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At least 19 recordsLinked to original sources
PubMed2003

Myometrial effects of selective estrogen receptor modulators on estradiol-responsive gene expression are gene and cell-specific.

We examined in vivo effects of selective estrogen receptor modulators (SERMs) 4-OH-tamoxifen (Tam), GW 5638 (GW) and EM-800 (EM) on myometrial gene expression. The uteri of ovariectomized ewes were infused with 10(-7)M of one SERM via indwelling catheters for 24h preceding hysterectomy. Half of the ewes in each SERM group received an intramuscular injection of 50 microg 17beta-estradiol (E2) 18 h prior to hysterectomy. Northern blot analysis and in situ hybridization demonstrated that E2 increased estrogen receptor (ER), progesterone receptor (PR) and cyclophilin (CYC) gene expression in the cells of both inner layer of myometrium (IM) and outer layer of myometrium (OM) as well as glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression in OM. Tam also increased ER mRNA levels in OM. EM appeared to increase ER gene expression, but antagonized E2's up-regulation of PR and CYC gene expression in both IM and OM. Tam and GW also antagonized E2 up-regulation of PR gene expression in OM but not IM. No SERM affected GAPDH gene expression with or without E2. Immunohistochemistry indicated that E2 increased nuclear ER and PR protein levels in both IM and OM. EM was unique in up-regulating ER protein levels, opposite to its effects in endometrial cells. All SERMs tested antagonized this increase in PR immunostaining preferentially in OM compared to the IM layer. These results illustrate gene and cell layer-specific effects of SERMs in sheep myometrium.

Animals↗
PubMed1987

Endometrial and myometrial effects of progesterone antagonists in pregnant guinea pigs.

Three antiprogestogens of the RU 38.486, ZK 98.734, and ZK 98.299, were studied at different stages of pregnancy in the guinea pig. Treatment starting on postconception day 4 completely prevented nidation; all three compounds had comparable inhibitory potency. Treatment after nidation, starting on postconception day 8, induced decidual collapse and bleeding, but embryonic tissue was retained in nidation sites. In contrast to results in animals in nonfertile cycles, luteolysis was not induced, indicating that antiprogestogens lack the ability to induce uterine prostaglandin synthesis/liberation. On postconception day 43, RU 38.486 showed marginal abortifacient activity. The other compounds induced expulsion more rapidly and at a higher rate. The comparatively pronounced antiglucocorticoid activity of RU 38.486 may account for this difference. With RU 38.486, a high level of uterine prostaglandin sensitivity and a cervical ripening were induced consistently and fast; spontaneous labor, on the other hand, occurred after several days, if at all. Complete uterine evacuation was induced within hours by otherwise inactive doses of sulprostone in various combinations with ZK 98.299 RU 38.486 but surprisingly not with ZK 98.734. A single dose of ZK 98.299 induced an approximately thirtyfold increase in uterine prostaglandin sensitivity within 24 hours, exceeding that present before term, but did not induce spontaneous labor. This is evidence that endogenous prostaglandins were not activated, analogous to perinidation stages. Observation of antiluteolytic activity of antiprogestogens in nonpregnant animals is considered of major theoretical importance in this context. It seems that inhibition of progesterone leads to suppressed uterine prostaglandin liberation. The same effect in pregnancy could explain the inability of the uterus to expel a seriously compromised conceptus. In conclusion, we suggest that progesterone is a stimulator rather than a depressor of uterine prostaglandins in the late luteal phase and pregnancy. The ability of the conceptus to neutralize this stimulatory action of progesterone is considered to be essential for the rescue of the corpus luteum and uterine motor quiescence in the guinea pig. The clinical significance of these findings is that the high frequency of incomplete abortions and protracted, sometimes heavy bleeding in pregnant women treated with RU 38.486 may reflect decidual compromise and simultaneous uterine prostaglandin deficiency, as found in our animal model after progesterone blockage.

Abortion, Induced↗
PubMed2006

A novel selective progesterone receptor modulator asoprisnil activates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated signaling pathway in cultured human uterine leiomyoma cells in the absence of comparable effects on myometrial cells.

CONTEXT: We previously demonstrated that asoprisnil, a selective progesterone receptor modulator, induces apoptosis of cultured uterine leiomyoma cells. This study was conducted to evaluate whether asoprisnil activates TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptotic pathway in cultured uterine leiomyoma and matching myometrial cells. OBJECTIVE AND METHODS: After subculture in phenol red-free DMEM supplemented with 10% fetal bovine serum for 120 h, cultured cells were stepped down to serum-free conditions for 24 h in the absence or presence of graded concentrations of asoprisnil. The levels of TRAIL signaling molecules and cellular inhibitors of apoptosis protein were assessed by Western blot analysis. RESULTS: TRAIL contents in untreated cultured leiomyoma cells were significantly (P < 0.01) lower compared with those in untreated cultured myometrial cells. There was no difference in death receptor (DR)4 and DR5 contents between the two types of cells. Asoprisnil treatment significantly (P < 0.05) increased TRAIL, DR4, and DR5 contents in cultured leiomyoma cells in a dose-dependent manner with a cleavage of caspase-8, -7, and -3, and decreased X-linked chromosome-linked inhibitor of apoptosis protein contents. In cultured myometrial cells, however, asoprisnil treatment did not affect either TRAIL signaling molecule or cellular inhibitors of apoptosis protein contents. The concomitant treatment with 100 ng/ml P4 significantly (P < 0.05) reversed asoprisnil-induced increase in DR4 and cleaved poly(adenosine 5'-diphosphate-ribose) polymerase contents in cultured leiomyoma cells. CONCLUSIONS: These results suggest that asoprisnil induces apoptosis of cultured leiomyoma cells by activating TRAIL-mediated apoptotic pathway and down-regulating X-linked chromosome-linked inhibitor of apoptosis protein levels in the absence of comparable effects on myometrial cells.

Adult↗
PubMed1984

Evolution of cAMP phosphodiesterase activity in cultured myometrial cells: effects of steroids and of successive subcultures.

Cyclic AMP phosphodiesterase (PDE) activity was characterized in culture of ewe myometrial cells and its sensitivity to steroid hormones was tested. Cultured myometrial cells were maintained from the first to the 20th subculture in the presence of 2% of serum in a medium supplemented with 1 microM of insulin. It was found that myometrial cells possess a PDE activity with atypical kinetics. The nonlinear responses in Lineweaver-Burke plots suggest the presence of high- and low-affinity PDE activities. In cell culture, apparent Km values were similar to those obtained from the original myometrium. Vmax values increased with successive subcultures, revealing an increase in the capacity of the cells to degrade cAMP; in parallel, the growth rate decreased. The PDE specific activity in cultured myometrial cells was inhibited by estradiol or progesterone. When added together, no synergistic effect was obtained. The rate of inhibition for both steroids was constant during successive passages for both low- and high-affinity conditions. Results obtained in myometrial cell long-term culture were compatible with reports in other species in vivo. Considering the role of cAMP in the regulation of uterine functions, subcultured myometrial cells provided us a useful experimental system with which to study the cAMP metabolism process.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Prostaglandin-induced luteolysis in pregnant and pseudopregnant rabbits and the resultant effects on the myometrial activity.

The effect of prostaglandin (PG)-induced luteolysis on the myometrial activity in 20--21-day-pregnant and 11--12-day-pseudopregnant rabbits was studied by intrauterine pressure (IUP) recording during PG infusions. The same dose of PG (10 micrograms/h during 8h) was also given to 7 non-pregnant (untreated) does that were used as controls. Peripheral plasma concentration of progesterone and oestradiol-17 beta were measured at 2-h intervals during the infusion. Plasma progesterone level decreased significantly within 2 h or the start of infusion in pregnant and pseudopregnant does and continued to decrease; at the end of 8 h, the concentrations were 31 and 41%, respectively, of the pre-infusion levels. The amplitude of uterine contractions increased significantly after 4 h in pseudopregnant does, increased slightly but insignificantly in the pregnant does and showed no significant change in the non-pregnant does during PG infusion. The amplitudes developed in the pregnant and pseudopregnant does were significantly different. The direct effect of progesterone (1--3 micrograms/h during 4 h) was also studied in 7 non-pregnant rabbits. After 2 h the amplitude of contractions had decreased markedly and the pattern of activity had become irregular. The results support the concept of a myometrial inhibitory factor other than progesterone in rabbit pregnancy and suggest that this factor(s) originates in conceptus.

Animals↗
PubMed1999

Nitric oxide-mediated effects on myometrial contractility at term during prelabor and labor.

OBJECTIVE: To assess the existence of a nitric oxide (NO) system in the human myometrium and the effects of mediators of this system on contractile activity in vitro. METHODS: Myometrial tissue was obtained before the onset of labor and during labor at term. Production of NO was assessed by the use of nicotinamide dinucleotide phosphate diaphorase staining and by immunoblots for NO. Effects of NO were examined by adding L-arginine (the substrate for NO synthesis); N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase); two NO donors, sodium nitroprusside and spermine NONOate; as well as 8-bromo cyclic guanosine monophosphate (8-bromo cGMP) (a second messenger analogue) to organ baths. RESULTS: Myometrial NO production was indicated by positive nicotinamide adenine dinucleotide phosphate diaphorase staining. Immunoblots detected endothelial NO synthase, whereas only a weak signal for inducible NO synthase was seen. The addition of L-arginine (10(-4)-10(-3) mol/L) did not result in any change of contractility. N(G)-nitro-L-arginine methyl ester (10(-3) mol/L) caused a minor increase of contractility in half of the specimens. Sodium nitroprusside, spermine NONOate, and 8-bromo cGMP resulted in a concentration-dependent inhibition of contractility (10(-7)-10(-6) mol/L for sodium nitroprusside, 10(-6)-10(-5) mol/L for spermine NONOate, and 10(-5)-10(-3) mol/L for 8-bromo cGMP). However, at 10(-5)-10(-4) mol/L, sodium nitroprusside exhibited a dose-dependent increase in the frequency of contractions. Women in prelabor did not differ from those in active labor. CONCLUSION: The myometrium produces NO at term. Nitric oxide inhibits myometrial contractile activity. The responsiveness to NO is similar in nonlaboring and laboring women.

Adult↗
PubMed2006

A novel selective progesterone receptor modulator asoprisnil (J867) inhibits proliferation and induces apoptosis in cultured human uterine leiomyoma cells in the absence of comparable effects on myometrial cells.

CONTEXT: Asoprisnil, a selective progesterone (P4) receptor (PR) modulator (SPRM) with mixed P4 agonist/antagonist activities, reduces uterine leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. The evidence from clinical studies suggests that asoprisnil may directly target the uterine leiomyomata. OBJECTIVE AND METHODS: The present study evaluated the effects of asoprisnil on cell proliferation, the expression of apoptosis-related proteins, and apoptosis in cultured human uterine leiomyoma cells and matched normal myometrial cells. PR-A and PR-B expression in the two types of cells was comparatively evaluated. Cell proliferation, proliferating cell nuclear antigen (PCNA)-positive rate, and TUNEL-positive rate were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, immunocytochemistry, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay, respectively. The expression of apoptosis-related proteins and PR was assessed by Western blot analysis. RESULTS: Compared with untreated cultures, asoprisnil decreased the number of viable cultured cells, the PCNA-positive rate, and PCNA protein expression in cultured leiomyoma cells. Asoprisnil increased the TUNEL-positive rate, cleaved caspase-3, and cleaved poly(adenosine 5'-diphosphate-ribose) polymerase expression and decreased Bcl-2 protein expression in cultured leiomyoma cells. These effects were dose and time dependent. In cultured myometrial cells, however, asoprisnil did not affect cell proliferation and apoptosis. PR-B expression was elevated in cultured leiomyoma cells compared with cultured myometrial cells, whereas no differences in PR-A expression were noted between the two cell types. CONCLUSIONS: These results show that asoprisnil inhibits proliferation and induces apoptosis in cultured uterine leiomyoma cells in the absence of comparable effects on cultured normal myometrial cells, suggesting a cell type-specific effect.

Apoptosis↗
PubMed1982

17 beta-hydroxysteroid dehydrogenase activity in cultured myometrial cells: effect of serial subcultures.

17 beta-Hydroxysteroid dehydrogenase (17 beta-SDH) activity was studied in culture ovine myometrial cells. After primary culture, cells were routinely subcultured (every 7th day), seeded at 5 x 10(5) cells per dish and grown in a medium with 2% of serum. 17 beta-SDH activity was measured by incubating intact cell monolayers with [3H]-estradiol (5 x 10(-9) M) in serum-free medium. Metabolites were extracted from both cells and medium, and separated by thin-layer chromatography. 17 beta-SDH was expressed as total E1 formed (cells + medium) in fmol/mg of protein as a function of time. 17 beta-SDH has an approximate Km of 5 x 10(-6) M. After 3 min of incubation, all measurable E1 is within the cells; it is progressively released but after 1 h only 40% of E1 is found in the medium. 17 beta-SDH decreases from day 2 to day 8 of each subculture, whereas total proteins increase. Subculture partially restores 17 beta-SDH activity so that it is always higher on day 2 of any subculture than on day 8 of the previous one, however a progressive decline occurs with successive subcultures. This decline parallels the slowing of cell growth and overall protein synthesis and probably reflects cell ageing.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

The effects in myometrial preparations of D2343, a beta 2-adrenoceptor agonist possessing alpha 1-receptor blocking qualities.

D2343 is a compound with about the same beta 2-adrenoceptor-agonist effect as terbutaline and exhibiting in addition an alpha 1-receptor inhibitory activity. D2343 has been compared to the beta 2-agonist terbutaline on oestrogenized uterine preparations from rat and rabbit (in vitro and in vivo) and in myometrial strips from homo. Generally, D2343 has shown an ability to relax the uterine muscles to the same degree as terbutaline or even more, especially when the two drugs were compared in vitro in preparations from rabbit and rat.

Adrenergic alpha-Antagonists↗
PubMed1987

Enhanced prostaglandin synthesis in the parturient rat uterus and its effects on myometrial oxytocin receptor concentrations.

We measure oxytocin (OT) responsiveness and prostaglandins (PGs) synthesis in uteri of 19, 20, 21 and 22-day pregnant and 2-day postpartum rats to determine whether the enhanced OT sensitivity and PG synthesis in the parturient uterus is the result of a higher cyclooxygenase activity. We also investigated the effects of suppression of PG synthesis on OT responsiveness and OT receptor in 22-day and 23-day pregnant rats. PG productions (PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 in microsomal fractions were quantitated by radio- immunoassays (RIAs). OT receptor concentrations were measured in plasma membrane fractions by radioligand-receptor binding assays. Naproxen sodium was used to inhibit endogenous PG synthesis. We found a close temporal relationship between enhanced OT responsiveness and increased uterine PGE2 alpha synthesis, but no significant difference in cyclooxygenase activities among the microsomes prepared from uteri of different gestational ages. Suppression of PG synthesis attenuated OT responsiveness and markedly reduced OT binding sites, from 242 to 78 fmol/mg protein. There was no change in the binding affinity. These findings suggest that PG stimulates OT receptor formation which leads to enhanced OT responsiveness. The increase in PG production is not mediated by a higher cyclooxygenase activity.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

The effect of myometrial contractures on uterine blood flow in the pregnant sheep at 114 to 140 days' gestation measured by the 4-aminoantipyrine equilibrium diffusion technique.

Uterine blood flow, between 114 and 140 days' gestation, measured by the 4-aminoantipyrine equilibrium diffusion technique, was significantly decreased from 1359.1 +/- 84.4 ml X min-1 (mean +/- SE) in the absence of contractures to 1147.4 +/- 71.8 ml X min-1 (mean +/- SE) during a contracture (p less than 0.01). Contractures reduced total uterine blood flow regardless of whether the ewe was standing or lying. These observations are in keeping with the suggestion that changes in total uterine blood flow may be an important mechanism responsible for the previously described temporal relationship between contractures and fetal neurophysiologic function.

Ampyrone↗
PubMed1976

Calcium uptake by myometrial membranes: effect of A 23187, a calcium ionophore.

A subcellular fraction, relatively enriched with plasma membranes, showed an ATP-dependent Ca2+ uptake. The addition of a Ca2+. Other drugs (angiotensin, prostaglandin F2alpha, 5-hydroxytryptamine and cyclic nucleotides) had negligible effects on Ca2+ transport. The preparation appears to transport Ca2+, although binding is negligible.

Adenosine Triphosphate↗
PubMed1984

The effects of myometrial activity on fetal thoracic dimensions and uterine blood flow during late gestation in the sheep.

We wished to investigate mechanisms by which non-labour contractions of the uterus influence fetal sleep states and respiratory activity during late pregnancy. The relationship between the dimensions of the fetal chest and uterine contractions was examined in 5 pregnant sheep. The dorso-ventral dimension at the level of the xiphisternum (3 fetuses) decreased, on average by 4.4-9.4% while increases of 16.6-18.7% were seen in the transverse dimension (4 fetuses). Blood flow in a middle uterine artery was monitored using a Doppler technique in 5 pregnant sheep. Non-labour uterine contractions were accompanied by mean reductions of 6.5-12.7% in blood flow. Postural adjustments by the ewe also influenced uterine blood flow. A mean increase in blood flow of 5.9-12.0% followed a change from standing to lying; standing caused a mean reduction of 5.9-11.8%. We conclude that the influence of uterine contractions on the fetus is likely to be complex, involving distortion of the body and alterations in utero-placental haemodynamics.

Animals↗
PubMed1984

Increased conception rate in dairy cows after early post partum administration of prostaglandin F2 alpha THAM.

Commercial dairy cows were given a routine injection of dinoprost tromethamine (prostaglandin F2 alpha THAM) in the early post partum period. The first service conception rate of 64 cows given a single 25 mg injection of dinoprost during the period 14 to 28 days after calving was 68 per cent, that of 64 untreated controls was 43 per cent. The difference was highly significant at the level P = 0.007. In cows with no blood progesterone and with basal progesterone concentrations at the time of treatment, indicating absence of an active corpus luteum, the mean conception rates for 30 treated and 38 control cows were 70 and 44 per cent, respectively, demonstrating that this is not a luteolytic effect. Although that implies a positive myometrial effect, the interval from calving to first service was not shortened in treated cows.

Animals↗
PubMed1980

Uterine effects of N-alpha-triglycyl-(8-lysine)-vasopressin and 8-lysine-vasopressin in the first trimester of pregnancy.

Myometrial effects of a vasopressin hormonogen (N-alpha-triglycyl-(8-lysine)-vasopressin, TGLVP) and of 8-lysine-vasopressin (LVP) were studied in early pregnancy. Intrauterine pressure was recorded in 28 women, who were to have a therapeutic abortion at 8-12 weeks of gestation, and intravenous injection of TGLVP (0.5 and 1 mg) or LVP (0.1, 0.2 and 0.4 IU) were given, or control recordings without drug injection were obtained. TGLVP generally caused a biphasic increase in uterine activity with a rise in uterine tone as the most conspicuous initial effect followed by an increase in amplitude and duration of contractions. In the higher dose group the uterine activity remained significantly higher than in the controls during the rest of the recording period of 4-7 h. The magnitude of effect with the two doses of TGLVP did not differ significantly. The initial myometrial response to LVP resembled that to TGLVP but the effects disappeared within 10-45 min. In the controls the uterine activity did not change. It is suggested that vasopressin analogues could have a therapeutic value in the induction of abortion, but further basic studies are required to define this.

Adult↗
PubMed1992

Artificial sapphire contact probes in Nd:YAG endometrial ablation: a quantitative in vitro and in vivo study.

Artificial sapphire contact probes offer theoretical advantages in Nd:YAG endometrial ablation. To examine this, an in vitro and in vivo study of laser-tissue interaction was performed. In vitro, a linear correlation was found between applied energy and total depth of effect, that is, photovaporization and photocoagulation. Using a Round (MTR 1.5) contact probe, an applied energy of 30 joules gave a depth of myometrial effect of 3.3 mm. In vivo, there was a significant reduction in tissue effect (p less than 0.001) compared to in vitro. Difficulty of manipulation of the contact laser probe within the uterus also caused a significant reduction (p less than 0.001) in depth of tissue ablation achieved on the posterior uterine wall compared with that achievable at the uterine fundus, but this may be counteracted by increasing applied energy.

Endometrium↗
PubMed2005

Contractile reactivity of human myometrium in isolated non-pregnant uteri.

BACKGROUND: Perfusion of the isolated uterus has been shown to be a feasible experimental system for studies of the human endometrium and myometrium. Utilizing our established experimental perfusion model we perfused 20 uteri for 27 h and investigated the contractile reactivity of the myometrium in response to 17beta-estradiol (E2) and oxytocin (OT). METHODS: Uteri of group A (n = 4) were stimulated with OT; group B (n = 4) was treated continuously with E2; group C (n = 4) received both E2 and OT for 27 h; group D (n = 4) was perfused for 27 h with E2 with the addition of OT for the last 3 h of the experiment; group E (n = 4) as control group remained without any treatment. The pressure and duration of uterine contractions were recorded during the entire perfusion period using intramural and endoluminal pressure catheters. RESULTS: Compared to the other treatment groups and controls, the most effective myometrial activity was achieved in group D during the OT stimulation period. No relevant myometrial activity was detected in the control group. CONCLUSIONS: Continuous E2 treatment, with the addition of OT for the last 3 h of the 27 h perfusion period, led to the most pronounced uterotonic effects in the presented experimental condition.

Estradiol↗