids to other products. Placental tissue also synthesized substantial concentrations of progesterone from the prohormone pregnenolone. Thus, even in a species with a simple, recently evolved placenta, steroid metabolism appears to be highly developed and could be critical for regulation of maternal and fetal hormone levels. This finding suggests that placental hormone metabolism may be critical to the successful evolution of placentation.     

Antioxidant status of ewe's blood during pregnancy and lactation

Antioxidant status of ewe's blood during pregnancy and lactation was studied. It is revealed that the lipid peroxidation in erythrocytes is decreased, whereas in blood plasma is increased in the middle pregnancy, reaching the maximum shortly before peak of progesterone production. The activities of antioxidant enzymes are increased at the end of pregnancy, when the level of progesterone in blood is maximal. The positive correlation between plasma progesterone level and activity of erythrocyte superoxide dismutase (p < 0.01), between plasma cortisol concentration and total antioxidant capacity of blood plasma (p < 0.05) are revealed. It is shown, that the activities of antioxidant enzymes reach a maximum in the critical periods of pregnancy, providing the protection of the maternal organism and the fetus against negative influence of free radicals. The positive correlation between a level of hormones and separate parameters of antioxidant system in blood allows to assume, that progesterone participates in the regulation of enzymatic part of the antioxidant system, while cortisol is implicated in the regulation of the non-enzymatic component of this system in ewes.     

Serum chorionic gonadotropin,progesterone, and estradiol-17β levels during pregnancy in the common marmoset,Callithrix jacchus

The serum levels of chorionic gonadotropin (LH/CG), progesterone, and estradiol-17β were measured during pregnancy in the common marmoset. The gestation period in five females was 144±1.5 (141–145) days. The LH/CG level increased from the early stage of pregnancy, reached a maximum of 10–17 ng/ml at 50 to 70 days and decreased to under 40 pg/ml at about 100 days. The progesterone level maintained the same value as that at the luteal phase of 20–40 ng/ml until 90 days of pregnancy, when the serum LH/CG was declining, thereafter increased abruptly, reached a maximum of 140–210 ng/ml at 110–130 days and fell to a low level of under 0.4 ng/ml at 5–10 days before parturition. The estradiol-17β was less than 2 ng/ml until 90 days of pregnancy, thereafter increased abruptly and maintained a high level of 40–135 ng/ml until just before parturition. The 3β-hydroxysteroid dehydrogenase activity in the placenta of the common marmoset was 40 times higher than that in the fetal adrenal, while in the Japanese monkey the former was only about one 40th of the latter. The time course of the serum progesterone and estradiol-17β during pregnancy and the role of the placenta which synthesized and secreted these hormones in the common marmoset showed a similarity to those of humans and anthropoid apes rather than those ofMacaca species. The common marmoset represents a valuable animal model for investigating the feto-placental unit in humans.     

哺乳类动物妊娠晚期孕激素撤退的三种机制

内分泌激素是维持妊娠和启动分娩的重要因素。孕激素是静息子宫、维持妊娠的主要激素,而糖皮质激素、前列腺素和雌激素等激素则与分娩启动密切相关。孕激素水平的下降是很多哺乳类动物分娩启动的前提条件,然而有些哺乳类动物包括灵长类在整个妊娠过程包括分娩中均维持着高水平的孕激素,此现象令人费解。越来越多的证据表明,人类分娩启动时孕激素同样出现了撤退,但是发生在孕激素的受体水平,主要表现为孕激素受体亚型表达比值和孕激素受体转录辅助因子表达的改变。本文比较了人类和其它哺乳类动物分娩启动时孕激素撤退的三种模式,即黄体溶解、胎盘P450c17羟化酶上调和孕激素受体功能改变,旨在进一步阐明人类分娩启动机制,从而为防治早产提供新的思路。     

Oxytocic activity of plasma and posterior pituitary lobe after ovariectomy and implantation of stilboestrol or progesterone tablets in female rats

The purpose of this work was to compare the oxytocic activity of plasma and posterior pituitary lobe extract in rats after sham operation, ovariectomy and after subcutaneous implantation of stilboestrol or progesterone tablets in ovariectomized rats. On the 5th day after ovariectomy or implantation of hormones, sample of 2 ml of blood were obtained under urethane anaesthesia from the cephalic end of the right external jugular vein, and the animals were killed by decapitation. The posterior pituitary lobe was removed and homogenized in 0.9% NaCl solution acidified with glacial acetic acid. The oxytocic activity of plasma and extracts of the posterior pituitary lobe was determined by the method of Van Dongen and Hays on fragments of lactating rat mammary tissue. On the 5th day after ovariectomy or implantation of stilboestrol the oxytocic activity was found to be significantly increased in the plasma and posterior pituitary lobe, and after progesterone implantation it was decreased in the posterior pituitary lobe.     

Peripheral blood concentrations of progesterone and oestradiol during human pregnancy and delivery

To evaluate the significance of progesterone and estradiol in human uterine activity during pregnancy and delivery the blood concentrations of these hormones were monitored weekly during the last trimester of pregnancy and at the onset of labour in 15 women, and before and 3 hours after the induction of term delivery in 83 parturients. Neither plasma concentrations of progesterone or estradiol nor the ratio of progesterone to estradiol changed significantly during the last trimester of pregnancy or at the onset of delivery. After the induction of delivery parturients with initial progesterone dominance (ratio of progesterone to estradiol higher than 5 before induction) demonstrated a significant fall in serum concentration of progesterone and in the ratio of progesterone to estradiol while estradiol concentration rose significantly. In estrogen dominant women (progesterone to estradiol ratio equal to or lower than 5) the serum concentration of progesterone and the ratio of progesterone to estradiol rose significantly during the 3 hours after the induction of delivery. Our results suggest that the peripheral blood levels of progesterone and estradiol do not correlate with the tissue biochemical changes which prepare the uterine cervix and myometrium for delivery. The observation that the ratio of progesterone to estradiol decreased in progesterone-dominant and increased in estrogen-dominant women stresses the importance of a well balanced equilibrium of these hormones for prostaglandin metabolism during human delivery.     

Changes in the proportion of free and bound ribosomes in the syncytiotrophoblast of normal human placenta during pregnancy

Samples of normal human placental tissue from the first and second trimester and the end of pregnancy were processed for electron microscopy. The ratio of free to bound ribosomes in the syncytiotrophoblast was determined by the point-counting method in photographs giving a 45,000-fold final magnification. The ratio of free to bound ribosomes was found to be significantly higher at 9-11 weeks than at 6-8 weeks and to be significantly lower at 12-14 weeks than at 9-11 weeks. No significant differences were found between the 12th to 14th week and the 20th to 25th week. These data were compared with the ratio of free to bound ribosomes in different regions of the placenta at the end of pregnancy.     

Free amino acids and some enzymes of placental amino acid metabolism at different stages of its development]

There were revealed changes in the content of free amino acids and in the activity of glutamic dehydrogenase, aspartic- and alanine-aminotransferases in the course of development of the placenta in guinea pigs. The greatest values by the indices under study were reached by the 25th--30th days of pregnancy, i.e. by the period of final formation of the placenta. By the 40th day of pregnancy the activity of the enzymes and the content of free amino acids fell, and from the 45th day persisted at a certain stable level up to the occurrence of labour.     

Study of the fetal and maternal renin-angiotensin system and chorio-placental steroids in the guinea pig]

1.) Total renin, active renin, prorenin, angiotensin II, estradiol and progesterone were measured in maternal, placental and fetal blood and in trophoblastic and uterine tissues of the guinea pig. Furthermore, membrane angiotensin II receptors were measured in trophoblastic tissues. 2.) Blood and tissue concentrations of total renin, active renin, angiotensin II and steroids are shown to increase with gestational age. At the full term of pregnancy (70th post-coital day), tissue concentrations of total renin in chorion (23,900 +/- 2,752 ng/g of tissue/h), maternal placenta (14,210 +/- 1,131), fetal placenta (12,475 +/- 927) and uterus (7,677 +/- 798) are 100 time higher than those observed in placental, fetal and maternal blood. Distribution of blood and tissue prorenin (inactive renin) is similar to that found for total renin. Active renin/Total renin ratio reaches 1% in uterine, placental and chorion tissues and 9.3 +/- 1.0% in maternal, placental and fetal blood. 3.) Angiotensin II levels in systemic maternal blood (690 +/- 99 pg/ml) and in uterine blood (467 +/- 84) are higher than those found in placental blood (266 +/- 39) and in different trophoblastic tissues (between 200 and 400 pg/g). Angiotensin II receptor concentrations are highest in chorion. 4.) Regarding the steroid hormones, it is noted that placental and maternal blood contain more progesterone than trophoblastic tissues. The highest concentrations of estradiol are found in chorion tissue and uterine blood. 5.) A positive correlation is observed between angiotensin II and estradiol in uterine blood (r = 0.69, P less than 0.01) and in chorion (r = 0.71, P less than 0.01). These findings indicate that angiotensin II and estradiol could, by their interactions, play an important role in the physiology of pregnancy.     

Effects of prostaglandins on peripheral progesterone and uterine diamine oxidase in the pregnant hamster

Serum progesterone and uterine levels of diamine oxidase (DAO) activity were determined during pregnancy in hamsters. Progesterone was elevated on Day 1 of pregnancy, had a transient peak on Day 5, remained relatively constant on Days 6–10, and then increased on Days 13 and 14. Uterine DAO activity could not be detected until Day 7 of pregnancy, approximately 1 $\text{1}\text{2}$ days after the initiation of implantation. DAO activity was associated with placental tissue, and more than 90% of the activity was localized in the maternal placenta. The temporal relationship between changes in serum concentrations of progesterone and uterine levels of DAO activity following PG administration also was studied. Serum progesterone was significantly depressed by 6 hr after treatment with PGs on Day 7 of pregnancy. However, uterine levels of DAO activity at 6 hr in the treated animals were not different from those in control animals. In contrast, both the serum progesterone concentrations and uterine levels of DAO activity were significantly lower at 24 hr after PG treatment. The effects of PG treatment on uterine DAO activity were completely blocked by concomitant administration of progesterone. However, concomitant administration of Provera® only blocked the effect of one PG analog that was tested (9-deoxo-9-methylene-16,16-dimethyl0-PGE₂). The data indicate that changes in uterine DAO activity following treatment with the PGs used here are primarily a consequence of a decrease in peripheral progesterone (i.e. a luteolytic effect of the PG).     

Monitoring blood plasma leptin and lactogenic hormones in pregnant sows

The mechanism of action of leptin in pregnant breeding sows, in which hyperphagia is managed through dietary strategies, is yet to be clarified. The aim of this study was to monitor leptin concentrations and their interactions with lactogenic hormones in Large White×Landrace breeding multiparous sows (n=15). All sows showed a normal body condition (mean body condition score: 2.96). Blood samples were collected the day after weaning the litters, at insemination, every 15 days up to day 45 of pregnancy and every 7 days from day 46 to farrowing. At delivery, the placenta was collected for the analysis of leptin and leptin receptor expressions. Plasma leptin levels increased from the end of mid gestation (day 72) and remained high until farrowing (P<0.05). As expected, plasma prolactin (PRL), low during most of pregnancy, increased during the 2 weeks before farrowing (P<0.05), whereas progesterone levels reached plateau at 30 days of gestation and decreased at farrowing (P<0.05). Cortisol levels peaked close to farrowing (P<0.05). Leptin was expressed in the placenta, where the receptor expression analysis showed the presence of the short form but not of the long form. A positive correlation was found between leptin and PRL concentrations during mid (r=0.430; P<0.001) and late (r=0.687; P<0.001) pregnancy, and with progesterone in early pregnancy (r=0.462; P<0.05). During late gestation, a positive correlation was observed between leptin and cortisol (r=0.585; P<0.001). Our results suggested that, in restrictively fed pregnant sows, the leptin levels increased from the end of mid pregnancy to delivery, confirming the presence of leptin resistance. We showed a correlation between leptin and lactogenic hormones during different stages of pregnancy in sows. Lactogenic hormones show pregnancy-specific changes in their secretion and all may become involved in modulating leptin signal.     

Response to gonadotropic stimulation of cultured rat luteal cells isolated from corpora lutea of early pregnancy. Cytochemical and biochemical studies

The hormonal activity of corpora lutea isolated from pregnant rat was examined on 1, 2, 3, 4, 5, 6, 15, and 20th day of pregnancy. The cells were grown as a monolayers up to 6 days at 37 degrees C in Medium 199 supplemented with 10% calf serum. The concentrations of progesterone and estrogens were measured using appropriate radioimmunoassays [1, 7] respectively. Luteal cells were cultured with the addition of the following amounts of hormones: 100 ng LH, 10 i.u. HCG, 100 ng PRL and 150 ng estradiol 17 beta. Cytochemical and histochemical observation of the activity of delta 5, 3 beta-hydroxysteroid dehydrogenase (delta 5, 3 beta-HSD) were also carried out. The addition of LH and HCG to culture medium of cells collected on day 1 and 2 of pregnancy caused increased histochemical reaction for delta 5, 3 beta-HSD and progesterone secretion. It was only on day 3 of pregnancy that the influence of PRL was observed. On day 4 corpus luteum cells began to respond to exogenous estradiol. On day 5 the sensitivity of corpus luteum to exogenous hormones disappeared but the intensive hormonal activity of the corpus luteum marked by the high level of progesterone, was maintained.     

Expression level of ABCG2 in the placenta decreases from the mid stage to the end of gestation

The aim of this study was to elucidate the expression pattern of ABCG2 in the placenta from the mid stage to the end of gestation. rABCG2 expression was investigated in rats on the 14th gestation day (gd) and the 20th gd. Expression of the rABCG2 gene and expression of rABCG2 protein in the placenta were detected on gd 14 by RT-PCR and Western blot analysis respectively. The expression level of rABCG2 on gd 20 was less than that on gd 14. We investigated whether progesterone, secreted from the placenta, regulates the expression of ABCG2 in BeWo cells. Expression levels of the ABCG2 gene and protein in BeWo cells were decreased by progesterone treatment. We conclude that progesterone plays a role in reduction in the expression level of ABCG2 in the placenta with the advance of gestation from the mid stage to the end of gestation.     

Enhancement of α-lactalbumin-like activity in mammary explants from pregnant rats in the absence of exogenous prolactin

Mammary explants from pregnant rats showed a progressive increase in α-lactalbumin activity during culture with insulin, hydrocortisone and prolactin. Unexpectedly, culture with only insulin and hydrocortisone produced a similar rate of increase of α-lactalbumin-like activity, but this increase commenced about 24 hr later. The delay suggests that the enhanced activity effected by insulin and hydrocortisone is not a reflection of carry-over of endogenous mammotrophic hormones. Insulin plus hydrocortisone did not stimulate casein or fatty acid synthesis by pregnancy tissue, and did not enhance α-lactalbumin-like activity in virgin rat mammary explants. Enhancement of this activity by insulin plus hydrocortisone in pregnant tissue was constant over a wide range of glucocorticoid concentrations, but was inhibited by progesterone. Available evidence indicates that the active factor in extracts from insulin-hydrocortisone-explants is a heat-stable protein which is either α-lactalbumin itself, or another molecule with similar specifier properties.     

Patterns of inhibin and FSH localization in endometrium of baboon (Papio anubis) during menstrual cycle and early pregnancy.

Immunoreactive 10.5 KDa moiety of inhibin and hFSH was present in the baboon endometrium during menstrual cycle, early pregnancy and in castrated animals treated with steroid hormones, estrogen and/or progesterone. Endometrial differences during the menstrual cycle altered the intensity of immunostaining of inhibin and FSH. Maximum staining was observed in late luteal phase for both the hormones. In early pregnancy (35th day), the conceptus increased the staining for inhibin in the adjoining endometrial glands. Treatment of castrated animals with steroids for 14 days caused increased staining for inhibin. Maximum staining was observed when treated with estradiol or progesterone, whereas combination of estrogen and progesterone treatment decreased the staining reaction. In conclusion, both inhibin and FSH were localized in baboon endometrium and were under the influence of estrogen and progesterone.