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Glycogen estimation by a rapid enzymic method in very small samples of human endometrium: glycogen content in the endometrium of infertile patients during the menstrual cycle.

An enzymic method using alpha-glucosidases was adapted for measuring glycogen in very small samples (3 mg) of human endometrium. The method is useful as a clinical test of the physiologic function of human endometrium. The glycogen content of the endometrium of normal and infertile patients was measured during the menstrual cycle. The maximal content in both groups was observed between the 16th and 23rd days of the cycle, but the glycogen content of the infertile group was significantly lower (P less than 0.005). These results confirm the reports of others. Endometrial glycogen and urinary pregnanediol levels in 32 infertile patients were measured on day 7 after ovulation. The glycogen content of the endometrium of 21 of these patients, who showed normal excretion of urinary pregnanediol (greater than or equal to 2 mg/day), was significantly higher than that of the other 11 patients who showed low excretion of urinary pregnanediol (less than 2 mg/day) (P less than 0.005). This finding suggests that there is a high correlation between the function of the corpus luteum and endometrial glycogen deposition.

Clinical Enzyme Tests

[Progesterone-induced changes of the endometrium and cervix mucosa in glandular, cystic hyperplasia of the endometrium].

In a period of 5 years 116 specimens were collected with various techniques from patients with the homologous type of cystic-glandular hyperplasia of the endometrium. These were systematically studied with a view to identifying a potential progesteron effect on the morphology of the endometrial and, given sufficient material, cervical mucosa. While the endometrium was examined for discrete areas with signs of secretion, attention in cervical specimens was directed to the potential presence of focal alveolar proliferations of cervical glands with basal cell hyperplasia (socalled cribriform polypoid hyperplasia). Progesteron-induced changes of major endometrial areas were found to be present in 6,9% of cases; the "cribriform polypoid hyperplasia" involving the cervical mucosa was seen in 9 of 43 cases (20,9%) with adequate cervical specimens. In 2 of the patients with progesterone-induced cervical changes luteinized follicular epithelium in the ovaries was indicative of effective endocrine activity. The different action of progesterone on the endometrial versus the cervical mucosa is discussed on the basis of katamnestic studies.

Adult

[The hyperplasia forms of the endometrium and their correlations to the endometrium carcinoma (author's transl)].

In cases of endometrial carcinoma where hysterectomy was performed, we examined histologically the marginal endometrium. For comparison we formed a control group of women of the same age. In the age between 45 and 65 adenomatous hyperplasia in the cancer group is found significantly more often. The glandular-cystic hyperplasia is found more frequently in the age group beyond 55, especially in women beyond 65. The simultaneous incidence of adenomatous hyperplasia and endometrial carcinoma suggests this form of hyperplasia being precancerous. Before the menopause the glandular-cystic hyperplasia does not seem essential for the origin of the endometrial cancer. It is not yet known why the glandular-cystic hyperplasia is found more frequently in postmenopausal women with endometrial carcinoma. The role of the estrogenic hormones as agents possibly forming a good terrain for the endometrial cancer is discussed.

Aged

[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

Histology of the baboon endometrium during the menstrual cycle and pregnancy.

The histologic characteristics of baboon endometrium during the menstrual cycle and pregnancy were studied and compared with those of human endometrium. Eight phases of endometrial change during the menstrual cycle are described. The samples were dated on the basis of sex skin changes. The basic histology of the baboon endometrium is similar to that of human endometrium, but some differences were observed. The growth of baboon endometrium is more sluggish, secretion is less intense, and many of the changes, especially in the stroma, are localized, less diffuse than they are in human endometrium. During pregnancy, decidual transformation in the baboon is much less intense than that in the human. No differences were observed between endometrium in association with preimplantation embryos and that from nonpregnant animals at comparable times following ovulation.

Animals

Ultrastructural features in normal and hyperplastic postmenopausal endometrium.

Seven samples of postmenopausal endometrium were studied by electron microscopy. Four samples were diagnosed as adenomatous hyperplasia (2 of which were atypical) and 3 as normal postmenopausal endometrium. The most striking ultrastructural features of hyperplastic endometrium were: numerous nucleoli, deep nuclear membrane infoldings, increased nucleocytoplasmic ratio, prominent and enlarged RER closely associated with mitochondria and nuclear membrane, abundant free ribosomes and marked network microfilaments. In the case of atypical adenomatous hyperplasia, the protruded intraglandular proliferating epithelial cells exhibited more atypical features than the epithelial cells of the glandular lining, suggesting a more advanced degree of anaplastic change. The characteristic features of the normal postmenopausal endometrium were: paucity and random distribution of the cytoplasmic organelles, the presence of large cytoplasmic vacuoles and short, blunt microvilli. Secretory vacuoles opening into the lumen of the gland were found in one case of cystic atrophy of a normal postmenopausal endometrium. Collagenization was found in the stroma of both groups, although predominantly in the normal postmenopausal endometrium. In 2 cases of adenomatous hyperplasia stromal cells with vacular cytoplasm were found. The significance of these findings, as related to their importance as precursor stages of endometrial cancer (in the cases of adenomatous and atypical adenomatous hyperplasia); as involutional manifestations (in the cases of normal postmenopausal endometrium); and as related to the absence of cyclic activity (in both groups) is briefly discussed.

Cell Nucleus

Characterization and comparison of receptors for 17 beta-estradiol and progesterone in human proliferative endometrium and endometrial carcinoma.

Sedimentation coefficients of cytoplasmic estradiol and progesterone receptors of human proliferative endometrium and endometrial carcinoma were determined by sucrose gradient centrifugation. In the absence of KCl, receptors from proliferative endometrium sedimented as single bands in the 8 S region and in the presence of 0.3M KCl in the 4 S region of the gradients. Receptors from endometrial carcinoma sedimented in several bands (between 3 and 9 S). When chromatographed on agarose gel comumns, the receptors (from both normal and neoplastic tissue) showed different molecular weights in the presence and absence of KCl (approximately 40,000 and 120,000, respectively). Elution profiles from agarose gel and ion exchange columns, as well as electrophoretic patterns from isoelectric focusing, revealed a similarity between biochemical properties of the receptors from endometrial carcinoma and proliferative endometrium. While the concentration of binding sites for estradiol and progesterone in normal endometrium depended on the day of the cycle, in endometrial carcinoma it depended on the degree of differentiation of the tumor. The binding of estradiol was highest at the beginning of the proliferative phase and declined continuously towards the 14th day of the cycle. In contrast, the concentration of progesterone binding sites was relatively low throughout the proliferative phase. In endometrial carcinoma low binding of estradiol was obtained in well differentiated tumors and high binding (as high as in proliferative endometrium) in undifferentiated tumors. For progesterone the contrary was the case. There was no difference in pH sensitivity between cytoplasmic receptors from normal and neoplastic tissue, optimal binding occurring at pH 7. Dissociation constants (Kd) for estradiol and progesterone depended on the degree of tumor differentiation. Kd values increased for E2 and decreased for P with increasing differentiation of the tumor. Competition studies with various unlabeled steroids revealed no significant difference between the specificity of the receptors from proliverative and neoplastic endometrium.

Binding, Competitive

An ultrastructural comparison of human endometrial adenocarcinoma with normal postmenopausal endometrium.

Although electron microscopy has been of limited value in detecting malignant neoplasms, some neoplasms do exhibit characteristic ultrastructural features. Intensive study of these features may offer insight into the etiology and activity of such tumors. In an attempt to characterize the ultrastructure of endometrial adenocarcinoma, tissue was examined with the electron microscope and compared with normal postmenopausal endometrium. Endometria from biopsy, hysterectomy, or curettage were processed routinely for light and electron microscopy. Several ultrastructural features of the adenocarcinoma were common both to previous descriptions of endometrium of the postovulatory phase and to the normal postmenopausal endometrium, described here, viz, atypical mitochondrial forms and cell surface modifications. Ribosomes were abundant in adenocarcinoma of the endometrium, normal postmenopausal endometrium, and normal cyclic endometrium in the preovulatory phase.

Adenocarcinoma

[Sex hormone regulation of progesterone and estradiol receptors in the cytosol of human endometrium in normal and pathologic pregnancy].

Hormonal control of progesterone and estradiol receptors was studied in the cytozol of short-lived culture of human endometrium in normal and undeveloping pregnancy. Endometrium was cultivated in the presence of estradiol or progesterone for 16 hours. In cultivation of normal endometrium with estradiol the content of estradiol receptors increased 4-fold in comparison with unstimulated tissue, and of progesteron receptors--3-fold. In cultivation of normal endometrium with progesterone the content of estradiol receptors rose 4--5-fold, and of progesterone receptors--3-fold. In cultivation of pathological endometrium with estradiol or progesterone the number of estradiol receptors was only doubled, and of progesterone receptors--increased only 1 1/2 times, this pointing to a diminished sensitivity of pathological endometrium to the regulating action of sex hormones.

Cells, Cultured

Clear cell carcinoma of the endometrium.

The clinical data of 22 patients with clear cell adenocarcinoma of the endometrium treated at the University of North Carolina Memorial Hospital are reported. In addition, the data with particular reference to survival, site of recurrence, and treatment are combined with information from two previous reports of clear cell adenocarcinoma of the endometrium to better define survival. It is noted that the patients with clear cell adenocarcinoma of the endometrium were older and had an overall poorer survival than is reported for adenocarcinoma of the endometrium (nonclear cell). Patients with Stage I clear cell carcinoma of the endometrium, however, had a similar five-year survival to Stage I adenocarcinoma of the endometrium. The paper also examines treatment methods and correlates these with site of recurrence as well as survival.

Adenocarcinoma

[The treatment of pre-malignant hyperplasias of the endometrium with progesterone-carrying intra-uterine devices (author's transl)].

The local administration of progestional agents for the treatment of adenomatous hyperplasia of the endometrium is insufficient for two reasons: 1. The locally applied progestational agent does not reach the total surface of the endometrium especially not in the uterine fundus or in the tubal cornua. This is frequently due to uterine myomata and to the T-shape of the intra-uterine device which does not contain progestational agents within the T. 2. The progestational agent released by the intra-uterine device does not reach the deeper layers of the endometrium. It is therefore possible that the deeper layers of the endometrium undergo malignant change. At present it is therefore necessary to administer progestational agents in the treatment of adenotamous hyperplasias of the endometrium systemically.

Endometrial Hyperplasia

[The diagnostic reliability of the jet-wash technique with regard to the diagnostic of endometrium carcinoma (author's transl)].

The jet-wash technique is an efficient method for diagnosing the endometrium carcinoma. Among 750 women we detected 50 endometrium carcinomata all of which were diagnosed by the jet-wash method. Wrongly positive findings do not exist in our series of examinations. Of the pre-stages of the endometrium carcinoma, such as adenomatous hyperplasia and adenocarcinoma in situ, however, only scarcely 50 per cent of all cases were diagnosed. The jet-wash method is also suited for outpatient clinics. Thus, patients with risk-factors for the endometrium carcinoma might be controlled annually once in outpatient clinics in addition to the usual cancer prophylactic examinations. Above all, we consider 1. patients suffering from bleeding anomalies as from the 40th year of age, 2. patients free from any symptoms, but suffering from obesity, hypertension and diabetes mellitus, 3. patients with an increased narcosis risk, 4. patients of the perimeno-pause prior to an estrogen treatment and 5. cancer post-care patients suffering from a primarily radiated endometrium carcinoma. The direct smears and the cytocentrifuge preparations can be diagnosed right on the day of examination. The thrombin cell block technique requires more work for a cytological laboratory. For a histological laboratory it might not mean any additional essential burden.

Biopsy

Immunoglobulins and secretory component in endometrium and cervix. Influence of inflammation and carcinoma.

The synthesis of immunoglobulins and secretory component in the cervix and the endometrium was studied by tissue culture and immunofluorescence. Out of the 75 cervical biopsies studied, 17 were epidermoid carcinomas, 8 were carcinomas in situ and 23 tissues had inflammatory or metaplastic lesions. A total of 49 samples from endometrium were studied, out of which 22 were in the proliferative phase, 17 were in the secretory phase and 4 were carcinomas. In the cervical tissues without lesions, there were very few plasmacytes, the synthesis of immunoglobulins was low and in 66% of the tissues the synthesis of IgG was equal to or higher than that of IgA. With local modifications, the IgG synthesis was even more preponderant and was very important in epidermoid carcinomas which were infiltrated with numerous IgG plasmacytes. Secretory component was synthesized by almost all the tissues except the epidermoid carcinomas. The endometrium did not synthesize immunoglobulins; secretory component was synthesized only by endometrial tissue in the secretory phase and by 2 of the 4 carcinomas studied. It seems that in the cervix and the endometrium there is no relationship between the production of secretory component and the presence of IgA plasmacytes which probably localise as a result of other influences. The conditions in which the local secretory immunological system would react preferentially remain to be determined.

Autoradiography

[The histological reaction of the endometrium to gestagens applied locally].

To study the histologic changes produced by a new type of progesterone-medicated intrauterine device we examined the endometria of six hysterectomy specimens and one complete curettage. After being in place for 1 month the device induced a mild perifocal "arrested secretion" of the upper layers of the endometrium; after 3 months the change was pronounced, with decidually transformed stromal cells and atrophic glands. After 12 months these changes had partially progressed to fibrous atrophy. The endometrium underlying the perifocal-arrested secretion showed either proliferative or secretory changes almost like those of the lower functionalis of a normal menstrual cycle. A generalized atrophy of glands developed only when the patient had used oral contraceptive agents before the device was inserted. The perifocal arrested secretion thus differs from the generalized arrested secretion of the endometrium that follows use of oral or injected gestagens and from the decidualization produced mechanically by the local effect of an intrauterine device. The contraceptive effectiveness of the medicated intrauterine device, as compared with that of a simple device, is increased by the glandular atrophy of the arrested secretion. It avoids the dangers of the generalized effects of progestational agents by limiting the changes to the upper layers of the endometrium which are so important for implantation.

Administration, Topical

The ultrastructural response of human endometrium to medroxyprogesterone acetate.

Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage.

Adult

Proliferation kinetics of human endometrium during the normal menstrual cycle.

A radioautographic analysis of the number and distribution of labeled nuclei after in vitro incorporation of radiothymidine was carried out in human endometrium during the normal menstrual cycle. The highest rates of proliferation were recorded on cycle days 8 to 10 in the upper one third of the functionalis layer. Coinciding with intraglandular secretory activity on cycle day 19, the rate of proliferation of gland cells decreased near zero levels and remained unchanged thereafter. Midsecretory phase arteriolar coiling and stromal predecidualization were associated with increased isotope incorporation. DNA synthesis in premenstrual endometrium was limited to the surface epithelium, predecidua, and vascular endothelium. The endometrium of the isthmus and cornual regions and of the basalis zone demonstrated relatively constant and comparatively lower rates of proliferation throughout the cycle. Regional and cellular variations in nucleic acid synthesis in cyclic endometrium are likely to reflect differences in physiologic functions in target cells in response to cyclic hormonal stimuli.

Adult

Prolactin production by human endometrium during the normal menstrual cycle.

Prolactin (PRL) synthesis by human decidua from term pregnancies has been reported. The present study examined the tissue content and in vitro production of prolactin by "decidualized" and "nondecidualized" endometrium unassociated with pregnancy. Tissue obtained throughout the menstrual cycle was dated histologically. When proliferative endometrium (N = 16) or secretory endometrium prior to day 22 (N = 6) was examined, no PRL was detected in the tissue or medium after a 24-hour incubation at 37 degrees C in Gey's buffer. Total PRL in tissue and medium measured by radioimmunoassay increased significantly from 1.2 +/- 0.3 ng/100 mg of tissue at cycle days 22 to 24 (N = 4) to 5.3 +/- 2.4 ng/100 mg of tissue at cycle days 25 to 26 (N = 7). The addition of 100 micrograms/ml of cycloheximide to the medium prevented the net increase in PRL content during incubation. It is concluded that PRL is synthesized by endometrium during the normal menstrual cycle and that the appearance and degree of synthesis and decidualization of the stroma correspond.

Cycloheximide