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Localization of bradykinin type II receptor mRNA in human endometrium.

Bradykinin is a nonapeptide inflammatory agent that in the endometrium stimulates stromal cell proliferation, prostaglandin synthesis and electrogenic ion transport. The expression of bradykinin type II (B2) receptor mRNA was examined by in-situ hybridization using 35S-labelled riboprobe in human endometrium to determine its temporal and spatial pattern of distribution throughout the menstrual cycle. The B2 receptor mRNA was expressed in proliferative and secretory endometrium. In the early proliferative endometrium there were low levels of B2 receptor mRNA over both the glands and stromal cells. The signal increased in intensity and was localized over the glands with low levels of hybridization in the stroma in the late proliferative endometrium. In the early secretory endometrium B2 receptor mRNA was highly expressed in the endometrial glands. The strong hybridization signal persisted and in late secretory endometrium both glandular and stromal cells expressed B2 receptor mRNA. The apparent increase in B2 receptor mRNA in the secretory endometrium suggests that bradykinin acting via B2 receptor may play a role in the increased vascular permeability and vasodilatation associated with implantation.

Adult↗

Angiopoietin-1, angiopoietin-2 and Tie-2 expression in eutopic endometrium in advanced endometriosis.

Endometriosis is one of the most common gynaecological disorders, but its aetiology and pathogenesis remain obscure. The refluxed menstrual debris in women with endometriosis may be more prone to implantation, invasion and growth in the peritoneum or ovary through the actions of extracellular proteolysis and angiogenesis. It has been hypothesized that the endometrium from women with endometriosis has higher angiogenic activity and expresses more angiogenic factors. Using quantitative competitive PCR (QC-PCR) combined with the reverse transcription of total RNA into cDNA, we investigated the expression of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and Tie-2 in the eutopic endometrium from 56 women with severe endometriosis and that from 64 women without endometriosis during the follicular and luteal cycles. The protein expression from the eutopic endometrium was analysed by western blotting. Results were analysed statistically by Kruskal-Wallis and Mann-Whitney U tests. The eutopic endometrium from women with endometriosis expressed higher levels of mRNA and protein of Ang-1 (P < 0.05) and higher levels of mRNA of Ang-2 than the endometrium from normal women (P < 0.05). Tie-2 mRNA and protein expression from the eutopic endometrium did not differ significantly between endometriosis patients and normal controls. These results suggest that the eutopic endometrium from endometriosis patients is more angiogenic and prone to growth because of greater Ang-1 mRNA and protein expression and higher Ang-2 mRNA expression than the endometrium from women without endometriosis. Thus, increased angiogenic activity may be responsible for the pathogenesis of endometriosis.

Adult↗

Endothelial cell proliferation in the endometrium of women with menorrhagia and in women following endometrial ablation.

Local endometrial aberrations are thought to be the major contributing factor to essential menorrhagia. Here we have examined the role of endometrial angiogenesis, the growth of new blood vessels, in essential menorrhagia. Our study tested two hypotheses: firstly that angiogenesis is disturbed in the endometrium of women with menorrhagia; and secondly that when menstrual blood loss is decreased following endometrial ablation, an endometrial environment favouring normal angiogenesis has returned. Angiogenesis was measured by endothelial cell proliferation. Proliferating endothelial cells were identified by an immunohistochemical double staining technique. A total of 57 women participated in this study, of whom 19 were controls, 20 had menorrhagia and 18 were 3-6 months post-ablation. There was a significant increase in endothelial cell proliferation in the endometrium of patients with menorrhagia compared with the control endometrium. Conversely, post-ablation endometrium showed a non-significant decrease in endothelial cell proliferation. The increased endothelial cell proliferation in the endometrium of patients with menorrhagia was not the result of a general increase in endometrial cellular proliferation and did not result in a change in endothelial cell concentration compared with control endometrium. These results support the hypothesis that angiogenesis is disturbed in the endometrium of patients with menorrhagia and normalized in post-ablation endometrium.

Adult↗

Five-year follow up of women randomised to medical management or transcervical resection of the endometrium for heavy menstrual loss: clinical and quality of life outcomes.

OBJECTIVE: To assess clinical status, changes in health related quality of life, and subsequent management five years after medical management or transcervical resection of the endometrium for treatment of heavy menstrual loss. DESIGN: Five year follow up using postal questionnaires and operative databank review. SETTING: Gynaecology department of a large UK teaching hospital. POPULATION: Women referred to the gynaecologist for treatment of heavy menstrual loss. METHODS: Eligible women, without a treatment preference, were randomised equally to either medical treatment or transcervical resection of the endometrium. MAIN OUTCOME MEASURES: Women's satisfaction with treatment, menstrual status, changes in health related quality of life, and additional treatments received at five years. RESULTS: One hundred and forty-four patients completed questionnaires, achieving 77% follow up (medical n = 71/94; transcervical resection of the endometrium n = 73/93). At five-year follow up, 7/71 (10%) of those randomised to the medical arm still used medical treatment, while 72/94 (77%) had undergone surgical treatment and 17/94 (18%) a hysterectomy. Twenty-five (27%) women allocated to transcervical resection of the endometrium had undergone further surgery, 18/93 (19%) a hysterectomy. At five years women initially randomised to medical treatment were significantly less likely to be totally satisfied (P < 0.01, difference 21%, 95% CI -37% to -4%), or to recommend their allocated treatment to a friend (P < 0.001, difference 59%, 95% CI -73% to -45%). Bleeding and pain scores were similar in both groups and highly significantly reduced. Significantly more women in the transcervical resection of the endometrium arm had no bleeding or very light bleeding (P < 0.02, difference -22%, CI -31% to -4%), and they had significantly less days heavy bleeding (P < 0.02). Short Form 36 health survey scores were significantly improved from baseline for all eight health scales in the transcervical resection of the endometrium arm, and four in the medical arm. CONCLUSIONS: A policy of immediate transcervical resection of the endometrium for women referred to a gynaecologist for treatment of heavy menstrual loss achieves higher levels of satisfaction, better menstrual status, and greater improvements in health related quality of life than medical treatment. In addition, transcervical resection of the endometrium is safe and does not lead to an increase in the number of hysterectomies. An effective endometrial ablative technique should be offered to all eligible women seeking treatment of their heavy menses from a gynaecologist.

Adult↗

Effects of oestrogen on the extracellular matrix in the endometrium of postmenopausal women.

AIM: To obtain insight into the effects of oestrogen on extracellular matrix (ECM) in the postmenopausal endometrium. METHODS: The distribution of the components of the ECM, including collagen types I, III, IV, and VI, and laminin, was investigated in the human postmenopausal endometrium by an indirect immunofluorescence method with specific monoclonal antibodies and a polyclonal antibody. Collagens were also extracted from the endometrial tissues of postmenopausal women who had or had not been treated with oestrogen for three weeks. RESULTS: Immunohistochemical studies demonstrated that type I collagen was the predominant interstitial collagen, and that types III and VI collagens were absent or very sparsely distributed in the stroma of the postmenopausal endometrium. However, types I, III, and VI collagens were diffusely localised in the stroma of the postmenopausal endometrium after administration of oestrogen. Even though type IV collagen was not seen in the basement membrane of the endometrial glands in the endometrium of postmenopausal women in the absence of oestrogen treatment, both type IV collagen and laminin were localised exclusively in the basement membrane of the endometrial glands in the postmenopausal endometrium after three weeks of oestrogen treatment. The level of type III collagen relative to that of type I collagen was significantly increased (p < 0.01) in the endometrium of oestrogen treated postmenopausal women compared with non-treated postmenopausal women. CONCLUSIONS: Conjugated equine oestrogen might induce changes in the distribution of components and in the composition of the ECM in the endometrium of postmenopausal women.

Aged↗

Luteal phase concentrations of a progestagen-associated endometrial protein (PEP) in the serum of cycling women with adequate or inadequate endometrium.

We previously demonstrated that the human endometrium synthesizes and secretes a specific protein designated "Progestagen-associated Endometrial Protein" or PEP. This work was undertaken to determine luteal phase levels of PEP in serum of cycling women with histologic evidence of adequate endometrium (endometrium in phase) or inadequate endometrium (endometrium out of phase by 3-4 days). The results provide a normative curve with 95% confidence limits for serum PEP concentrations vs normalized cycle day in women with adequate endometrium (judged by histologic endometrial dating), and indicate that the PEP concentration increases exponentially after day 22, with a mean doubling time of 2.95 +/- 1.60 (mean +/- SD) days (based on serial data from 13 women). More importantly, the proportion of serum PEP values falling outside of the 95% confidence limits was significantly greater (p less than 0.001) in women with inadequate endometrium (83%) than in women with adequate endometrium (16%). Therefore, determination of PEP in serum, rather than the more invasive endometrial biopsy examination, may serve as a method of choice for evaluating endometrial adequacy in infertile women.

Endometrium↗

Differential expression of members of the bcl-2 gene family in proliferative and secretory human endometrium: glandular epithelial cell apoptosis is associated with increased expression of bax.

Glandular epithelial cells of the human endometrium initiate apoptosis in the secretory phase of the cycle. To better understand the regulation of apoptosis in this paradigm of endocrine-regulated cell turnover, we studied the expression of the cell death regulatory genes, bax, bcl-2, and bcl-x, in human proliferative and secretory endometria relative to the absence or presence of apoptosis. As assessed by immunohistochemistry, levels of BAX protein were modest in proliferative endometrium and increased dramatically in the secretory phase when apoptosis was most prevalent. Expression of BAX was predominantly localized to epithelial cells of the functionalis layer of the secretory endometrium. In contrast, BCL-2 immunoreactivity was maximal during the proliferative phase and decreased in the secretory phase. Moreover, BCL-2 was topographically concentrated in the basalis layer. Immunoreactive BCL-X protein was observed mostly in glandular epithelial cells of the human endometrium. Compared with proliferative endometrium, secretory endometrium showed stronger BCL-X staining, especially in the functionalis layer. By Western blotting we confirmed that both proliferative and secretory endometrium expressed the long or antiapoptosis form as well as the short or proapoptosis form of the BCL-X protein. Taken together, our results demonstrate a coordinated pattern of expression of bcl-2 gene family members in human endometrium during the menstrual cycle, with a shift toward greater levels of the proapoptosis protein, BAX, occurring in glandular epithelial cells during the secretory phase of the cycle. Therefore, we conclude that cyclic changes in endometrial growth and regression may be precisely regulated by shifts in the ratio or balance of BCL-2 and related proteins in glandular epithelial cells.

Apoptosis↗

Localization of interferon regulatory factor-1 (IRF-1) in nonpregnant human endometrium: expression of IRF-1 is up-regulated by prolactin during the secretory phase of the menstrual cycle.

PRL expression in the human uterus is up-regulated during the mid to late secretory phase of the menstrual cycle. This coincides with up-regulation of the expression of the PRL receptor, which is localized primarily to the endometrial glandular epithelial cells. Recent data have demonstrated activation of the Jak (Janus kinase)/Stat (signal transducer and activator of transcription) signaling pathway in the secretory endometrium after stimulation with exogenous PRL. However, the target genes for the action of PRL on the endometrial epithelial cells have not been elucidated. In this study we have investigated the pattern/site of expression of the transcription factor interferon regulatory factor-1 (IRF-1) as well as the effect of exogenous PRL on the transcription of IRF-1 in the human endometrium during the mid to late secretory phase of the menstrual cycle. Expression of the IRF-1 gene was confirmed by RNase protection assays using a 260-bp homologous [alpha-32P]UTP-labeled IRF-1 complementary ribonucleic acid (RNA) probe and 10 microg total RNA extracted from human endometrium (n = 5) collected between days 19 and 26 of the menstrual cycle. Northern and Western blot analyses were conducted on secretory phase human endometrium (n = 3) using human [alpha-32P]dCTP-labeled IRF-1 complementary DNA and antihuman IRF-1 antibody. Expression of the IRF-1 gene in the secretory phase endometrium was encoded by a RNA transcript of approximately 2.1 kb and a protein of 48 kDa. Furthermore, expression of the IRF-1 gene in the secretory phase endometrium was localized by immunohistochemistry predominantly to the glandular epithelial cells as has been shown previously for the PRL receptor. To investigate the effect of PRL on expression of IRF-1, human endometrial biopsies (n = 3) collected between days 24-26 of the menstrual cycle were cultured in the presence of cycloheximide with or without 100 ng/mL human PRL for 2 and 4 h. Culture of endometrial tissue with PRL for 2 and 4 h resulted in 2.9 +/- 0.3-fold (P < 0.01) and 1.7 +/- 0.1-fold induction of expression of the IRF-1 gene, respectively. These data demonstrate the expression of the transcription factor IRF-1 in the glandular epithelium of the endometrium and its regulation by PRL during the secretory phase of the menstrual cycle. Previous observations of the temporal up-regulation of expression of both PRL and PRL receptors in the secretory human endometrium and their localization to the stromal and glandular compartments, respectively, suggest that endometrial PRL mediates transcription of the IRF-1 gene in a paracrine fashion.

Blotting, Northern↗

Steroid receptor coactivator expression throughout the menstrual cycle in normal and abnormal endometrium.

The endometrium of reproductive aged women undergoes cyclic developmental changes in preparation for implantation in response to estrogen and progesterone. These steroids and their receptors are tightly regulated throughout the menstrual cycle, and their actions are facilitated by the presence of steroid receptor coactivators of the p160 family. In this study using immunohistochemistry and Western blot analysis, we characterize the expression patterns of three coactivators, steroid receptor coactivator-1, amplified in breast cancer-1 (AIB1), and transcriptional intermediary factor-2 in human endometrium obtained prospectively from normal fertile women throughout the menstrual cycle. With the exception of glandular AIB1, which increased in the late secretory phase, none of the coactivators changed significantly during the menstrual cycle. We compared coactivator expression patterns in fertile endometrium to the endometrium of anovulatory (proliferative; n = 3) and clomiphene-induced ovulatory (secretory; n = 13) women with polycystic ovarian syndrome (PCOS), a group that have a higher likelihood of developing estrogen-induced endometrial hyperplasia and cancer. To control for the effect of clomiphene citrate, an additional group was included consisting of ovulatory women treated with clomiphene citrate for "male factor" infertility. Compared with both fertile and infertile controls, PCOS women exhibited elevated levels of AIB1 and transcriptional intermediary factor-2 expression in both epithelial and stromal cells. We postulate that increased coactivator expression may render the endometrium more sensitive to estrogen. In support of this, we describe an increased expression of ERalpha (an estrogen-induced gene product) during the menstrual cycle in PCOS endometrium compared with fertile controls. In summary, we demonstrate that the expression of p160 coactivators are regulated in endometrium during the menstrual cycle in normal fertile women but are overexpressed in the endometrium of women with PCOS. Based on these findings, we suggest a possible mechanism to explain the poor reproductive performance observed in PCOS and the increased incidence of endometrial hyperplasia and cancer noted in this group of women.

Anovulation↗

Growth of the endometrium and cotyledons during pregnancy in the ewe: rates of protein secretion and synthesis and nuclear and cytosol steroid hormone receptor levels.

The time-course of cell hypertrophy and changes in in-vitro rates of secretion and synthesis of protein in intercaruncular and caruncular endometrium and maternal and fetal cotyledonary placenta have been examined during days 0-112 of pregnancy in the ewe. The concentrations of high-affinity receptors for oestradiol and progesterone in nuclear and cytosol fractions from these tissues were also determined. Protein secretion by intercaruncular endometrium increased 25-fold between days 0 and 84. On day 84 10(-5) M-colchicine blocked 75% of total secretion. Protein secretion did not increase in the other tissues. Protein synthesis and RNA:DNA ratio in intercaruncular endometrium increased steadily between days 0 and 112, whereas they did not change in caruncular endometrium between days 0 and 28 and declined in cotyledon between days 56 and 112. The levels of cytosol receptor for oestradiol and progesterone and of nuclear receptor for oestradiol in all tissues during days 56-112 were very low in relation to the corresponding levels in caruncular endometrium on day 0. The level of nuclear progesterone receptor in caruncular endometrium increased threefold between oestrus and day 28. The level of this receptor in cotyledon remained low on days 56-112, but in intercaruncular endometrium it increased to high values on days 84-112. The results demonstrated a major surge in secretory activity by the intercaruncular endometrium at around mid-gestation, which was associated with a marked increase in nuclear progesterone receptor levels but only a low level of nuclear oestradiol receptor. The observations do not suggest any important role for oestradiol or progesterone in the growth of fetal and maternal cotyledon.

Animals↗

Steroid hormone regulation of angiogenesis in the primate endometrium.

The human endometrium develops new capillaries from existing microvessels, i.e. angiogenesis, which then undergo maturation and remodeling, i.e. investment of microvessels with periendothelial mural cells, into a new vascular network during each menstrual cycle. Improper vascularization of the endometrium may cause implantation failure and infertility. Estrogen and progesterone have pivotal roles in establishing this vascular bed, but the cellular sites and mechanisms of action of these steroid hormones are incompletely understood. Vascular endothelial growth factor (VEGF), angiopoietin-1, and angiopoietin-2 and their receptors are expressed in the human and nonhuman primate endometrium and interact to control vascular development and remodeling. VEGF synthesis within and neovascularization of the endometrium seem to be sustained and ongoing processes designed to progressively promote growth and development of the endometrium with advancing stages of the menstrual cycle. However, estrogen rapidly upregulates VEGF expression by endometrial glandular epithelial and stromal cells in vivo in the nonhuman primate and in vitro in the human. Reports of the effects of progesterone on endometrial VEGF formation, however, are inconsistent and may reflect regulatory actions on particular isoforms of VEGF. In addition, estrogen has effects on vascular endothelial and smooth muscle cells, which may be direct or mediated by VEGF. Very little is known, however, about the steroid hormone regulation of other angiostimulatory and angioinhibitory factors, e.g. angiopoietin-1 and -2, in the endometrium. Moreover, the role of steroid hormones acting directly, or indirectly via VEGF and other angiogenic factors, on expression of integrins, cell adhesion and other molecules required for cell-cell and cell-extracellular matrix interactions important for angiogenesis in the human and nonhuman primate endometrium is largely unknown. Finally, further study is needed of cell-specific responsivity and function in the human endometrium with respect to steroid hormone regulation of angiogenesis.

Animals↗

p27, cyclin E, and CDK2 expression in normal and cancerous endometrium.

The objective was to investigate the immunohistochemical expression of p27, cyclin E, and CDK2 in normal and cancerous endometrium. Expression of p27 in premenopausal normal endometrium was significantly higher than that in postmenopausal normal endometrium (p=0.019). A significantly lower amount of p27 staining was observed in endometrial cancer tissues from premenopausal women than in normal premenopausal endometrium (p=0.015). Cyclin E expression in premenopausal normal endometrium was significantly higher than that in postmenopausal normal endometrium (p=0.003). A significantly higher amount of cyclin E staining was observed in endometrial cancer tissues from postmenopausal women than in normal postmenopausal endometrium (p=0.017). Regarding menopausal status, no significant difference in CDK2 staining was observed between cancerous and normal endometrium. There was a positive significant correlation between cyclin E and CDK2 expression levels in endometrial cancers (p<0.05). Western blot analysis confirmed elevated p27 protein levels in samples with positive p27 immunostaining. Considerable levels of p27 mRNA were detected in all normal and cancerous samples examined by semi-quantitative PCR. No significant relationship was found between telomerase activity and its association with p27 and cyclin E expression in endometrial cancers. These findings suggested that the decreased expression of p27 caused by post-translational mechanism might play an important role in endometrial cancer development in premenopausal women. In addition, increased cyclin E expression may play an important role in endometrial cancer development in postmenopausal women.

Blotting, Western↗

[Perforin protein and gene expression in the different phases of endometrium].

OBJECTIVE: To study the expression of perforin protein and gene in the different phases of endometrium and the role of perforin in the reproductive system. METHODS: Immunohistochemical and in situ hybridization techniques were employed to demonstrate the population, phenotype of the perforin positive cell in endometrum of different phases of menstrual cycle, first-trimester decidua and postmenopausal endometrium. RESULTS: Perforin positive cells were found to be located in the endometrial stroma and expressed natural killer-like cell surface marker (CD56 antigen, also named NK-like cell or CD56+ lymphocyte). The quantitative analysis of perforin protein cells demonstrated an increase in number from proliferative endometrium to secretory endometrium through first-trimester decidua (P < 0.05). These cells were absent in the postmenopausal endometrium. Perforin mRNA positive cells formed islands in proliferative endometrium stroma, but the perforin protein expression cells were scattered. There was difference between the perforin gene expression and protein expression in proliferative endometrium. In first-trimester decidua, perforin mRNA positive cells incresed. Some perforin mRNA positive cells located around spiral arterioles were observed. CONCLUSIONS: Expression of perforin in the different phases of endometrium is specific and plays an important role in the reproductive function. They probably exert some influence on embryo implantation and may be involved in endometrial stromal breakdown during menstruation.

Adult↗

Estimation of neovascularisation in hyperplasia and carcinoma of endometrium using a "power" angio-Doppler technique.

The aim of this study was to estimate neovascularisation in hyperplasia and carcinoma of the endometrium using a "power" angio-Doppler technique. One hundred and eighty-two postmenopausal patients with irregular bleeding from the sexual organs were investigated. Age of the patients ranged between 46 and 78 years. No neovascularisation in a control group of women with normal histopathological results of the endometrium was observed. The sensitivity of this method with reference to the diagnosis of hyperplasia and cancer of the endometrium was 12.2% and 81.2%, respectively. The specificity and positive prediction values were equal to 100% each in both pathologies. The values of the analysed flow indices in the neovascular arteries in endometrial cancer were significantly lower (p<0.05) (properly PI-0.92+/-0.12; RI-0.46+/-0.08) in comparison to the corresponding values in hyperplasia of the endometrium (PI-1.38+/-0.28 and RI-0.66+/-0.18). In conclusion, using a "power" angio-Doppler technique irregular vascularity of the endometrium in a group of patients with hyperplasia was observed in 12.2% of all patients and in 81.2% of those with cancer of the endometrium. The analysis of the values of the blood flow qualitative parameters in the neovascularisation areas in the endometrium at the significance level of PI < or = 1.0; RI < or = 0.5 and TAMV > 18.0 cm can help determine the essential element in the differential diagnosis of benign and malicious lesions. Transvaginal ultrasonography with a "power" angio-Doppler technique can be a valuable diagnostic method in hyperplasia and cancer of the endometrium, especially useful in the early stages of these pathologies.

Adenocarcinoma↗

[Expression of midkine in eutopic and ectopic endometrium of patients with severe endometriosis and its clinical significance].

OBJECTIVE: To investigate the expression of midkine (MK) in eutopic and ectopic endometrium of patients with severe endometriosis and its clinical significance. METHODS: Immunohistochemical streptavidin-biotin peroxidase (SP) method was used to detect MK expression and microvessel density (MVD) in eutopic and ectopic endometrium. Specimens of eutopic and ectopic endometrium were collected from 41 patients with serious endometriosis (study group) and 32 patients with uterine fibroid (control group). RESULTS: The positive rate of MK expression in the eutopic endometrium from study group was 63% (26/41). It was significantly higher than that in the ectopic endometrium from study group was 29% (12/41) and the eutopic endometrium from control group was 22% (7/32, P < 0.05). MK expression was positively correlated to microvessel density (r = 0.637, P < 0.05). CONCLUSION: Over-expression of MK protein is showed in the eutopic endometrium of patients with severe endometriosis and correlated to endometriotic angiogenesis. The change of MK expression in eutopic endometrium may be related to the pathogenesis of severe endometriosis.

Adult↗

[Expression and significance of gonadotropin-releasing hormone receptor in the endometrium of normal and endometrial cancer uterus].

OBJECTIVE: To investigate the expression of gonadotropin-releasing hormone receptor (GnRH-R) mRNA in the endometrium of normal and endometrial cancer uterus. METHODS: In situ hybridization was used to detect the expression of GnRH-R mRNA in 23 cases of normal endometrium in hyperplasic phase, 30 cases of normal endometrium in secretory phase, and 30 cases of endometrium from endometrial cancer. RESULTS: The results showed that GnRH-R mRNA was expressed in the cytoplasm of endometrium of normal and endometrial cancer uterus. There was no expression in the nuclei. There was no significant difference (P > 0.05) in the expression rate between the hyperplasic phase (17%, 4/23) and the secretory phase (17%, 5/30) in normal uterus. The expression rate in endometrial cancer was 40% (12/30), which was significantly higher than normal endometrium (P < 0.05). CONCLUSIONS: The data demonstrates that GnRH may act directly on endometrium. GnRH-R is highly expressed in the endometrium of endometrial cancer.

Adenocarcinoma↗

Insulin-like growth factor I receptors in normal and neoplastic human endometrium.

Insulin-like growth factor I (IGF-I) binding sites were characterized in normal and neoplastic endometrium. The characteristics of the endometrial IGF-I receptor are similar to those reported for other tissues. The binding of 125I-IGF-I to the endometrial membranes is saturable and time, temperature, and pH dependent. The 125I-IGF-I binding activity to the membranes obtained from differentiated and undifferentiated adenocarcinoma as well as sarcoma of the endometrium was significantly higher (P less than 0.05) when compared to the binding activity of the membranes obtained from normal endometrium. The Scatchard analysis of the competitive binding data of both normal and neoplastic endometrium revealed linear plots. This indicated a single class binding site for IGF-I with equilibrium dissociation constants (Kd) of 5.0, 6.8, 6.94, and 6.88 nM for normal, differentiated, and undifferentiated adenocarcinoma, and sarcoma of the endometrium, respectively. Therefore, the differences observed in 125I-IGF-I binding between normal and neoplastic endometrial membranes was due to an increase in the number of IGF-I binding sites and not to a change in receptor binding affinity. Autoradiograms from affinity labelling studies revealed a band corresponding to Mr 132,000 subunit of the receptor which is characteristic of the type I receptor reported for other tissues. A dimer of the alpha subunit (Mr 263,000) was also observed in all four categories of endometrial tissue. Additionally, autoradiograms obtained from sarcoma of the endometrium revealed a Mr 40,000 band that was only displaced by IGF-I and IGF-II peptides but not by the monoclonal antibody alpha IR-3 to the type I receptor. These suggest that the band is representative of the IGF-I or IGF-II binding protein. A similar band was not observed in the other tissues. The results show that the human endometrium contains high affinity IGF-I or IGF-II binding sites. The fact that IGF-I binding activity was significantly higher for neoplastic endometrium suggests that IGF-I may play an important role on supporting the growth of this neoplastic tissue.

Affinity Labels↗

[Variability of the thickness of the endometrium in sheep under the intravaginal effect of chlorsuperlutin].

Variability of the endometrium thickness and surface epithelium in sheep after the effect of 20 mg of chlorsuperlutin (vaginal swabs soaked in this preparation) was studied. The results obtained demonstrate that at the estrus synchronization by means of the above mentioned preparation similar changes of the endometrium can be observed as those at the estrus without controlled sexual activity. It was found out that the variability of the endometrium thickness, both in cows and heifers, depended on the follicle-stimulating hormone evoking mucosal edematization in view of the phase of the cycle when the ovulation-inhibiting factor came into play. The endometrium thickness of 1499.5 mu on an average was found in sheep with synchronized estrus, and the epithelium thickness was, on an average, 24.7 mu. We observed, according to the results of the experiment, that the endometrium thickness varied even in a given animal; the changes were the same on the endometrium of both horns of uterus independent of the ovary showing cyclical changes. The endometrium gets thinner towards to oviduct, its thickness not being uniform in individual parts of uterus. The results can be distorted due to some artificial factors, e.g. the way of sampling, fixating media, etc. Nevertheless, an assessment of the variability of the endometrium thickness belongs to objective methods to examine the functional activity of ovaries and to find out the state of uterine mucosa.

Animals↗