Receptors In Myometrium Research Articles

Title: β3 Adrenergic Receptor Signaling in the Human Myometrium

Preterm labor leading to preterm birth is the leading cause of infant morbidity and mortality. Although β2 adrenergic agonists fail to provide adequate tocolysis, the expression of the β3 adrenergic receptor in myometrium and its unique signaling suggest a role for β3 agonist in the management of preterm labor. Western blot analysis showed that the β3 adrenergic receptor expression increased in human pregnancy myometrium compared to nonpregnant tissues (p < 0.0001). There was no difference in β3 adrenergic receptor expression throughout pregnancy (p > 0.05). The addition of the β3 agonist mirabegron in the tissue bath relaxed oxytocin contracted myometrium with an EC50 of 41.5 µM. Relaxation was partially blocked by the addition of the eNOS blocker Nω-nitro-L-arginine, or the large conductance potassium channel blocker paxilline. Combination of Nω-nitro-L-arginine and paxilline prevented mirabegron-mediated relaxation. Imaging revealed that the β3 adrenergic receptors are expressed by both myocyte and microvascular endothelial cells isolated from human myometrium. Nitric oxide production measured by 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate revealed that mirabegron stimulated nitric oxide production in myometrial endothelial cells. These data suggest that both endothelial and smooth muscle cells contribute to relaxation through disparate signaling pathways. Repurposing of approved medications tested in human myometrium as uterine tocolytics can advance prevention of preterm birth. These data argue that further examination of β3 adrenergic receptor signaling in myometrium may reveal mirabegron as a useful tocolytic in combination tocolysis regimens.

Expression of Cannabinoid Receptors in Myometrium and its Correlation With Dysmenorrhea in Adenomyosis.

The myometrium, especially the junctional zone (JZ), is now well documented to have a role in the pathogenesis of adenomyosis. Cannabinoid receptors have been shown to participate in the establishment of endometriosis and its pain perception. However, its relation to adenomyosis has not been identified yet. The aim of this study was to investigate the expression of cannabinoid receptor type I (CB1) and type II (CB2) in myometrium of uteri with and without adenomyosis and determine the correlation between their levels and clinical parameters of adenomyosis. We collected tissue samples of JZ and the outer myometrium from 45 premenopausal women with adenomyosis and 34 women without adenomyosis. CB1 and CB2 messenger RNA (mRNA) and protein expression levels were evaluated by the use of Western blotting and real-time quantitative polymerase chain reaction from all samples. Clinical information on the severity of dysmenorrhea and other data were collected. We found both CB1 and CB2 mRNA and protein levels in women with adenomyosis were significantly higher than those of controls, and CB1 expression levels in JZ were positively correlated with the severity of dysmenorrhea. These data suggest that cannabinoid receptor CB1 may be involved in the pathogenesis of dysmenorrhea in adenomyosis and may be a potential therapeutic target.

Impact of oestrogen and progesterone receptor expression in the cancer cells and myometrium on survival of patients with endometrial cancer

Loss of oestrogen receptor (ER) and progesterone receptor (PR) expression in endometrial cancer cells indicates poor prognosis. The aim of this study was to determine the correlation of ER and PR expression in cancer cells and the surrounding myometrium with the disease progression. Immunohistochemical expression of ER and PR was detected in cancer and myometrial cells of patients with EC. ER was detected in 65.2% of cancer cells and in 88.4% of myometrial cells. PR was detected in 59.4% of cancer cells and in 84.1% of myometrial cells. The 5-year overall survival (OS) was 76.8%. Patients with ER and PR negative EC had a shorter period until recurrence (p = .013 and .043) and shorter OS (p = .011 and .066) than those with ER and PR positive cancer. Negative ER and PR status in EC has an impact on recurrence and poor OS. The status of hormone receptors in myometrium may be useful in disease prognosis.Impact StatementThe status of hormone receptors in endometrial cancer has been the subject of numerous studies and loss of hormone receptors indicates higher tumor grade and higher clinical stage, lympho-vascular space invasion and deeper myometrial invasion. Although, the communication between the endometrium and myometrium is crucial under physiological conditions, the status of hormone receptors in the myometrium and its significance in cancer progression is poorly studied.Our results showed that loss of ER in the myometrium indicate poor prognosis. The assessment of hormone receptor status in myometrium might be useful in predicting the course of the disease. Results of our research support the theory that stromal and myometrial cells may contribute to tumorigenesis in endometrial cancer.Better understanding of ER/PR expression in myometrial cells is needed, and our research opens new possibilities for identification of key pathways and new potential target molecules in EC prognosis and treatment. It is probable that future classification of endometrial cancer will rely on molecular sub-typing, where the status of hormone receptors in the myometrium might play an important role.

Expression Pattern of G-Protein-Coupled Estrogen Receptor in Myometrium of Uteri with and without Adenomyosis.

Objective To compare the expression of G-protein-coupled estrogen receptor (GPER) in the junctional zone and outer myometrium of the proliferative and secretory phases of women with and without adenomyosis. Methods A total of 76 women were included in this study, 42 with adenomyosis (proliferative phase, n = 23; secretory phases, n = 19) and 34 controls (proliferative phase, n = 16; secretory phases, n = 18). Protein and total RNA were extracted from the junctional zone (JZ) and outer myometrium (OM). GPER protein and mRNA expression levels were evaluated by the use of western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). Results The expression of GPER protein and mRNA in women with adenomyosis was significantly higher than that of control subjects, both in the junctional zone and in the outer myometrium and both in the proliferative and in the secretory phases. Conclusion The significant and consistent increase in GPER expression in adenomyosis compared with control subjects, regardless of whether it was in the proliferative or secretory phases and regardless of whether it was in the JZ or OM, suggests that GPER plays an important role in the pathogenesis of the adenomyosis.

The Preliminary Study About the Involvement of Relaxine in Adverse Effect of Polychlorinated Biphenyls on Bovine Myometrial Contractions

Polychlorinated biphenyls (PCBs) are a group of synthetic xenobiotics, which were used in lots of industrial applications. Two individual congers (PCB 153 and PCB 77) belong to the most prominent environmental contaminations among PCBs, but they have opposite type of configuration and therefore they can exert a different way of action. Since PCBs increased the force of myometrial contractions, in this work, their effect on myometrial sensitivity on inhibitor of myometrial contractions (relaxine, RLX) was studied. Bovine myometrial cells and strips, and luteal cell at 4-8 month of pregnancy, were obtained accidentally in commercial abattoir. They were treated by PCB 153 and PCB 77 and mRNA expression of RLX receptor in myometrial cells and contractions of myometrial strips as well as the secretion of progesterone (P4) and oxytocin (OT) from luteal cells, were measured under their effect. Both studied congeners decreased (P<0.05) the mRNA expression of RLX receptor in myometrium. Admittedly, both PCB 77 and 153 increased (P<0.05) the basal force of contractions, while RLX showed any effect on myometrial contractions. Studied PCBs increased also (P<0.05) secretion of P4 and OT from luteal cells. It is suggested that PCBs can decreased the sensitivity of myometrium on RLX but their direct effect on RLX function have to be further investigated.

Oxytocin in cesarean-sections. What's new?

Oxytocin is the uterotonic agent of choice in the prevention and treatment of postpartum uterine atony. Nevertheless, there is no consensus on the optimal dose and rate for use in cesarean sections. The use of high bolus doses (e.g., 10 IU of oxytocin) can determine deleterious cardiovascular changes for the patient, especially in situations of hypovolemia or low cardiac reserve. Furthermore, high doses of oxytocin for prolonged periods may lead to desensitization of oxytocin receptors in myometrium, resulting in clinical inefficiency.

Oxytocin in cesarean-sections. What's new?

Oxytocin is the uterotonic agent of choice in the prevention and treatment of postpartum uterine atony. Nevertheless, there is no consensus on the optimal dose and rate for use in cesarean sections. The use of high bolus doses (e.g., 10IU of oxytocin) can determine deleterious cardiovascular changes for the patient, especially in situations of hypovolemia or low cardiac reserve. Furthermore, high doses of oxytocin for prolonged periods may lead to desensitization of oxytocin receptors in myometrium, resulting in clinical inefficiency.

Comparative Analysis of the ERα/ERβ Ratio and Neurotensin and its High-affinity Receptor in Myometrium, Uterine Leiomyoma, Atypical Leiomyoma, and Leiomyosarcoma

Deregulated steroids are involved in different hormone-dependent tumors, including benign and malignant uterine neoplasms. Leiomyomas (LM) are estrogen and progesterone-dependent benign tumors, whereas "bizarre or atypical LMs" (AL) are considered a subgroup of LM and clinically benign, although their malignant potential is suspect. Uterine leiomyosarcomas (LMS) are malignant smooth muscle tumors, and ovarian steroids may control their growth. Estrogen effects are mediated by 2 receptors, estrogen receptors (ER) α and β, and the ratio of both receptors seems to be a critical parameter in the estrogen-mediated carcinogenic process. Estradiol induces the expression of neurotensin (NTS), and the coupling of this peptide with its high-affinity receptor, NTS1, has been involved in the regulation of tumoral cell growth. Given the importance of these markers in tumor development, we aim to determine the status of ERα and ERβ in the myometrium and LM, AL, and LMS, concomitantly with the expression of NTS/NTS receptor 1 in these tumors. For that purpose, we use immunohistochemistry for all markers analyzed and in-situ hybridization to detect NTS mRNA. These data suggest that LMS are estrogen-dependent tumors, which may use NTS as an autocrine growth factor. In addition, the phenotype of AL with regard to ERα and ERβ status and NTS expression is closer to LMS than LM; thus, a potential malignization of this tumor is feasible.

Reduced expression of CRH receptor type 1 in upper segment human myometrium during labour

BackgroundCorticotropin-releasing hormone (CRH) and CRH-related peptide are shown to modulate uterine contractility through two CRH receptor subtype, CRH-R1 and CRH-R2 during pregnancy. Through different signaling pathways, CRH-R1 maintains myometrial quiescence whereas CRH-R2 promotes smooth muscle contractility. We hypothesized that the expression of CRH receptors in myometrium might be changed during pregnancy and labour.MethodImmunohistochemistry, Western blot and RT-PCR were used to quantify the cellular localization, the protein levels and the mRNA variants of both CRH-R1 and CRH-R2 in upper segment (US) and lower segment (LS) myometrium from nonpregnant and pregnant women at term before or after labour.ResultsCRH-R1 and CRH-R2 were predominately localized to myometrial smooth muscle cells in US and LS. The protein level of CRH-R1 in US was significantly down-regulated in pregnancy, with a further decrease at the onset of labour. However, the expression of CRH-R1 in LS remained unchanged during pregnancy and labour. No significant changes in CRH-R2 expression were observed in US or LS. Six variants of CRH-R1, CRH-R1alpha,-R1beta,-R1c, -R1e,-R1f and -R1g, were identified in nonpregnant and pregnant myometrium. CRH-R2alpha was identified in pregnant myometrium, whereas CRH-R2beta was identified in nonpregnant myometriumConclusionCRH-R1 and CRH-R2 are expressed in nonpregnant and pregnant US and LS myometrium. Changed expression of CRH receptors during labour may underlie the initiation of uterine contractility during parturition.

Uterine Stretch Regulates Temporal and Spatial Expression of Fibronectin Protein and Its Alpha 5 Integrin Receptor in Myometrium of Unilaterally Pregnant Rats1

The adaptive growth of the uterus during pregnancy is a critical event that involves increased synthesis of extracellular matrix (ECM) proteins and dynamic remodeling of smooth muscle cell (SMC)-ECM interactions. We have previously found a dramatic increase in the expression of the mRNAs that encode fibronectin (FN) and its alpha5-integrin receptor (ITGA5) in pregnant rat myometrium near to term. Since the myometrium at term is exposed to considerable mechanical stretching of the uterine wall by the growing fetus(es), the objective of the present study was to examine its role in the regulation of FN and ITGA5 expression at late gestation and during labor. Using myometrial tissues from unilaterally pregnant rats, we investigated the temporal changes in Itga5 gene expression in gravid and empty uterine horns by Northern blotting and real-time PCR, in combination with immunoblotting and immunofluorescence analyses of the temporal/spatial distributions of the FN and ITGA5 proteins. In addition, we studied the effects of early progesterone (P4) withdrawal on Itga5 mRNA levels and ITGA5 protein detection. At all time-points examined, the Itga5 mRNA levels were increased in the gravid uterine horn, compared to the empty horn (P < 0.05). Immunoblot analysis confirmed higher ITGA5 and FN protein levels in the myometrium, associated with gravidity (P < 0.05). Immunodetection of ITGA5 was consistently high in the longitudinal muscle layer, increased with gestational age in the circular muscle layer of the gravid horn, and remained low in the empty horn. ITGA5 and FN immunostaining in the gravid horn exhibited a continuous layer of variable thickness associated directly with the surfaces of individual SMCs. In contrast to the effects of stretch, P4 does not appear to regulate ITGA5 expression. We speculate that the reinforcement of the FN-ITGA5 interaction: 1) contributes to myometrial hypertrophy and remodeling during late pregnancy; and 2) facilitates force transduction during the contractions of labor by anchoring hypertrophied SMCs to the uterine ECM.

Magnesium sulphate suppresses ATP receptors in myometrial cells to inhibit uterine contractility for tocolysis

TO INHIBIT UTERINE CONTRACTILITY FOR TOCOLYSIS HIROSHI MIYOSHI, SATOSHI URABE, RIKAKO SHIMAZUTSU, OSAMU SAMURA, HISAYA FUJIWARA, YOSHIKI KUDO, Hiroshima University, OB/GYN, Hiroshima, Japan OBJECTIVE: Magnesium sulphate is commonly used in clinical treatment for tocolysis. Magnesium ions (Mg) suppress the strength and frequency of contractions but the mechanism is less understood. We have reported that non-selective cation channels (NSCCs) were suggested to regulate pacemaker potentials to generate rhythmical contractions. One candidate for myometrial NSCC is a ATP receptor. The purpose of this study is to examine the effect of Mg on ATP receptor currents and identify myometrial ATP receptors. STUDY DESIGN: ATP receptor currents and membrane potentials were recorded from rat myometrial cells isolated at days 18-22 of pregnancy using the patch clamp method and microelectrodes. The expression of ATP receptors was measured in pregnant rat myometrium by real time PCR (ABI 7700) with TaqMan probes (ABI). RESULTS: Extracellular ATP induced NSCC currents in these preparations. These currents were induced by ADP, GTP, UTP, 2-methylthio ATP and abmethylene ATP and were blocked by suramin and PPADS (blockers of P2X receptor). ATP depolarized cell membrane from a resting potential of 50 mV to 20 mV, indicating these currents may regulate uterine contractility. External application of Mg inhibited these currents, and also suppressed the ATP induced depolarization. The expression of mRNA was checked for P2X receptors. P2X1, 4 and 7 were measurable and the expression of P2X4 in the late pregnancy was increase by four times compared with non-pregnant myometrium. The properties of ATP receptor currents were similar to those of P2X4 or P2X7 currents. These findings indicate P2X4 or P2X7 are the main functional component of ATP receptor in myometrium. CONCLUSION: ATP receptor currents are observed in myometrial cells and are suggested to regulate the frequency of contractions. Blockade of ATP receptors by Mg may be one of the mechanisms for inhibiting uterine contraction in tocolysis.

Identification and localization of prostaglandin E2 receptors in upper and lower segment human myometrium during pregnancy

Prostaglandin E2 (PGE2) plays a key role in the maintenance of human pregnancy and labour onset. PGE2 can elicit diverse actions within the uterus depending on the PGE2 receptors (EP1, EP2, EP3 and EP4) expressed. By signalling through different intracellular pathways the EP receptors may inhibit or promote smooth muscle contractility. Nine different EP3 receptor splice variants have been identified with divergent signalling pathways. RT-PCR and immunohistochemistry were utilized to identify and localize EP receptor isoforms within the upper segment (US) and lower segment (LS) myometrium. EP1 was significantly increased in the LS myometrium with term labour. EP3 (and EP3 splice variants EP3I(1b), EP3II, EP3III and EP3IV) was down-regulated in pregnancy (US and/or LS) with a further decrease at term labour in the LS. Overall, expression of EP2 was significantly higher in the LS while EP3 was significantly higher in the US. No significant EP4 changes were observed. Consistent with the RT-PCR results, immunohistochemistry confirmed the presence and, interestingly, showed nuclear localization of EP receptors in the myometrium with higher EP1 expression and lower expression of EP3. The differential regulation of EP receptors within the myometrium indicates that they may play a role in controlling the onset and maintenance of human labour.

Expression, localization and function of prostaglandin receptors in myometrium

Prostaglandins (PGs) play a role in the initiation and maintenance of labor, acting via specific relaxatory or contractile receptors on myometrium. Myometrial response to addition of PGs may be determined by the type and concentration of receptor expressed. Autoradiographic and ligand binding studies suggest a topographic distribution of receptors between fundus, lower segment, and cervix, and that hormonally regulated changes in expression occur with advancing gestation and labor. These receptors have now been cloned and sequenced allowing molecular studies. Current dogma suggests functional regionalization of the pregnant human uterus occurs with the lower segment displaying a contractile phenotype throughout gestation changing to a relaxatory phenotype at labor to allow passage of the fetal head whereas the upper segment has a relaxatory phenotype throughout most of gestation to accommodate the growing fetus and adopts a contractile phenotype for expulsion at labor. Studies to determine the role of PG receptors in this phenomenon are currently underway.

Expression of prostanoid receptors by myometrium and cervix in response to cyclooxygenase (COX-2) inhibition in the rabbit model of RU486-induced preterm delivery

Fetal membranes express elevated levels of COX-2 at the onset of labor. Selective COX-2 inhibitors are being considered for the management of preterm labor. Prostanoid receptors are linked to various second messengers and mediate vessel constriction or dilation. EP3 prostanoid receptor plays an important regulatory role in myometrial contractility. We evaluated the expression of prostaniod receptors in myometrium and cervix in response to COX-2 inhibition in a rabbit model of RU486-induced preterm delivery.

ETHNIC VARIATIONS IN UTERINE LEIOMYOMA BIOLOGY ARE NOT CAUSED BY DIFFERENCES IN MYOMETRIAL ESTROGEN RECEPTOR ALPHA LEVELS

Uterine leiomyomas develop in women of reproductive age and regress after menopause, suggesting that they grow in a steroid hormone-dependent fashion. Furthermore, it is widely accepted that symptomatic uterine leiomyomas occur at a twofold to threefold higher frequency in black women than in white women. The present study was designed to investigate a possible physiologic role of racial differences in the myometrial estrogen receptor alpha in this phenomenon. We compared the expression of the estrogen receptor and progesterone receptor in myometrium by ligand-binding assay and the estrogen receptor alpha by real-time polymerase chain reaction in women from different ethnic backgrounds who have uterine leimyoma. Estrogen receptor and progesterone receptor concentrations and estrogen receptor alpha transcription levels were not statistically different between ethnic backgrounds. Neither on a transcriptional nor on a protein level were there statistically relevant differences in steroid hormone receptor levels. A causative role for these receptors in the ethnic variation of leiomyoma biology seems unlikely.

Ethnic variations in uterine leiomyoma biology are not caused by differences in myometrial estrogen receptor alpha levels.

Uterine leiomyomas develop in women of reproductive age and regress after menopause, suggesting that they grow in a steroid hormone-dependent fashion. Furthermore, it is widely accepted that symptomatic uterine leiomyomas occur at a twofold to threefold higher frequency in black women than in white women. The present study was designed to investigate a possible physiologic role of racial differences in the myometrial estrogen receptor alpha in this phenomenon. We compared the expression of the estrogen receptor and progesterone receptor in myometrium by ligand-binding assay and the estrogen receptor alpha by real-time polymerase chain reaction in women from different ethnic backgrounds who have uterine leiomyoma. Estrogen receptor and progesterone receptor concentrations and estrogen receptor alpha transcription levels were not statistically different between ethnic backgrounds. Neither on a transcriptional nor on a protein level were there statistically relevant differences in steroid hormone receptor levels. A causative role for these receptors in the ethnic variation of leiomyoma biology seems unlikely.

Expression of Gsalpha, connexin-43, connexin-26, and EP1, 3, and 4 receptors in myometrium of prelabor singleton versus multiple gestations and the effects of mechanical stretch and steroids on Gsalpha.

We tested the hypothesis that multiple pregnancies would be associated with altered expression of the following three groups of proteins that are key regulators of myometrial function: (i) Gsalpha, (ii) connexins-43 and 26, and (iii) prostanoid EP1, EP3, and EP4 receptors. An in vitro model was used to determine the effects of mechanical stretch on myometrial cell Gsalpha expression. Then the effects of the steroid hormones beta-estradiol and progesterone were tested on Gsalpha expression in vitro. All in vitro studies were performed using myometrium from nonlaboring women. There were no differences in the expression of Gsalpha, prostaglandin E2 receptors, or gap junction proteins in myometrium of singleton versus multiple pregnancies. Mechanical stretch did not alter Gsalpha expression in vitro, and Gsalpha expression was unaffected by steroid hormones. These results suggest that the methods whereby stretch can promote myometrial contraction are complex or require additional factors than those tested here. Alternatively, cases of multiple gestation that do not result in preterm labor perhaps compensate for the increased stretch by preventing aberrant expression of the proteins investigated in this study.

Expression of Gsα, Connexin-43, Connexin-26, and EP1, 3, and 4 Receptors in Myometrium of Prelabor Singleton Versus Multiple Gestations and the Effects of Mechanical Stretch and Steroids on Gsα

Expression of Gsα, Connexin-43, Connexin-26, and EP1, 3, and 4 Receptors in Myometrium of Prelabor Singleton Versus Multiple Gestations and the Effects of Mechanical Stretch and Steroids on Gsα

Interleukin 8 production and interleukin 8 receptor expression in human myometrium and leiomyoma

Objective: Interleukin 8 is a potent chemoattractant cytokine that is expressed in a variety of human tumors and is known to induce mitogenesis. We aimed to investigate the production of interleukin 8 and the expression of its receptor in myometrium and leiomyoma, in which we hypothesized that interleukin 8 may contribute to cellular proliferation. Study Design: Myometrial and leiomyoma tissue pairs (n = 14) were obtained from human uteri after hysterectomy conducted for leiomyomatous uterus. Expression of interleukin 8 and interleukin 8 receptor type A was identified in the leiomyomatous myometrium by means of specific antibodies directed against interleukin 8 and interleukin 8 receptor type A for immunohistochemical detection. Interleukin 8 production by cultured cells was measured by enzyme-linked immunosorbent assay. The regulation of interleukin 8 messenger ribonucleic acid expression was assessed by means of the Northern blot analysis after treatment of myometrial cells with interleukin 1α and tumor necrosis factor α. Myometrial cell proliferation was determined by means of colorimetric assay after cells were treated with interleukin 8 and antihuman interleukin 8 neutralizing antibody. Results: Immunostaining for both interleukin 8 and interleukin 8 receptor type A was stronger in the myometrium adjacent to leiomyoma compared with leiomyoma itself (2-fold, P <.05). Compared with samples from nonusers, samples from patients who had used gonadotropin-releasing hormone agonists revealed a trend for decreased staining for both interleukin 8 and interleukin 8 receptor type A. Interleukin 1α and tumor necrosis factor α caused a time- and dose-dependent increase in interleukin 8 production by myometrial cells (P <.001). There was a dose-dependent inhibition of cell proliferation with antihuman interleukin 8 antibody to 55% of the control (P <.001). Conclusion: Our demonstration of high levels of interleukin 8 and its receptor in myometrium immediately surrounding leiomyoma and the inhibition of cell proliferation when interleukin 8 is blocked by a neutralizing antibody suggest a potential role for interleukin 8 in the growth of myometrial tissue surrounding leiomyomatous tissue. This study could lead to a better understanding of potential involvement of cytokines in leiomyoma growth and in gonadatropin-releasing hormone agonist–induced regression. (Am J Obstet Gynecol 2001;184:559-66.)

Altered gene expression of endothelin-A and endothelin-B receptors, but not endothelin-1, in myometrium and placenta from pregnancies complicated by preeclampsia.

The aim of the present study was to compare the mRNA expression of endothelin-1 (ET-1), ET-1 receptors ET(A) and ET(B) in myometrium and placenta obtained from biopsies collected from women with preeclampsia (n=10) or normal pregnant (n=12). The mRNA levels of ET-1 ET(A) and ET(B) were determined using RT-PCR and expressed as arbitrary units after correction for control GAPDH gene mRNA levels. The mRNA levels of ET-1 in myometrium and placenta were not altered in women with preeclampsia compared to normal pregnant. The mRNA expression of ET(A) was significantly reduced (p<0.05) in both placenta and myometrium from women with preeclampsia. The mRNA levels of ET(B) were similar in placentas from both preeclamptic and normal pregnant women, but higher in myometrium (p<0.05) from women with preeclampsia. These results indicate that the higher levels of ET-1 seen in preeclamptic women do not depend on an altered mRNA transcription of ET-1. The significantly reduced mRNA expression of ET(A) receptor in myometrium and placenta in women with preeclampsia might represent downregulation of the receptors due to the increased levels of ET-1 in uteroplacental circulation in this disorder. Much more research is needed before the role of ET(B) receptors in preeclampsia can be clarified.