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Kunihiro Okamura

Publications and source records attributed to Kunihiro Okamura.

At least 37 records · Page 2Linked to original sources
PubMed2005

Expression of estrogen-responsive finger protein (Efp) is associated with advanced disease in human epithelial ovarian cancer.

OBJECTIVE: The estrogen-responsive ring finger protein (Efp) gene, one of estrogen receptor (ER) target genes, is considered to be essential for estrogen-dependent cell proliferation. To understand the estrogenic action on ovarian cancer, we studied the relationships between Efp and ERs expressions and the correlations of Efp expression with clinicopathological parameters in epithelial ovarian cancer. METHODS: The protein expressions for Efp, ERalpha and ERbeta were examined by immunoblotting in 12 ovarian cancer cell lines. Efp mRNA expressions were evaluated by quantitative RT-PCR in 12 ovarian cancer cell lines. A total of 100 surgical specimens diagnosed as epithelial ovarian cancer were examined immunohistochemically using antibodies for Efp, ERalpha and ERbeta. RESULTS: Efp protein was detected in 8 out of 12 cell lines. In Efp protein-positive cell lines, Efp mRNA was expressed higher than that in negative (P=0.021). All of the Efp protein-positive cell lines simultaneously expressed either ERalpha or ERbeta protein. By immunohistochemical staining, Efp immunoreactivity was detected in 63 out of 100 ovarian cancer specimens and positive signals were in the cytoplasm of carcinoma cells. There were significant correlations between Efp and ERalpha, ERbeta immunoreactivity (Efp and ERalpha, P=0.022; Efp and ERbeta, P=0.032). Efp expression was significantly higher in a subgroup with serous adenocarcinoma (P=0.010) and with advanced disease (P=0.026). No significant relationship was detected between Efp immunoreactivity and overall survival. CONCLUSION: The expression of Efp was detected in human epithelial ovarian cancer and high expression of Efp was correlated with advanced disease and serous adenocarcinoma, and ERs status.

Adenocarcinoma↗
PubMed2005

Dynamics of microtubules and positioning of female pronucleus during bovine parthenogenesis.

The zygote centrosome, consisting of both paternal and maternal centrosomal components, is the microtubule-organizing center necessary for pronuclear migration and positioning in fertilization. Maternal centrosomal function in microtubule organization and pronuclear positioning, however, remains unclear. In the present study, we sought to elucidate the function of maternal centrosomes during bovine parthenotes in the microtubule organizational processes required to move the pronucleus to the cell center without sperm centrosomal components. Microtubule organization, pronuclear position, and distribution of gamma-tubulin, which is thought to be the major component of maternal centrosomal material, were imaged by immunocytochemistry and conventional epifluorescence microscopy. In bovine parthenotes treated with paclitaxel, a microtubule-stabilizing drug, the cytoplasmic microtubule asters became organized after chemical activation, and the microtubules radiated dynamically toward the female pronucleus. The microtubule patterns correlated well with pronuclear movement to the cell center. Microtubules aggregated at regions of gamma-tubulin concentration, but gamma-tubulin did not localize to a spot until the first interphase of bovine parthenogenesis. These findings indicate that gamma-tubulin is responsible for microtubule organization as the maternal centrosome. In bovine parthenogenesis, the maternal centrosome then organizes cytoplasmic microtubules to move the female pronucleus into the cell center. We propose that the maternal centrosome plays a role as a functional centrosome despite the lack of a sperm contribution, making this structure less competent for microtubule organization in comparison with centrosomes containing sperm centrosomal components.

Animals↗
PubMed2005

Decrease and senescence of endothelial progenitor cells in patients with preeclampsia.

BACKGROUND: In preeclampsia, the precise mechanism of impaired vascular function is still unclear. We hypothesized that cellular function of circulating endothelial progenitor cells (EPCs) might be impaired in patients with preeclampsia. OBJECTIVE: The objective of this study was to investigate the number and status of cellular senescence of EPCs in the circulation of women with preeclampsia. METHODS: Circulating EPCs were cultured from patients with preeclampsia (n = 8) and normotensive pregnant women (n = 7). EPC numbers were assessed by colony-forming unit (CFU) methodology as previously reported. In addition, to assess cellular senescence, we measured endogenous beta-galactosidase activity. Moreover, we assessed whether the serum level of C-reactive protein (CRP), a marker for systemic inflammation, was associated with cellular impairment of EPCs. RESULTS: The number of circulating EPCs was decreased in women with preeclampsia controls (median, 10.0 vs. 34.0 CFU; P < 0.01). The rate of cellular senescence was significantly increased in patients with preeclampsia (33.9%) compared with that in controls (22.9%; P < 0.05). Patients with preeclampsia were divided into two subgroups: the CRP-negative group (CRP, <0.1 mg/dl; n = 4) and the CRP-positive group (CRP, > or =0.1 mg/dl; n = 4). Interestingly, EPC CFU counts were markedly decreased in CRP-positive patients compared with those in CRP-negative patients (5.0 and 25.0 CFU, respectively; P < 0.05). Median values for cellular senescence were greater in the CRP-positive group than in the CRP-negative group, although this did not achieve statistical significance (43.5% and 33.3%, respectively; P = 0.12). CONCLUSION: Depletion and cellular aging of EPCs in patients with preeclampsia might be associated with endothelial dysfunction and could be affected by systemic inflammation.

Adult↗
PubMed2005

A trial to restore defective human sperm centrosomal function.

BACKGROUND: In human fertilization, sperm centrosome function is essential for male and female pronuclear movement and fusion. In this study, we investigated the possibility of restoring human sperm centrosomal function in sperm exhibiting abnormalities in microtubule organization. METHODS: Semen was obtained from both a fertile donor and a patient with dysplasia of the fibrous sheath (DFS). Following heterologous ICSI using human sperm, we examined microtubules and chromatin configuration in bovine oocytes. Sperm were treated with dithiothreitol (DTT) prior to ICSI, while the oocytes were treated with the cytoskeletal stabilizer paclitaxel after ICSI. RESULTS: The combination of DTT and paclitaxel treatment induced microtubule organization in dead sperm from the fertile donor following heterologous ICSI. This treatment, however, was not effective for DFS sperm. In addition, expression of centrin, a protein functioning within the sperm centrosome, was reduced in DFS sperm from that of the normal levels observed in fertile donor sperm. CONCLUSION: These results indicate that sperm centrosomal function could be induced by the treatment of sperm with DTT before ICSI and of oocytes with paclitaxel after ICSI. DFS sperm are likely to exhibit such severe dysfunction of sperm centrosome that cannot be compensated for by this treatment; therefore, this method may be a practical way to discern the degree of sperm centrosomal dysfunction.

Adult↗
PubMed2005

Reproduction of menstrual changes in transplanted human endometrial tissue in immunodeficient mice.

BACKGROUND: Cultures of human endometrial tissue are useful for analysing the mechanisms underlying the menstrual cycle. However, long-term culture of endometrial tissue is difficult in vitro. Xenotransplantation of normal human endometrial tissue into immunodeficient mice could allow prolonged survival of the transplanted tissues. METHODS: Proliferative-phase endometrial tissue samples from three women were transplanted into the subcutaneous space of ovariectomized, immunodeficient, non-obese diabetic (NOD)/severe combined immunodeficiency (SCID)/gammaC(null) (NOG) mice. The mice were treated with 17beta-estradiol (E2) for the first 14 days after transplantation, followed by E2 plus progesterone for the next 14 days. The transplants were investigated morphologically and immunohistochemically at various times after implantation. RESULTS: The transplanted tissues contained large numbers of small glands, pseudostratification of the nuclei and dense stroma after treatment with E2 alone. After treatment with E2 plus progesterone, subnuclear vacuolation, luminal secretion and decidualization of the stroma were observed. When the hormone treatment ceased, tissue destruction occurred and the transplants returned to the proliferative phase. Lymphocytes were identified immunohistochemically: the numbers of CD56-positive and CD16-negative cells increased significantly in the stroma during the late secretory phase (day 28). CONCLUSIONS: Human endometrial tissue transplanted into NOG mice showed similar histological changes to eutopic endometrial tissue during treatment with sex steroid hormones for 1 month. Moreover, lymphocytes were produced in the transplanted human endometrial tissue. This system represents a new experimental model of the human endometrium in vivo.

Adult↗
PubMed2005

Dynamic changes in the cytoskeleton during human spermiogenesis.

OBJECTIVE: To investigate the structural changes in the cytoskeleton (microtubules, microfilaments) and examine the expression of centrosomal functional proteins during human spermiogenesis. DESIGN: Immunofluorescent staining of human spermiogenic cells. SETTING: University hospital and IVF clinic. PATIENT(S): Human testicular tissues were obtained by testicular sperm aspiration (TESA) under informed consent. Three cases of obstructive azoospermia, with confirmed normal spermatogenesis, were examined. INTERVENTION(S): Spermatogenic cells were fixed with microtubule-stabilizing buffer. Immunocytochemical detection of microtubules, microfilaments, and centrosome was performed using monoclonal antibodies against alpha- and beta-tubulin, phalloidin, and functional centrosomal proteins. MAIN OUTCOME MEASURE(S): Samples were examined using epifluorescence and laser scanning confocal microscopes. RESULT(S): During the Sb2 period, microtubules formed the manchette structure, which extended from the equator of the nucleus through the cytoplasm. Microfilaments were organized in the periacrosamal region during spermiogenesis (Sa to Sd). Although centrin was observed throughout the spermiogenic period, gamma-tubulin was detected only in the Sb2 period. CONCLUSION(S): Dynamic cytoskeletal movement was observed during human spermiogenesis. Cytoskeletal rearrangements in the Sb2 period appear to play important roles in the morphologic changes that occur during human spermiogenesis. Studies of the cytoskeletal system during spermiogenesis may help identify some causes of male infertility (e.g., teratozoospermia, maturation arrest).

Adult↗
PubMed2005

Orphan nuclear receptor DAX-1 in human endometrium and its disorders.

DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1) is a recently characterized member of the orphan nuclear receptor family. DAX-1 functions as a global negative regulator of steroid hormone production. It inhibits adrenal 4 binding protein (Ad4BP)/steroidogenic factor-1 (SF-1) pathway-dependent P450arom expression in cultured human endometriotic stromal cells and acts as a corepressor for estrogen receptors (ER). In this study we first examined the localization of DAX-1 in 46 normal cycling endometria, 36 cases of endometrial hyperplasia and 103 cases of endometrial carcinoma by using immunohistochemistry to elucidate the possible involvement of DAX-1 and its correlation to the status of Ad4BP/SF-1, a universal transcription factor of steroidogenesis. We then evaluated DAX-1 mRNA expression, using quantitative reverse transcription-polymerase chain reaction for DAX-1 in 33 cases of endometrial carcinoma for further characterization. We subsequently correlated these findings with various clinicopathological parameters of the cases. Ad4BP/SF-1 immunoreactivity was not detected in any human endometria examined. A significant inverse correlation was detected between the status of DAX-1 immunoreactivity and histological grade (P = 0.0003) in endometrial carcinoma. The labeling index (LI) values of DAX-1 in normal endometrium during the secretory phase (P < 0.0001) and hyperplasia (P < 0.0001) were significantly higher than that of carcinoma. No significant correlations were detected between DAX-1 immunoreactivity and amounts of aromatase mRNA. There was a statistically significant positive correlation between DAX-1 and ERalpha (P = 0.006) and ERbeta LI (P < 0.001). These findings suggest that DAX-1 may inhibit the proliferation and progression of endometrial carcinoma through inhibition of estrogenic actions, possibly by interacting with ER present in carcinoma cells, rather than regulating in situ steroidogenesis.

Adrenal Glands↗
PubMed2005

Safe techniques in surgery for hysteroscopic myomectomy.

Hysteroscopic myomectomy is regarded as the best treatment for patients with submucous myomata. However, this procedure has a number of associated complications, including uterine perforation, cervical laceration, hyponatremia and hemorrhage, especially in cases of sessile submucous myomata. To avoid these problems, it is important to make well-advised preparations and manipulations both pre- and intraoperatively. The main surgical considerations for safe hysteroscopic myomectomy are shortening the operating time and avoiding cutting too deeply into the myometrium. With these requirements in mind, a combination of techniques using vaporization and a powerful oxytocic agent, such as prostaglandin F-2alpha, appears to be the safest method of carrying out hysteroresectoscopy for unpedunculated sessile submucous myomata.

Female↗
PubMed2005

Successful conservative treatment of a cesarean scar pregnancy with uterine artery embolization.

Ectopic pregnancy developing in a previous Cesarean section scar is rare and is associated with catastrophic complications, such as uterine rupture and uncontrollable bleeding, which may lead to loss of the uterus. The operative treatments that have been reported for cesarean scar pregnancy are dilatation and curettage and excision of trophoblastic tissues using either laparotomy or laparoscopy. Recently, conservative treatment of scar pregnancy with locally and/or systemically administered methotrexate (MTX) has been reported. However, recent reports demonstrated that cases treated with MTX sometimes required laparotomy later because of excessive bleeding. In this series of cases we have demonstrated that viable cesarean scar pregnancies can be treated safely by selective transarterial embolization in combination with subsequent dilatation and curettage and local or systemic injections of MTX. In these three cases, uterine artery embolization proved to be a useful procedure for preventing uncontrollable bleeding and unnecessary uterine loss.

Abortion, Induced↗
PubMed2005

Ber-EP4 and anti-calretinin antibodies: a useful combination for differential diagnosis of various histological types of ovarian cancer cells and mesothelial cells.

The differential diagnosis between reactive mesothelial cells and ovarian carcinoma cells is often difficult in cytologic specimens. Immunocytochemical procedures have been utilized in assisting this differential diagnosis, with limitations. Furthermore, previous studies examined only serous type but not other histological types of ovarian carcinoma cases. Therefore, we evaluated the practical value of various epithelial and mesothelial markers in differential diagnosis of these two types of cells. Various types of ovarian carcinoma (serous, n = 22; mucinous, n = 10; endometrioid, n = 7; clear cell, n = 10) and benign mesothelial tissues (n = 15) were studied by immunohistochemistry. We then studied effective panels of antibodies by immunohistochemistry in 43 cytologic specimens of ascites or peritoneal lavage fluid consisting of 20 reactive mesothelium and 23 adenocarcinomas of the ovary. In the tissue specimens, Ber-EP4, a monoclonal antibody of epithelial antigen, and a polyclonal antibody against calretinin, which is expressed in mesothelium, are used in differentiating reactive mesothelial cells from ovarian carcinoma. In cytologic specimens, the sensitivity and specificity of Ber-EP4 were 100% and 90%, respectively. The sensitivity and specificity of the anti-calretinin antibody were 90% and 91%, respectively. Using multiple regression analysis, the correlation coefficient between epithelial antigen and calretinin reactivity was r = 0.938, with a significance level of p < 0.0001. In conclusion, the combined immunostaining of cytologic specimens for Ber-EP4 and the anti-calretinin antibody is helpful for the differential diagnosis between mesothelial cells and not only serous type, but also mucinous, endometrioid and clear cell types of ovarian cancer cells.

Antibodies↗
PubMed2004

Circulating endothelial progenitor cells during human pregnancy.

The precise molecular and cellular mechanisms that regulate maternal vascular development during gestation are largely unknown. Endothelial progenitor cells (EPCs), which play an important role in vascular homeostasis, have been discovered in the circulation. We examined the level of circulating EPCs throughout uncomplicated pregnancies (n = 20) and assessed the correlation between serum estradiol levels and the number of EPCs. The number of circulating EPCs increased gradually and paralleled the progression of gestational age. In addition, the number of EPCs correlated significantly with the level of serum estradiol. The present study suggests that EPCs may play an important role in the regulation and maintenance of the placental development and vascular integrity during pregnancy.

Adaptation, Physiological↗
PubMed2004

Genetic significance of skewed X-chromosome inactivation in premature ovarian failure.

To determine the relationship between premature ovarian failure (POF) and skewed X-chromosome inactivation (XCI), karyotype, and XCI status in 43 patients with POF (group I) and 43 age-matched control women with regular menstrual cycles (group II) were evaluated. Evaluation of XCI status was based on the CAG triplet repeat polymorphism assay in the androgen receptor gene after sodium bisulfite treatment of DNA samples, and XCI patterns were classified as random (XCI < 70% skewing) or skewed (> or =70%). Furthermore, skewed XCI was classified under three different thresholds (> or =70, > or =80, or > or =90%). Karyotyping by G-banding and fluorescence in situ hybridization (FISH) on peripheral blood lymphocytes showed that one patient in group I had a deletion of Xq22, and another was 47,XXX. The frequency of low-level 45,X/46,XX mosaicism was nearly equal in both groups. In women without any X-chromosomal aberrations, the incidence of skewed XCI in group I was significantly higher than in group II on all threshold levels. Furthermore, extremely skewed XCI (> or =90%) was observed only in group I. These results indicate that POF may be caused by some underlying genetic disorders, which may induce skewed XCI.

Adult↗
PubMed2004

Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma.

PURPOSE: Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined. EXPERIMENTAL DESIGN: We first examined the expression of steroid sulfatase and estrogen sulfotransferase in 6 normal endometrium and 76 endometrial carcinoma using immunohistochemistry to elucidate the possible involvement of steroid sulfatase and estrogen sulfotransferase. We then evaluated the enzymatic activity and the semiquantitative analysis of mRNA using reverse transcription-PCR in 21 endometrial carcinomas. We correlated these findings with various clinicopathological parameters including the expression of aromatase, 17beta-hydroxysteroid dehydrogenase type 1 and type 2. RESULTS: Steroid sulfatase and estrogen sulfotransferase immunoreactivity was detected in 65 of 76 (86%) and 22 of 76 (29%) cases, respectively. Results of immunoreactivity for steroid sulfatase and estrogen sulfotransferase were significantly correlated with those of enzymatic activity and semiquantitative analysis of mRNA. No significant correlations were detected among the expression of the enzymes involved in intratumoral estrogen metabolism. There was a significant correlation between steroid sulfatase/estrogen sulfotransferase ratio and clinical outcomes of the patients. However, there were no significant differences between steroid sulfatase or estrogen sulfotransferase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients. CONCLUSIONS: Results of our study demonstrated that increased steroid sulfatase and decreased estrogen sulfotransferase expression in human endometrial carcinomas may result in increased availability of biologically active estrogens and may be related to estrogen-dependent biological features of carcinoma.

17-Hydroxysteroid Dehydrogenases↗
PubMed2004

Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation.

PURPOSE: In this study, we examined the promoter methylation status and expression of 14-3-3 sigma and evaluated its clinical significance in epithelial ovarian cancer. EXPERIMENTAL DESIGN: Twelve ovarian cancer cell lines; 2 ovarian surface epithelial cell lines; and 8 normal, 8 benign, 12 borderline, and 102 ovarian cancer tissues were examined. Methylation-specific PCR, quantitative reverse transcription-PCR, and immunohistochemistry were used to evaluate methylation status and expression of 14-3-3 sigma gene and protein. RESULTS: Among the 12 ovarian cancer cell lines, the presence of a methylated band was detected in seven cell lines. Median values of relative 14-3-3 sigma gene expression in cancers with methylation (3.27) were significantly lower than those without methylation (16.4; P < 0.001). Treatment of 5-aza-2'-deoxycitidine resulted in the demethylation of the promoter CpG islands and reexpression. All of the normal, benign, and borderline tissues were positive for 14-3-3 sigma protein, and in ovarian cancer tissues, 73.5% (75 of 102) were positive for 14-3-3 sigma protein and was almost consistent with methylation status. Negative immunoreactivity of 14-3-3 sigma was significantly correlated with high age and serous histology, high-grade, advanced-stage residual tumor of >2 cm, high serum CA125, high Ki-67 labeling index, and positive p53 immunoreactivity. 14-3-3 sigma immunoreactivity was significantly associated with overall survival (P = 0.0058). CONCLUSIONS: Our findings suggest that 14-3-3 sigma is inactivated mainly by aberrant DNA methylation and that it may play an important role in the pathogenesis of epithelial ovarian cancer.

14-3-3 Proteins↗
PubMed2004

Centrosomal function assessment in human sperm using heterologous ICSI with rabbit eggs: a new male factor infertility assay.

Sperm centrosomal function was assessed by immunocytochemical analysis after the injection of human sperm into mature rabbit eggs. Three hours after intracytoplasmic sperm injection (ICSI), an astral microtubule array from the base of the human sperm was observed in the rabbit eggs. This sperm aster expanded in the egg cytoplasm, concomitant with pronuclear formation, and a dense microtubule array was organized at the time of pronuclear centration. Using fertile donor sperm, the sperm aster formation rate at 3 hr after ICSI was 35.0 +/- 1.5%. Using sperm from infertile patients, the average aster formation rate was lower (25.4 +/- 14.8%, P<0.05). Among infertile cases, there was no correlation between sperm aster formation rates and conventional parameters of semen analysis. However, the sperm aster formation rate correlated with the embryonic cleavage rate following human in vitro fertilization (IVF). These data suggest that this assay reflects sperm function during embryonic development after sperm entry and that reproductive success during the first cell cycle requires a functional sperm centrosome. Furthermore, sperm centrosomal function cannot be predicted from conventional parameters of semen analysis. We propose that insufficient centrosomal function could be the cause of certain cases of idiopathic infertility. These assays may lead to the discovery of new types of infertility, which have previously been treated as "unexplained infertility," and may also lead to the treatment of infertility incurable even by ICSI. Consequently, an accurate and relevant assay to help assure couples of the success of fertilization is warranted, perhaps prior to ICSI therapy.

Animals↗
PubMed2004

Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma.

BACKGROUND: Interleukin-18 (IL-18), a cytokine produced by macrophages, is capable of inducing T-lymphocyte synthesis of interferon-gamma (IFN-gamma). In this study, for the first time, the serum concentration of IL-18 and its significance as a prognostic indicator was evaluated in patients with epithelial ovarian cancer. METHODS: The serum IL-18 level was measured by an enzyme-linked immunosorbent assay (ELISA) in 69 patients with epithelial ovarian cancer and 8 healthy controls. Relationships between the IL-18 level and clinicopathological features were examined by univariate and multivariate analyses. RESULTS: The median serum IL-18 level in the ovarian cancer patients was 229.6 pg/ml, and the level was significantly elevated compared with that in the normal controls (151.3 pg/ml; P < 0.01). No significant correlations were detected between the IL-18 level and stage or histology (P = 0.08 and P = 0.12, respectively). On univariate analysis, overall survival was shown to be affected by IL-18 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-18 serum levels, while confirming the role of previously established prognostic variables, such as performance status, stage, and residual tumor. CONCLUSION: This study showed that IL-18 serum levels were elevated in ovarian cancer patients and were correlated with overall survival, although they were shown not to be an independent prognostic factor.

Adult↗
PubMed2004

Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells.

OBJECTIVE: To investigate the effects of 17beta-estradiol (E(2)) on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) synthesis in primary human uterine microvascular endothelial cells (HUMEC). DESIGN: Prospective study. SETTING: Basic research laboratory at an academic medical center. PATIENT(S): Primary HUMEC of three women donors and primary human dermal microvascular endothelial cells of three women donors (as control), purchased from a third-party source. INTERVENTION(S): The HUMEC were cultured in specific media in a humidified atmosphere with 5% CO(2) at 37 degrees C. MAIN OUTCOME MEASURE(S): Measures of COX-2 mRNA and protein, PGE(2) production, and estrogen receptor alpha and beta mRNA and protein. RESULT(S): Treatment with E(2) (10(-10) to 10(-6) M) increased COX-2 mRNA levels by 2.3-fold to 2.4-fold in HUMEC. Treatment of HUMEC with E(2) (10(-8) M) resulted in a time-dependent increase of COX-2 mRNA levels. This was accompanied by a 2.8-fold increase in COX-2 protein level and a 1.5-fold increase in PGE(2) synthesis. Pretreatment of HUMEC with a selective COX-2 inhibitor, NS-398, abolished E(2)-induced PGE(2) synthesis, suggesting that E(2) specifically up-regulates COX-2 activity. The estrogen receptor antagonist ICI 182,780 fully reversed the stimulation of COX-2 mRNA and protein levels and PGE(2) synthesis by E(2). Interestingly, estrogen receptor beta mRNA and protein were abundant in HUMEC, whereas estrogen receptor alpha mRNA or protein was barely detectable. CONCLUSION(S): We conclude that various levels of E(2) can significantly increase COX-2 expression and PGE(2) synthesis in HUMEC via the estrogen receptor.

Cells, Cultured↗