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PubMed2000

Insulin-like growth factors and insulin-like growth factor binding proteins in the endometrium. Effect of intrauterine levonorgestrel delivery.

Insulin-like growth factor (IGF) system is one of the growth factor systems that are believed to modulate steroid hormone actions in the endometrium through autocrine/paracrine mechanisms. IGF-I and IGF-II stimulate proliferation and differentiation, and maintain differentiated cell functions in several cell types in vitro. Endometrial stromal cells produce IGF-I and IGF-II as well as the high affinity IGF-binding proteins (IGFBP), whereas epithelial cells and, in a lesser amount, stromal cells contain cell membrane receptors for IGF. Oestrogen stimulates IGF-I gene expression, and IGF-II gene expression is associated with endometrial differentiation. The mRNA of six high affinity IGFBPs, which can modulate IGF actions, are expressed in human endometrium. The most abundant IGFBP in human endometrium is IGFBP-1, which is secreted by predecidualized/decidualized endometrial stromal cells in late secretory phase and during pregnancy. The primary negative regulator of IGFBP-1 production is insulin. IGFBP-1 competes with type I IGF receptor for binding of IGF in the endometrium and in cultured human trophoblastic cells. IGF-I mRNA is suppressed and mRNA encoding IGF-II and IGFBP-1 are consistently up-regulated in decidualized endometrium in women treated with the intrauterine levonorgestrel system (LNG-IUS). Strong cytoplasmic staining for IGFBP-1 was detected in decidualized endometrium in women using LNG-IUS for contraception or for endometrial protection during post-menopausal oestrogen replacement therapy. Simultaneously, oestrogen receptors were present, while progesterone receptors were hardly detectable in the endometrium by immunohistochemistry. The latter findings suggest that suppression of IGF-I action by IGFBP-1 may be one of the molecular mechanisms accounting for progestagenic and anti-oestrogenic effects of LNG-IUS in the endometrium. Consequently, examination of local IGF-I, IGF-II and IGFBP-1 expression might provide additional information when evaluating the effect of different progestins on the endometrium at the molecular level.

Contraceptive Agents, Female↗
PubMed1997

The progressive rise in the expression of alpha crystallin B chain in human endometrium is initiated during the implantation window: modulation of gene expression by steroid hormones.

Human endometrium undergoes sequential changes during the menstrual cycle and becomes receptive to implantation during a defined period in the secretory phase. We attempted to identify the genes expressed during this period by representational difference analysis (RDA). When the cDNAs of a proliferative endometrium were used as the driver and the cDNAs of a post-ovulatory day 5 endometrium were used as the tester, a number of bands were identified by RDA. DNA of the cloned RDA products revealed that the majority of the clones contained a fragment of a cDNA identical to that of a crystallin B chain. Northern blot analysis showed that the expression of the alpha crystallin B chain mRNA was absent during the proliferative phase. The expression of the mRNA of alpha crystallin B chain first appeared in the secretory phase, progressively increased during this phase and peaked in the late secretory endometria. The pattern of expression of alpha crystallin B chain mRNA in the endometrium of mature cycling baboons (Papio anubis) was similar to that seen in human endometrium. As revealed by Western blot analysis, the expression of the alpha crystallin B chain protein in human endometrium followed a pattern of expression similar to its mRNA. At the cellular level, the immunoreactive protein first appeared in the surface epithelial cells of human endometrium within the implantation window without significant immunoreactivity in the underlying glandular cells. During the mid- and late secretory phases, the intensity of staining in the epithelial cells was enhanced and an intense immunoreactivity was developed in the glandular epithelium, alpha crystallin B chain was virtually an epithelial product and no immunoreactivity for this protein was detectable in the stromal cells, endothelial cells or lymphoid cells. The expression of alpha crystallin B chain could be regulated, by medroxy progesterone acetate as well as by oestrogen withdrawal, in human endometrial carcinoma cells (EnCa-101), transplanted to nude mice. Based on the data presented here, the known function of alpha crystallin B chain and its distinct pattern of expression in human endometrium, we suggest that this protein is an important factor within the molecular repertoire that makes endometrium receptive to implantation.

Adult↗
PubMed1999

Regulation of sulphotransferase expression in the endometrium during the menstrual cycle, by oral contraceptives and during early pregnancy.

The endometrium plays a key role in reproduction, and this function is tightly regulated by endogenous and xenobiotic steroids. Sulphation, catalysed by members of the sulphotransferase (SULT) enzyme family, is a major deactivating mechanism for steroid hormones and we have investigated the expression and regulation in vivo of SULT in the human endometrium. In the normal cycling endometrium, expression of the phenol sulphotransferases SULT1A1 and SULT1A3 and the oestrogen sulphotransferase SULT1E1 were observed, with SULT1A1 and SULT1E1 expression being higher in the luteal phase than in the follicular phase. No expression of the hydroxysteroid sulphotransferase SULT2A1 was detected at any time in the endometrium. In endometrium from women taking the combined oral contraceptive pill (OCP), SULT1E1 expression was virtually absent, and SULT1A1 expression was substantially reduced. Similarly, in early pregnancy (i.e. first trimester) endometrium, SULT1E1 expression was absent, although SULT1A1 and SULT1A3 expression were unaffected. Our results with normal endometrium support in-vitro data showing that SULT1E1 expression is regulated by progesterone. However, the data obtained from OCP and early pregnancy endometrium suggest that factors other than the concentration of circulating progesterone are involved in the regulation of the expression of this important enzyme in the endometrium.

Adult↗
PubMed2002

Endometrial nuclear receptor co-factors SRC-1 and N-CoR are increased in human endometrium during menstruation.

Steroid hormone receptor co-factors are abundantly expressed in the uterus in order to modify steroid hormone receptor action, either leading to activation or repression of transcription in the endometrium. However, the role of co-factors in remodelling of the human endometrium has not been established. We therefore endeavoured to evaluate the presence of the co-activator SRC (steroid receptor co-activator)-1 and the co-repressors N-CoR (nuclear receptor co-repressor) and steroid co-repressor SMRT (silencing mediator of retinod and thyroid) receptors in the human endometrium during the different phases of the menstrual cycle. By using a real-time RT-PCR assay, we showed that SRC-1, N-CoR and SMRT mRNA are expressed in human endometrium during all phases of the menstrual cycle, as well as in inactive endometrium. Moreover, endometrial expression of SRC-1 and N-CoR mRNA increased during menstruation when compared with the other phases of the menstrual cycle (P < 0.001). Immunohistochemistry demonstrated that SRC-1 and N-CoR stain positive in the glandular epithelium and stroma in menstrual phase endometrium. The staining was weak in proliferative and secretory endometrium and absent in inactive endometrium. Our results suggest that differential expression of endometrial steroid receptor co-factors probably play a role in the regulation of human endometrium remodelling.

DNA-Binding Proteins↗
PubMed1995

Haemostatic mechanism in the endometrium: role of cyclo-oxygenase products and coagulation factors.

1. The primary mechanism of haemostasis in the endometrium of rat was studied and results were compared to that in the mesenteric artery. 2. The bleeding time of the rat endometrium as assessed by haemoglobin output was significantly decreased after pretreatment of the animals with either indomethacin (5 mg kg-1, i.v.) or meclofenamate (3 mg kg-1, i.v.) whereas the bleeding time was significantly increased in the rat mesenteric artery. 3. The bleeding time of the rat endometrium was unchanged from control values following treatment with prostacyclin (0.5 microgram kg-1 min-1, i.v.) or 1-benzylimidazole (50 mg kg-1, i.v.) whereas the bleeding times were increased in the rat mesentric artery. 4. Administration of heparin (100 units kg-1) increased the bleeding time in the rat mesenteric artery but had no effect on the bleeding time of the endometrium. 5. Superfusion of the endometrium with 16, 16-dimethyl PGE2 (1 microgram ml-1) a vasodilator, increased the bleeding time of the endometrium but superfusion of PGE2 over the mesenteric artery did not affect the bleeding time from this site. 6. Histological studies of the mesenteric artery and the endometrium following haemostatis revealed that the haemostatic plug in the mesenteric artery was mainly composed of platelets and fibrin whereas in the endometrium it was mainly composed of fibrin. 7. These findings suggest that haemostasis in the endometrium may be mediated by the vascular tone and fibrin whereas formation of the platelet plug may be primary mechanism for haemostasis in the mesenteric artery.

Animals↗
PubMedDate not supplied

Hormonal regulation of complement factor B in human endometrium.

PROBLEM: Recent investigations have demonstrated the presence of complement components in human endometrium in a cycle-specific manner. Luteal phase endometrium has been shown to synthesize complement C3 de novo, whereas proliferative endometrium produces little or no C3. Likewise factor B, which is critical to the activation of the alternative pathway of complement, has been shown to be present only in the glandular epithelium of luteal phase endometrium. This investigation was designed to determine if factor B is present in the endometrium in a high progesterone state such as pregnancy or with exogenous progesterone treatment. METHOD: Endometrial biopsies were obtained from patients on progesterone therapy. The endometrium of early pregnancy was evaluated by obtaining biopsies from patients with ectopic pregnancies as well as from patients undergoing therapeutic termination. Immunohistochemistry was performed on each biopsy using monoclonal antibodies to factor B. RESULTS: Our results demonstrate the presence of factor B in the glandular epithelial cells of the endometrium of patients treated with exogenous progesterone therapy. Additionally, factor B was localized to the glandular compartment of the endometrium from patients with ectopic gestations. Interestingly, the evaluation of an implantation site from an early gestation demonstrated factor B in the maternal decidua only; trophoblast did not exhibit the presence of factor B. CONCLUSION: Factor B exists in the endometrium in a hormone-dependent manner and is not expressed in fetal tissue in early gestation.

Complement Factor B↗
PubMed1997

Localization of T cells, interferon-gamma and HLA-DR in eutopic and ectopic human endometrium.

OBJECTIVES: Immunologic mechanisms are implicated in the pathogenesis of endometriosis and endometriosis-associated reproductive failure. The purpose of this study was to describe key immune response elements in eutopic and ectopic endometrium and to test the hypothesis that expression of CD3-positive T cells, the T-helper 1-type cytokine, IFN-gamma, and the antigen presentation marker, HLA-DR, vary throughout the menstrual cycle in eutopic endometrium and are more abundantly expressed in ectopic than in eutopic endometrium. METHODS: Eutopic and ectopic endometrium obtained at hysterectomy from 7 women with endometriosis were compared with hysterectomy specimens from 7 women with adenomyosis and 10 women without endometriosis or endometrial pathology. Tissues were formalin-fixed, paraffin-embedded, sectioned and stained using the biotin-streptavidin-alkaline phosphatase technique and antibodies to human CD3, IFN-gamma, and HLA-DR. Eutopic endometrial samples were histologically divided into menses (n = 5), proliferative (n = 9), and secretory (n = 10) phases. Positive control tissues (spleen) and negative controls (no primary antibody) were used in each experiment. RESULTS: T cells, IFN-gamma and HLA-DR-positive cells were observed in eutopic endometrial samples throughout the menstrual cycle. Glandular epithelium was CD3-negative except for CD3-positive cells surrounding and occasionally interdigitating between glandular epithelium. Glandular epithelium was IFN-gamma-positive and HLA-DR-positive in all phases except the proliferative phase. Staining was more often observed in the basalis than in the functionalis layer, ranging from patchy staining to the entire gland. T cells, IFN-gamma, and HLA-DR-positive stromal cells were more abundant in secretory endometrium than in proliferative samples. CD3, IFN-gamma, and HLA-DR-positive cells were scattered throughout the myometrium and concentrated in vessels. Higher intensity staining was observed in ectopic than in eutopic endometrium, with CD3 and HLA-DR-positive cells forming aggregates around IFN-gamma and HLA-DR-positive glands. The intensity of IFN-gamma staining in ectopic endometrium was similar to the intensity of staining observed in menstrual and late secretory basalis samples from eutopic endometrium. CONCLUSIONS: The results of this observational study suggest that activated T cells, IFN-gamma and upregulation of antigen presentation may play a role in normal endometrial physiology. The increased number of T cells, expression of IFN-gamma, and enhanced antigen presentation in ectopic compared to eutopic endometrium support the concept that cellular immune activation is involved in endometriosis and its sequelae.

Adult↗
PubMed1982

The synthesis of prostaglandins from persistent proliferative endometrium.

The pattern of prostaglandins (PGs) synthesized by persistent proliferative endometrium of women with excessive menstrual bleeding (greater than 50 ml) associated with anovulatory cycles was compared to endometrium collected from women with normal menstrual blood loss (less than 50 ml). Levels of PGF2 alpha in normal and persistent proliferative endometrium were lower than the levels of PGF2 alpha found in normal secretory endometrium (P less than 0.005 for both normal and persistent proliferative endometria). When incubated with exogenous [1-14C]arachidonic acid (9.1 nmol), normal secretory endometrium synthesized more PGF2 alpha and PGE2 than did normal proliferative endometrium, but the amounts of PGF2 alpha and PGE2 released by persistent proliferative endometrium were similar to those obtained by normal secretory endometrium. These findings suggest that persistent proliferative and normal secretory endometria have the same PG synthetase activity, and that the low endogenous concentrations of PGF2 alpha in the former arise from a lack of endogenous precursor. PGF2 alpha has predominantly vasoconstricting properties, and a reduced capacity to synthesize this PG by persistent proliferative endometrium may result in excessive menstrual bleeding, as was suggested by the inverse correlation between the ratio of the endogenous concentrations of PGF2 alpha and PGE and the menstrual blood loss (r = -0.7; P less than 0.005; n = 26).

Adult↗
PubMed1998

Progesterone induces calcitonin gene expression in human endometrium within the putative window of implantation.

The human endometrium acquires the ability to implant the developing embryo within a specific time window that is thought to open between days 19-24 of the secretory phase of the menstrual cycle. During this period the endometrium undergoes pronounced structural and functional changes induced by the ovarian steroids, estrogen and progesterone, that prepare it to be receptive to invasion by the embryo. The identification of reliable biochemical markers to assess this critical receptive phase in the context of the natural cycle remains one of the major challenges in the study of human reproduction. Our previous studies in a rat model system demonstrated that the expression of calcitonin, a peptide hormone involved in calcium homeostasis, is transiently induced by progesterone in the glandular epithelium at the onset of implantation. Attenuation of calcitonin synthesis in the uterus during the preimplantation phase by administration of calcitonin antisense oligodeoxynucleotides severely impairs implantation of rat embryos, suggesting that this peptide hormone plays a critical role in uterine receptivity. To investigate whether calcitonin is also expressed in the human endometrium during implantation, we monitored the spatio-temporal expression of calcitonin on various days of the menstrual cycle. Our studies employing RT-PCR showed that calcitonin messenger ribonucleic acid is expressed in human endometrium during the postovulatory midsecretory phase (days 17-25) of the menstrual cycle, with maximal expression occurring between days 19-21. Very little calcitonin expression was detected in the endometrium in either the preovulatory proliferative (days 5-14) or the late secretory (days 26-28) phase. In situ hybridization and immunocytochemical analyses localized the calcitonin expression predominantly in the glandular epithelial cells of the endometrium. Our studies further showed that calcitonin expression in the human endometrium is under progesterone regulation. Treatment of women with an antiprogestin, mifepristone (RU-486), drastically reduced calcitonin expression in the endometrium. Collectively, these findings reveal that progesterone-induced expression of calcitonin in the secretory endometrium temporally coincides with the putative window of implantation in the human.

Adult↗
PubMed2007

Sonographic evaluation of the endometrium in patients with a history or an appearance of polycystic ovarian syndrome.

OBJECTIVE: The purpose of this study was to assess the incidence and significance of a thick, cystic-appearing endometrium in association with a history or an ovarian appearance of polycystic ovarian syndrome. METHODS: An Institutional Review Board-approved, retrospective medical record review of sonographic studies from January 1, 1998, to December 31, 2005, found 245 patients with clinical features, a characteristic sonographic appearance of the ovaries, hormonal abnormalities, or a history of polycystic ovarian syndrome. The sonographic thickness and appearance of the endometrium (homogeneous or heterogeneous) and histologic findings on biopsy were obtained. RESULTS: Two hundred twenty-seven patients had a homogeneous endometrium in the range of 1 to 17 mm (mean +/- SD, 6.4 +/- 3.1 mm); 18 patients had a heterogeneous endometrium in the range of 4 to 23 mm (mean, 13.2 +/- 5.6 mm). Of the 18 patients with a heterogeneous endometrium, 9 also had a sonographic finding of tiny cystic foci within the endometrium. Of these, 5 had endometrial biopsy, resulting in 2 cases of a proliferative endometrium and 1 case each of simple hyperplasia, hyperplasia with atypia, and scant tissue. No cases of hyperplasia were present in the patients with a homogeneous endometrium. CONCLUSIONS: A heterogeneous cystic endometrium is associated with the prolonged proliferative phase from chronic anovulation as well as endometrial hyperplasia.

Adolescent↗
PubMed1999

[Expression of epidermal growth factor receptor in human endometrium, decidua and trophoblast cells].

OBJECTIVE: To study the expression of epidermal growth factor receptor (EGFR) expression in human normal endometrium, decidua and trophoblast cells of early pregnancy, and to explore the effect of EGFR on cell proliferation and development. METHODS: To localize the EGFR expression in glandular and stromal cells of normal endometrium, decidua with immunohistochemical method (ABC), and to analyse the related quantity of EGFR mRNA by RT-PCR method. RESULTS: There were EGFR expression in both normal endometrium and decidua. EGFR protein located on cell membrane, nuclear membrane and in the cytoplasm as well, and located in the neuclear of glandular and stromal cells in decidua. The expression of EGFR in glandular cells was significantly stronger than that in the stroma (P < 0.05), while there was no difference of EGFR expression in the glands during the menstrual cycle (P > 0.05). However, the expression of EGFR in the glands of decidua was significantly higher than that in the proliferative and secretory endometrium (P < 0.05). The intensity of staining in stromal cells listed in order from the strongest was early decidua > secretory endometrium > proliferative endometrium, the differences were significant (P < 0.05). The related quantity of EGFR mRNA expression in proliferative, secretory endometrium, decidua and trophoblasts were: 0.531 +/- 0.061, 0.594 +/- 0.121, 0.732 +/- 0.032, 0.828 +/- 0.034, respectively. There was no difference during the menstrual cycle, but that in the decidua and trophoblasts were significantly higher than that in the proliferative and secretory endometrium (P < 0.05), and that in the trophoblasts was the highest. CONCLUSION: EGFR expression was present in the proliferative and secretory endometrium, decidua and trophoblasts of early pregnancy, and it was significantly higher in the decidua and trophoblasts than that during the menstrual cycle.

Adult↗
PubMed2000

Lymphocytes and perforin expression in endometrium during the menstrual cycle.

OBJECTIVE: To study the lymphocytes, perforin protein and mRNA expression in endometrium of different phases in the menstrual cycle and to explore the regularity and role of the lymphocytes and perforin in the reproductive system. METHODS: Immunohistochemical and in situ hybridization techniques were employed to demonstrate the population, phenotype and mediator (perforin) of lymphocytes in the proliferative and secretory endometrium. RESULTS: In different phases of the endometrium, there were very few CD3+ typical T lymphocytes, CD4+ helper lymphocytes and CD8+ suppressor/cytotoxic T lymphocytes, while CD56+ lymphocyte (also named NK-like cell) were abundant. CD56+ lymphocytes were absent in postmenopausal endometrium. A double immunohistochemical labelling method demonstrated the co-expression of perforin protein and CD56 antigen of cells in different phases of the endometrium. Quantitative analysis of CD56+ lymphocytes and perforin-positive cells increased in number from the proliferative to the secretory endometrium (P < 0.05). In situ hybridization analysis showed that perforin mRNA positive cells formed islands in proliferative endometrial stroma, but were scattered in secretory endometrium. There was difference between perforin gene expression and protein expression in the proliferative endometrium. CONCLUSIONS: Lymphocytes and perforin expression in the endometrium at different phases of the menstrual cycle are specific and may play an important role in the reproductive system. They may exert a positive influence on embryo implantation and be involved in endometrial stroma breakdown during menstruation.

Endometrium↗
PubMed1992

[The ultrasonographic characteristics of the endometrium during the spontaneous ovulatory menstrual cycle].

Six hundred and four serial transvaginal sonograms were performed in 70 normal and healthy women throughout an ovulatory cycle. The endometrium was classified in 4 types (0, 1, 2 and 3) according to: the aspect of the myometria-endometrium and endometrium-endometrium interfaces, and the texture and thickness of the functional layer. Type 0 appears as a smooth, pencil line endometrium. Type 1 has a trilaminar structure with an iso or hypoechoic functional layer. Type 2 is also trilaminar, but myometria-endometrium interfaces are thicker than type 1. Type 3 appears as a thick and homogeneously echogenic image. The relative frequency of each type of endometrium was determined for every day of the menstrual cycle. Day 0 was defined sonographically as the day of follicle rupture. Type 0 was found during and immediately after menstruation. Type 1 was seen during mid-follicular phase and until day +2. Types 2 and 3 were observed post ovulatory in 100% of the cases. The endometrium increases in thickness more during preovulatory phase (mean: 5.5 mm), than in the luteal phase (mean: 2.6 mm). We conclude that this working classification of the endometrium is useful in clinical practice when associated to the ultrasonographic aspect of the ovaries and the moment of the menstrual cycle.

Adult↗
PubMed1989

[A study on the production of CA125 antigen using tissue culture of eutopic and heterotopic endometrium].

The possibility of the endometrial production of CA125 and the effect of P4, MPA, and E2 were investigated using tissue cultures of eutopic endometrium (uterine endometrium obtained from uterine myoma) and heterotopic endometrium (uterine myometrium obtained from adenomyosis). CA125 was detected in eutopic endometrium before culture, its concentration being significantly higher in tissues obtained during the early proliferative phases than in those obtained during the early secretion. On the other hand, no significant changes in the tissue concentrations of CA125 before culture were found in heterotopic endometrium during a menstrual cycle. In the heterotopic endometrium, in the production of CA125 in the medium was higher than that in the eutopic one. The data on CA125 in the culture medium also indicated that the production was significantly higher during the proliferative phases than during secretion. Cycloheximide significantly decreased the concentrations of CA125 in the medium and in tissues of the eutopic and heterotopic endometrium. The production of CA125 was not affected by the addition of P4, but MPA significantly inhibited the in-vitro production of CA125, which could no longer be observed when E2 was simultaneously added to the medium. These results indicated that not only the eutopic but also the heterotopic endometrium could produce CA125, and this ability seems to be more marked in the heterotopic than that in the eutopic endometrium, especially during the secretory phases. This study demonstrated one of the causes of increased serum CA125 in patients with adenomyosis.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1994

Increased expression of transforming growth factor beta isoforms and basic fibroblast growth factor in complex hyperplasia and adenocarcinoma of the endometrium: evidence for paracrine and autocrine action.

Endometrial carcinoma is associated with antecedent simple and complex hyperplasia, and the endometrium is a target tissue for the action of cytokines and growth factors. Transforming growth factor (TGF)-beta s are potent cellular growth and differentiation regulatory factors. Therefore, we investigated the potential role for TGF-beta s in the normal proliferative endometrium and its possible involvement in the transition to complex hyperplasia and progression to endometrial carcinoma. The angiogenic and mitogenic growth factor, basic fibroblast growth factor, was used for comparison. Differential TGF-beta isoform-specific immunoreactivity was observed in the normal endometrium, which is composed of glandular and stromal cells. There was an increase in TGF-beta 3 but not TGF-beta 1 or TGF-beta 2 in the glandular epithelium from the proliferative to the secretory phase of the menstrual cycle. Immunostaining for TGF-beta 2 was more intense in the stroma than the glands. In contrast, TGF-beta 1 and TGF-beta 3 were near equal intensity in these two endometrial compartments, TGF-beta 3 being the most intense. The glandular epithelium demonstrated a statistically significant stepwise increase in the expression of all three TGF-beta s progressing from the normal proliferative endometrium to simple hyperplasia and on to complex hyperplasia. However, the stromal cells maintained approximately the same level of immunoreactivity for TGF-beta in all these samples. In comparing proliferative endometrium with complex hyperplasia, there was a 5.1-, 3.4-, and 2.6-fold increase in immunostaining in the glands for TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively (P < or = 0.001). There was no further increase in immunoreactivity with progression from preneoplastic complex hyperplasia to carcinoma. Immunoreactive basic fibroblast growth factor was slight in normal endometrium and simple hyperplasia. There was a 4.6- and 4.2-fold increase in immunostaining observed in complex hyperplasia compared with proliferative endometrium in the glandular (P < or = 0.0054) and stromal (P < or = 0.0053) cells, respectively, with no further increase in carcinoma. By in situ hybridization, an increase in mRNA for all TGF-beta isoforms paralleled TGF-beta immunoreactivity. However, in contrast to the increased immunostaining in the glands in complex hyperplasia, there was remarkably more mRNA in the stromal cell compartment. The discordant expression of mRNA and protein was only observed in the pathological endometrium since both were more highly expressed in the stromal cells in normal proliferative endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed2001

Production of activin A in hyperplasia and adenocarcinoma of the human endometrium.

OBJECTIVES: To examine the possible localization and production of activin A in human normal endometrium, endometrial hyperplasia, and adenocarcinoma tissues. METHODS: Human endometrial tissues were collected from 45 patients who were undergoing abdominal hysterectomy. Tissue sections were stained with monoclonal antibodies against the inhibin/activin alpha- and beta A-subunits and activin A using an avidin-biotin-peroxidase complex technique. Concentrations of activin A and inhibin A in tissue extracts of the endometrial tissues were measured using enzyme-linked immunosorbent assays (ELISAs). The expressions of the inhibin alpha-subunit and activin beta A-subunit messenger RNA (mRNA) in the endometrial tissues were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. RESULTS: No immunostaining with an antibody against the inhibin alpha-subunit was observed in human normal endometrium, endometrial hyperplasia, and adenocarcinoma. By contrast, immunostaining for the activin beta A-subunit and activin A was observed in the cytoplasm of glandular cells in normal endometrium, endometrial hyperplasia, and tumor cells of endometrial adenocarcinoma. The percentages of stained cells in endometrial adenocarcinoma were higher than those in normal endometrium. Also, the percentages of stained tumor cells with poor differentiation were higher than those with good and moderate differentiation of the endometrium. The stromal cells in normal endometrium, endometrial hyperplasia, and adenocarcinoma were weakly immunoreactive with antibodies against the beta A-subunit and activin A. Immunoreactivity of activin A in tissue extracts from normal endometrium and endometrial adenocarcinoma was detected by the two-site ELISA. Immunoreactivity of activin A was significantly higher in adenocarcinoma than in normal endometrium. On the other hand, the immunoreactive inhibin A was not detected. The expression of the alpha-subunit mRNA in endometrial tissues was demonstrated as the RT-PCR products migrated at 905 bp and the PCR products of the beta A-subunit showed a band at 366 bp. CONCLUSIONS: It is suggested that activin A, but not inhibins, are produced by endometrial tissues. The amounts of produced activin A were higher in adenocarcinoma tissues than in normal endometrium. Activin A might be involved in human endometrial tumorigenesis.

Activins↗
PubMed2004

In vivo proton magnetic resonance spectroscopy in the evaluation of the endometrium.

BACKGROUND: The purposes of this study were to compare proton magnetic resonance (MR) spectroscopic evaluation of the endometrium with histology obtained by endometrial biopsy in women undergoing diagnostic curettage and to determine whether screening with MR spectroscopy (MRS) might be useful in the evaluation of the endometrium. METHODS: Twenty-three consecutive women who were scheduled for endometrial biopsy were included in the study. The women were evaluated by MRS, performed immediately before the endometrial biopsy. The MRS results were compared with the histological findings obtained from the endometrial biopsy. RESULTS: All of the cases were proven by pathological examination, and their diagnoses were secretory endometrium (11 cases), proliferative endometrium (seven cases) and disordered proliferative endometrium (five cases). The characteristically obtained signals of choline (Cho) and lipid were detected in all subjects in the secretory endometrium group. In the same group, eight patients showed lactate signals and six showed creatine (Cr) signals. In the disordered proliferative endometrium group, four patients showed lipid plus Cho signals. Two patients in the same group demonstrated both lactate and Cr signals. All patients in the proliferative endometrium group showed Cho signals, two patients demonstrated lactate plus Cho signals, and none of the patients in this group showed lipid and Cr signals. CONCLUSION: Proton magnetic resonance spectra can register certain metabolic differences in human endometrium in its different stages.

Adult↗
PubMed1992

Platelet-activating factor stimulates phospholipase C activity in human endometrium.

Human preimplantation embryos secrete platelet-activating factor (PAF), which stimulates prostaglandin E2 synthesis from secretory endometrium. This study investigated the action of PAF on phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-specific phospholipase C activity in human endometrium. Slices of normal endometrium were incubated with 5 microCi/ml myo-[2-3H] inositol for 3 h at 37 degrees C in 95% O2 and 5% CO2 to label tissue phosphoinositides. Inositol phosphates were extracted using trichloroacetic acid precipitation and diethylether neutralization and production was measured using Dowex 1-X8 anion-exchange column chromatography. PAF induced rapid and concentration-dependent accumulation of inositol phosphates (IP) from secretory endometrium, but had no effect on endometrium removed in the proliferative phase of the menstrual cycle. The IP3 fraction was significantly elevated from a median value of 14.0 c.p.m. mg-1 dry wt [range: 8-41 c.p.m. mg-1 dry wt] to 28.0 c.p.m. mg-1 dry wt [range: 11-87 c.p.m. mg-1 dry wt, P less than 0.002] following 1 min exposure of secretory endometrium to PAF-acether, in the presence of 10 mM LiCl. PAF-induced hydrolysis of PtdIns(4,5)P2 was inhibited by the specific PAF receptor antagonist WEB 2086, in a dose-dependent manner (P less than 0.02), indicating that in human endometrium PtdIns(4,5)P2 hydrolysis is mediated via a PAF receptor. These results indicate that PAF receptor coupling activates endometrial PtdIns(4,5)P2-specific phospholipase C only in the secretory phase of the menstrual cycle, suggesting that the PAF response may be under ovarian steroid regulation. It is proposed that the ability of the endometrium to respond to PAF appears to be a feature of the preparation of this tissue for implantation and that the second messengers generated may play a role in cellular processes involved in the maternal recognition of very early human pregnancy.

Adult↗