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Introduction: Stereotactic radiosurgery is one of the main treatments for vestibular schwannomas (VS). Their feature is frequent post-radiation pseudoprogression. This may be due to hormonal status of patients., Objective: To analyze expression of progesterone and estrogen receptors in women and men with VS., Material and Methods: Immunohistochemical analysis of expression of progesterone (PR) and estrogen receptors (ER) after biopsy was performed in 240 patients with VS between 2018 and 2021. ER/PR expression was assessed in men ( n =120) and women ( n =120) in 3 age subgroups: young age (18-44 years), middle age (45-59 years) and old age (60-79 years). Each subgroup included 40 patients. Statistical analysis was performed using the Mann-Whitney test and MedCalc software., Results: ER expression is not typical for VS (men - 1 (0.01%), women - 3 (2.5%)). At the same time, PR expression was found in 29 (24.2%) men and 21 (17.5%) women. We found no significant difference in expression of ER and PR between men and women. However, variability in PR expression was revealed, i.e. predominance of this indicator in young women ( p =0.0463) and middle-aged men ( p =0.0110). Expression of PR was similar in elderly patients ( p =0.2382)., Conclusion: The established incidence of PR expression may be one of the probable causes affecting development and duration of VS pseudoprogression after radiosurgery without clear relationship between sex and age. Further prospective research is needed to predict the risks of pseudoprogression.

Updated 2023 guidelines from the College of American Pathologists (CAP) on immunohistochemical detection of human epidermal growth factor receptor type 2 (HER2), receptors of estrogen (ER) and progesterone (PgR), and the cell proliferation marker Ki-67 in breast cancer are presented. Attention is drawn to the emergence of two new terms «ER Low Positive» and «HER2 Low» to characterize tumors with low expression of estrogen receptors and HER2.

Background. Benign ovarian tumors (BOT) occupy the 2 nd place in the structure of diseases of the female genital organs. In 20% of women of reproductive age, BOT are associated with infertility. One of the causes of infertility caused by ovarian tumors is morphofunctional inferiority with impaired endometrial receptivity., Objective: To reveal the morphological and functional features of the endometrium and the level of receptivity to sex hormones in patients with BOT before and after organ-preserving operations., Material and Methods: The study included 77 patients with epithelial ovarian tumors (EOT) - I group, 52 with mature teratomas (MT) - II group. Before and 6-12 months after laparoscopic cystectomy aspiration biopsy of endometrium was performed in the middle stage of secretory phase. The percentage and degree of maturity of pinopodes were determined, and the level of expression of estrogen (ER) and progesterone (PR) receptors in the glands and stroma of the endometrium was assessed., Results: At the preoperative stage, a decrease in the number of mature pinopodes in patients with EOT was revealed. Normal levels of ER were determined in glands and stroma of endometrium, PR was reduced both in stroma and glands of uterine mucosa. In patients with MT all markers corresponded to those of healthy women. In the postoperative period an increase in the number of developed pinopodes on the apical surface of endometrium in patients of I group was found. The ER level did not differ from control values, PR remained reduced in stroma. In II group a persistent decrease in quantity of mature pinopodes, ER in stroma, PR in glands and stroma of uterine mucosa was recorded., Conclusion: The presence of BOT and unintentional intraoperative removal of healthy ovarian tissue lead to indirect disorders of the morphofunctional state and endometrial receptivity.

Aim: to investigate the molecular mechanisms and morphological substrate of reduced uterine leiomyoma in patients receiving the selective progesterone receptor modulator (SPRM) ulipristal acetate for 3 months, by estimating the immunohistochemical expression of the markers steroid receptor coactivator 1 (SRC-1), nuclear receptor corepressor 1 (NCoR-1), ER, PgR, Ki-67, p16, TGF-β, and VEGF in tumor tissue., Subjects and Methods: The investigation enrolled 75 women with uterine leiomyoma, menorrhagias, and anemia. Group 1 included 40 patients who were treated with ulipristal for 3 months, followed by laparoscopic myomectomy. Group 2 consisted of 35 patients who underwent surgery without previous preparation. The intra- and postoperative parameters and molecular and morphological changes in the myomatous nodules were comparatively analyzed in both groups., Results: After 3 months of therapy initiation, menorrhagia completely ceased, myomatous nodules decreased in size (p<0.05), hemoglobin levels were elevated (p<0.01), and total intraoperative blood loss and operative time decreased in all the patients in Group 1. The morphological substrate of partial leiomyoma reduction was leiomyocyte apoptosis and dystrophy, tumor stroma sclerosis and hyalinosis with diminished Ki-67 expression and elevated p16 in the smooth muscle cells, trophic nodular tissue disorders exhibited by vascular wall sclerosis and lower VEGF and TGF-β expression, and leiomyocyte hormonal reception dysregulation that made itself evident through the reduced expression of SRC-1 with the unchanged expression of PR and ER and the maintained level of NCoR-1., Conclusion: The molecular mechanisms of tumor reduction involved the reduced Ki-67 expression and elevated p16, lower VEGF and TGF-β, diminished SRC-1 expression with the maintained level of PR, ER, and NCoR-1. Overall, this is suggestive of enhanced apoptosis and reduced leiomyoma proliferation and angiogenesis induced by SPRM and indicative of the expediency of using ulipristal acetate as a preoperative agent for organ-sparing surgery in reproductive-aged patients with uterine myoma, menorrhagias, and anemia.

Currently, no molecular biological markers do exist for early diagnosis of breast cancer. One of the possible candidates for the marker of early breast cancer is mammaglobin (MGB1) or SCGB2A2 (secretoglobin, family 2A, member 2), characterized by the maximal expression level in early breast cancer. Using the RT-PCR method MGB1 mRNA expression was examined in 57 tumor tissue samples and 57 samples of morphologically non-malignant tissue (MNT) of breast cancer (BC) patients. Specificity and sensitivity of the MGB1 mRNA assay in peripheral blood of BC patients was evaluated by nested PCR. 169 blood samples (from 95 BC patients, 22 from patients with benign breast tumors, 28 from patients with tumors of other localizations, and 24 samples from healthy donors) have been analyzed. MGB1 expression was significantly higher in BC tissue samples compared to MNT (p=0.0019). The maximal expression level was in the samples T1 (p=0.013), stage I BC (p=0.037), GI (p=0.0019). The MGB1 expression positively correlated with expression of estrogen (p = 0,034) and progesterone (p=0.0004) receptors. Sensitivity and specificity of the MGB1 mRNA assay in peripheral blood were 60.6% and 92.3%, respectively. Expression of MGB1 was higher in BC than MNT and it decreased during BC progression. The sensitivity and specificity of the MGB1 mRNA assay may be used as an additional diagnostic method.

The cytotoxic activity of synthetic progestins (pregna-D'-pentaranes) II-V full agonists of the progesterone receptor (PR) for PR-positive and PR-negative cells of human breast carcinoma was studied. These compounds were more active in the PR-positive MCF-7 cells than in the PR-negative MDA-MB-453 cells. Cytotoxic effects of tested compounds against normal epithelial MDCK cells were not found. Molecular modeling of studied steroids with PR showed that all progestins with close energy values can bind to the ligand binding domain (LBD) of PR and the magnitude of the energy exceeds the value estimated for the progesterone molecule. Thus, the studied progestins are active against different molecular subtypes of breast cancer and represent a promising class of chemical compounds for oncology.

Progesterone and its analogs may exert opposite effects on cell proliferation, apoptosis, and epithelial-mesenchymal transition, leading to higher cell motility and metastasis. Their ultimate effect is determined by a number of factors: the structure and concentration of the steroid, its affinity for various forms of steroid hormone receptors, activation of nongenomic mechanisms, the composition and proportion of different progesterone receptors and sensors, activity of various signaling pathways, the set of transcription factor coregulators, DNA accessibility in chromatin, activity of steroid-metabolizing enzymes, intercellular interactions within tissues, the hormonal status of the body, disease stage, and species-specific features. The review considers the factors that determine the role progestins play in proliferation and apoptosis of human tumor cells of various origins.

The concurrence of undifferentiated connective tissue dysplasia (uCTD) and hereditary thrombophilia (HT) often accompanies female infertility, in the pathogenesis of which impaired endometrial receptivity plays an important role., Aim: to investigate endometrial morphological and immunophenotypic features in patients with primary infertility in the presence of uCTD and HT., Material and Methods: The pipelle endometrial biopsy specimens taken in the implantation window were examined in 81 patients, including 13 women with a clinical diagnosis of uCTD, 40 with HT, 19 with uCTD concurrent with HT, and in a control group of 9 heathy surrogate mothers. Morphological, immunohistochemical, and morphometric examinations were done to study the paraffin-embedded endometrial biopsy sections stained with hematoxylin and eosin, pikrofuksin by van Gieson, and with toluidine blue. Immunohistochemical tests were carried out using primary antibodies against ER, PgR, LIF, PAI-1, VEGF, Collagen I, Collagen III, fibronectin, laminin, MMP-2, and MMP-9., Results: The uCTD, HT, and uCTD + HT groups were found to have signs of decreased endometrial receptivity as dramatically lower counts of mature pinopodes, slower endometrial maturation, reduced expression of the receptivity marker LIF, and deviations of the stromal progesterone-estrogen index from the normal value. Sclerotic foci with type III collagen accumulation were detected in the endometrial stroma., Conclusion: uCTD and HT and especially their concurrence are commonly a concomitant disease and risk factors for infertility in women due to impaired endometrial receptivity. In uCTD, connective tissue remodeling processes are substantially retarded, which ultimately leads to increased processes of endometrial stromal sclerosis, reduced endometrial receptivity, and infertility. The most pronounced morphological and immunophenotypical changes have been ascertained to develop in the uCTD + NT group. The findings may be used to predict and devise new infertility treatments in patients with uCTD + NT.

The study was carried out to evaluate clinical informativeness ofstudies of immunological parameters of structural and functional elements of endometrium in complex with profile of embritropic autoimmune antibodies under non-carrying of pregnancy The sampling consisted of 19 women of reproductive age with episodes of non-carrying in first semester. They were examined for inherited thrombophilia and profiles of immune reactivity of natural regulatory auto-antibodies (ELI-P-Complex). The biopsy material of endometrium was subjected to histological and immune histochemical (CD16, CD56, CD68, CB138, estrogen and progesterone receptors) analyses. In women with non-carrying of pregnancy polyclonal immunosuppression, increased level of embriotoxic auto antibodies to Fc- fragment of immunoglobulin, insulin and thyroglobulin are detected. The immune histochemical analysis established expressed decreasing of amount of progesterone receptors of stromal elements of endometrium after spontaneous abortion. The activation of killer activity of decidual lymphocytes under habitual non-carrying of pregnancy was detected too. The positive dependency was established between: expression of progesterone receptors in glandular cells of endometrium and level of anti-spermatic antibodies in blood serum; expression of progesterone receptors in stroma and level of antibodies to human chorial gonadotropin; expression of receptors of estrogens in stroma and level of antibodies to Fc-fragment of immmunoglobulines. The study data permits affirming that evaluation of level of regulatory auto-antibodies is informative at examination of woman after episode of non-carrying of pregnancy. The production of antibodies has direct relationship with pathological processes in endometrium and it can be one of criteria of completeness of pre-conceptional preparation.

The review considers the effect of progestins on the function, proliferation, and apoptosis of cells of various organs in health and noncancerous disorders. Data are summarized to describe the mechanism of progestin action through various progesterone receptors and sensors and the regulation of their levels. The effects of progestins depend on the cell phenotype, including the composition and proportion of different receptors, activity of signaling pathways, and expression of transcription factor coregulators and steroid metabolism enzymes. The role paracrine regulation plays in the progestin effect is described. Particular attention is paid to the progestin effect on the tissues where progestins are thought or known to affect carcinogenesis or to stimulate or suppress the tumor growth, that is, to modulate cell proliferation, apoptosis, and the epithelial-mesenchymal transition.

The state of the viscosity of erythrocyte membranes in breast cancer patients (68--in menopause and 32--with menstrual cycle) was studied in comparison with the content of steroid hormone receptors in the tumor tissue and the age of patients. It is showed that the less hormone dependence of the tumor the higher viscosity of erythrocyte membranes that manifested by a decrease in the coefficient of eximerization (CE) of pyrene in the protein/lipid and in particular, lipid/lipid membrane layers. Increasing CE of pyrene in lipid/lipid layer of erythrocyte membranes above 1.7 units, reflecting a decline in their microviscosity, could be considered as an additional extra-tumor criterion for identification of the tumor as of hormone dependent type.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are unusual and rare epithelial tumors for which the diagnosis of the grade of malignancy and prognostic assessment on the basis ofhistology represent considerable challenges for the pathologist. In this study we conducted a retrospective analysis of the cell proliferation (Ki-67 nuclear antigen) in primary and metastatic GEP NENs of 137 patients as well as the assessment of keratin 19 (CKI9) and progesterone receptors (PR) expression in pancreatic NENs of 57 patients. In 19 (27,1%) GEP NEN metastases was found I,5-4,5-fold increase of Ki-67 index compared with their primaries. Consequently, 6 (21,4%) cases of NETGI and 4 (7,0%) cases of NET G2 were up-graded Pancreatic NETs G2 with Ki-67 index >5% were significantly associated with presence of distant metastases (p =0,007) and decreased survival (p=0,03). Decreased survival also was found in the group of gastrointestinal NET G2 with Ki-67 index > 15% (p=0,005). Further analysis of immunomorphological features and proliferative activity allowed to separate a rare group of tumors - ("NET G3", characterized by decreased survival comparing to NET G2. Expression of CKI9 in pancreatic NETs was significantly associated with higher proliferative activity of primary tumor (p =0,04) and adverse outcome (p=0,003). On other hand, PR expression correlated with lower Ki-67 index (p=0,006), absence of metastases (p=0,004) and favorable outcome (p=0,000). Our results show that Ki67 index is a key parameter of morphological diagnosis of GEP NENs. Thus, the studied markers are important parameters of the morphological diagnostic of GEP NENs, which allow more accurately assess the degree of malignancy, prognosis and treatment of the disease.

It has been shown that specific binding of dydrogesterone with progesterone receptors in blood mononuclear cells of the patients included in the programs of in vitro fertilization, varies from 0 to 298%, thus at 38% of women dydrogesterone concedes to a progesterone in the competition for receptors of a progesterone, and 62%--exceed. The revealed variations of specific binding dydrogesterone with receptors of a progesterone are a reserve of increase of efficiency of auxiliary reproductive technology at the expense of individual selection of hormonal agents.

Numerical densities of the nuclei were morhometrically evaluated in all myocytes and myocytes expressing nuclear estrogen- and progesterone-receptor complexes, which were revealed immunohistochemically with monoclonal antibodies in C57Bl/6 mice. It was shown that the above quantitative parameters of myometrial cells after the first pregnancy were similar to those in nonpregnant mice by day 10 after delivery. In the third pregnancy, especially developed after the second interrupted pregnancy, proliferation processes in the myometrium were not completed by postpartum day 10, but dramatically progressed. It was associated with a significant decrease in the fraction of myocytes carrying nuclear hormone-receptor complexes with estradiol and progesterone and their disturbed physiological relations in the myometrium during and after pregnancy probably due to dedifferentiation of a considerable part of myocytes.

Although there is data suggesting the in vitro inhibition of aromatase in cell lines by antidiabetic biguanide metformin (MF), there is no data on the intratumoral breast cancer (BC) aromatase expression in patients already receiving therapy for type II diabetes. Paraffinized tumor samples obtained from 57 BC pts aged 48-77 yrs, >80% of pts had stage T1-2N0-3M0 BC. Thirteen of the pts didn't have diabetes, 44 pts were previously diagnosed type II diabetes and reseaved the following therapy for at least 1 year: diet only (n=14), sulphonylurea (SU, n=14), metformin (MF, n=9) or MF with SU (n=7). Tumor samples were deparaffinized in xylene and treated with the monoclonal aromatase antibody 677. The rate and intensity of tissue staining was then analyzed by semi-quantitative method using conventional scores. Negative controls were processed with 0.01 M PBS instead of the specific antibody. For positive control paraffin-embedded human placenta samples were used. By conventional scores method the following values were obtained: 1.31 (pts without diabetes), 1.47 (all diabetic patients), 2.22 (MF), 1.50 (SU), 1.29 (MF+SU), 1.81 (MF and MF+SU), 1.07 (diet). Allred scores for progesterone receptor (PR) were the highest in the samples from pts treated with MF or MF+SU and the lowest in the samples obtained from SU-treated pts. Thus, in contrast to previous findings suggesting the suppressive effect of MF on aromatase in vitro, no such trend was discovered for aromatase expression in tumor samples from diabetic patients treated with MF. Although the investigated patients population is still small, this data combined with clinical data (higher PR levels) may suggest the better responses to hormonal therapy in MF-treated diabetic patients.

The authors present the data available in the literature and the results of their studies of intraoperative specimens from 24 patients with mucinous cystic tumors of the pancreas. The latter are a special group of neoplasms that are unrelated to the gland's ducts and consist of the mucin-producing epithelium with underlying ovarian-like stroma. Mucinous cystadenocarcinoma are detectable in older women (mean age 54.8 years), they are large and multicompartmental in nature. Microscopic study has indicated that all types of mucinous cystic tumors are characterized by ovarian-like stroma, the cells of which show a positive reaction to progesterone receptor antibodies. More significant ovarian-like stroma is typical of mucinous cystadenoma. The high (more than 30%) proliferative activity of epithelial lining cells is suggestive of the malignant nature of the process.

Modern data on molecular mechanisms underlying intracerebral pleutropic action ofgestagens (progesterone, its metabolites, and synthetic gestagens) are reviewed. Properties of classical and membrane-bound progesterone receptors involved in regulation of gene expression, modulation of neurotransmitter systems, and activation of signal cascades in neurons are described along with data of regional distribution of progesterone receptor subtypes in brain, metabolism, functional activity, and mechanisms of action of progesterone metabolites. Special attention is given to analysis of progesterone and metabolite neuroprotective activity in CNS, such as anti-inflammatory and antiapoptotic effects, and participation in neurogenesis regulation. Clinical application of progesterone-based drugs is discussed with reference to the treatment of brain injuries and prospects for extension of indications for their use in neurologic practice.

In this study cytostatic and chemosensitizing actions of gestagens are described. Cytostatic mechanisms can be divided into estrogen-mediated and independent ones. The former include down-regulation of estrogen receptors, induction of 17?-hydroxysteroid dehydrogenase and estron sulfotransferase. The latter are MAP-kinase inhibition, induction of cell differentiation and apoptosis. Chemosensitization by gestagens is due to inhibition of P-glycoprotein, GST and MRP. Another putative chemosensitization mechanisms involves mitochondrial transition pore (MTP), at least for such gestagens as buterol and acetomepregenol. Elucidation of common mechanisms of MTP and MDR regulation and the possible role of MTP in chemosensitization is a new direction of investigations into the action of steroid hormones.

The immunohistochemical technique was used to study the levels progesterone and estrogen-alpha receptors in the smooth muscle cells, by examining the specimens taken from 168 leiomyosarcomas (LMS) and 106 leiomyomas (LM) of the corpus uteri. The presence and degree of receptor expression were shown to be related to the proliferative activity (PA) (Ki67 protein expression), the activity of argyrophilic proteins in the nucleolar organizer region (Ag-NOR-protein) (silver-plating with AgNO3, as described by Y. Daskal) and the proteins regulating the apoptotic system (Bcl-2 expression) (93.4 +/- 1.1%). The presence of sex hormone receptors in LMS was associated with low PA (8.5 +/- 3.3%), the decreased synthesis of Ag-NOR proteins (15.1 +/- 2.7%), and high Bcl-2 activity (93.4 +/- 1.1%) although the presence of the receptors had no significant effect on p53. The negative expression of both types of receptors was characteristic for LMS and associated with high PA (19.3 +/- 3.1%), the high expression of Ag-NOR-proteins (25.3 +/- 2.6%), and a drastic reduction in the amplification of Bcl-2 (38.4 +/- 10%) in reference to the positive receptor status. Receptor coexpression was associated with relatively low PA, the expression of argyrophilic proteins and the relatively high expression Bcl-2 without any noticeable impact on the expression of p53.

Published data on in vitro stimulation of oocyte maturation and ovulation by gonadotropic and steroid hormones in different teleost species are reviewed. The involvement of meiosis-inducing steroids, eicosanoids, and nuclear progesterone receptor in the mechanism of ovulation induction is considered.

Rapid, independent of transcriptional effects of progesterone have been observed in various types of cells, tissues and species. In some biological systems, these nongenomic actions and associated with them signal transduction pathways are characterized in detail at molecular level. This review summarizes findings concerning the role of progestins in the regulation of such physiological functions and processes as meiotic maturation of fish and amphibian oocytes; growth and proliferation of normal and transformed cells of mammary gland; contraction of myometrium; survival and functional activity of granulose cells; sperm capacitation, acrosome reaction and hypermotility; immune function of T lymphocytes; survival and function of brain cells. The participation of several types of receptor proteins in the nongenomic progesterone signaling is discussed. They include the classic nuclear progesterone receptor, PR, the membrane progestin receptor, mPR, the progesterone membrane receptor component, PGMRC, the oxytocin receptor, OTR, and the GABA receptor, GABA(A).

Clinical and experimental effects of neoadjuvant treatment of endometrial cancer patients with non-steroidal aromatase inhibitors: letrozole (femara, n=10, 2.5 mg/day, 14 days), anastrozole (arimidex, n=15,1 mg/day, 28 days) and exemestane (aromazine, n=13, 25 mg/day, 14 days) were compared. Administration of anastrozole was mostly frequently followed by pain relief in the lower abdomen and/or decreased rates of uterine discharge. Endometrial wall thickness (M-echo signal) decreased significantly in 60% of patients receiving anastrozole, exemestane - 58.3% and letrozole - 40%. Substantial drop in intratumoral aromatase and blood estradiol levels occurred more frequently after anastrozole and letrozole while progesterone receptor levels in tumor were markedly lower after exemestane administration. Assay of blood LH (except letrozole), FSH and cholesterol appeared to be of less relevance. On the contrary, significance of assessment of marker Ki-67 expression, which, in the case of anastrozole, dropped in 6 out of 12 patients after a 28-day course, could hardly be underestimated.

Endometrial scrapes and biopsy specimens from 47 females with primary and secondary infertility were studied by histological and immnohistological (estrogen and progesterone receptors, Ki67) methods. Endometrial abnormalities, such as luteal phase defect, hyperplasia, endometrial polyps, and chronic endometritis, were detected in all the patients. There were considerable changes in the expression of estrogen and progesterone receptors and impaired endometrial proliferative processes. There was no clear correlation of immunohistochemical parameters with blood hormone levels in both primary and secondary infertility. The findings may be of significance in choosing the schemes of assisted procreation technologies.

The effects of 100 mg/kg mifepristone administration from 1 to 5 postnatal days on formation of the female reproduction functions were studied. It has been shown that neonatal blockade of progesterone receptors resulted in significant decline of morphometric parameters of the adult rat uterus, as well as disturbance sex steroids secretion and decrease density of uterus progesterone receptors in the oestrus. Neonatal administration of mifepristone did not change the rat ability to reproduction in favorable condition, but induced significant fetus resorption under the gestation pathology. These data suggest that violation of progesterone receptors mechanisms in neonatal period of life exert negative influence on the female reproduction functions in adult. We suggest, that neonatal treatment of mifepristone can been used as a model of progesterone receptors deficit in the adult rat uterus.

Prognostic significance of sex hormones, sex hormone-binding globulin, estrogen and progesterone receptors as well as the activity of enzymes involved in estrogen synthesis (aromatase, steroid sulfatase, estrogen hydroxylase, catechol-O-methyl transferase, glutathione-S-transferase) were investigated in 74 endometrial carcinoma patients. Stage and duration of uterine myoma history appeared to be significant factors of overall survival. Such factors as stage, depth of myometrial invasion, body mass, blood-serum estradiol level as well as aromatase and catechol-O-methyl transferase concentration in tumor tissue were significant for free-relapse free survival period.

Chemical modification of progesterone molecule leads to changes both in the gestagenic activity of new derivatives and in their specific binding with progesterone receptors. The passage from esters (acetomepregenole, butagest) to the corresponding OH-forms such as 17a-acetoxy-3b-hydroxy-6-methyl-pregna-4,6-dien-20-one (ABMP)is accompanied by an increase in the binding with progesterone receptors in vitro. The translocation of a double bond from endocyclic (N6-N7) to exocyclic position (methylene group at N6 in ABMP) has no significant effect on the ability to binding with progesterone receptors.

Proliferation and the state of adhesion molecules (E-cadherin, galectin-3) and estrogen and progesterone receptors were immunohistochemically analyzed in breast cancer biopsy specimens under conditions of c-erbB2 overexpression with and without gene amplification. It was hypothesized that c-erbB2 overexpression without gene amplification led to suppression of proliferation and "conservation" of tumor cell.

The analysis of the histopathologic features in 138 patients with uterine serous adenocarcinoma in comparison with 146 patients with uterine endometrioid papillary adenocarcinoma revealed morphological specificities of these carcinomas. Immunohistochemical study found that 66.7% uterine serous adenocarcinomas were negative both to estrogen and progesterone receptors and 86.7% uterine serous adenocarcinomas showed p53 oncoprotein overexpression. The data support the hypothesis that uterine serous adenocarcinoma is a hormone-negative tumor and that mutation of p53 tumor suppressor gene may play a leading role in its carcinogenesis.

Immunohistochemical investigations were performed in 22 cases of breast cancer. The objective of this study was to assess the presence and distribution of ER and PR in the cancer tissue. We found that expression of the ER and PR in the cancer tissue is variable, which depends on cancer histogenesis (lobular, ductal), histological form, differentiation grade, and stage of its development. Level of the expression of ER and PR was higher in the ductal form than in the lobular form of breast cancer. Expression of the ER was significantly higher than expression of PR in the case of the lobular form. There were no similar differences seen in cases of ductal form of breast cancer.

The clinical and endocrine-related effects of 2-week preoperative treatment of endometrial carcinoma patients with a non-steroid inhibitor of letrozole aromatase (femara 2.5 mg/day, n=10) and a steroid inactivator of the enzyme (exemestane 25 mg/day, n=13) were compared. In the first group, pain relief in the lower part of the belly and/or decreased uterine discharge were reported in two cases, as well as a 31% drop in the mean endometrial M-echo (ultrasound) signal. In the exemestane group, two patients revealed moderate uterine discharge decrease matched by a 15.6% decrease in M-signal intensity; no tumor was detected in another patient on completion of the course. Letrozole effect was relatively greater when such parameters as tumor-tissue aromatase level, estrogen concentration in vaginal smear and blood-cholesterol, FSH and LH levels were taken into consideration. However, exemestane therapy involved a relatively sharper drop in the levels of tumor receptors of progesterone and a significantly higher estrogen/progesterone receptor ratio. Hence, no matter how short treatment duration was, both steroid and non-steroid aromatase inhibitors induced effects predominantly associated with lowering estrogen production in endometrial carcinoma patients. This makes a case for further clinical trials of these drugs to deal with the pathology.

This work is devoted to the vital topic of the influence of partial androgen deficiency of aging men (PADAM) on the development of cells with androgen receptors. The results obtained in this study suggest a conclusion that the production of testosterone by some tumors and tissues of the peritumorous zone, which is accompanied by increased proliferative activity and disturbance of the regulation of the cell cycle, is caused by PADAM. The given changes are directed at compensating for testicular deficiency (in particular at overcoming the androgen-dependent stage of development of androgen-sensitive cells). These changes are a partial manifestation of metabolic syndrome (X-syndrome). The atypical cells, which unavoidably develop during metabolic syndrome, are dealt with by means of the immune system, whose capabilities become less and less adequate in the given circumstances.

Competition of a number of progesterone 16alpha,17alpha-cycloalkane derivatives with 3H-labeled ligands for the binding sites of the rat uterine progesterone receptor, uterine pentaranophilin, and blood serum pentaranophilin was studied. We found that the selective ligands for the progesterone receptor are progesterone, 16alpha,17alpha-cyclopropanoprogesterone, and 16alpha,17alpha-cyclopent-3'-enoprogesterone and the selective ligands for serum pentaranophilin are 6alpha-methyl-16alpha,17alpha-cyclohexanopregna-1,4-diene-3,20-dione and 3beta-hydroxy-16alpha,17alpha-cyclohexanopregn-5-en-20-one. No selective ligands for the uterine pentaranophilin were found. The majority of substituents in rings A, B, and D' we studied decreased the affinity of ligands for all the three proteins. The substitution of the delta5-3beta-hydroxy grouping for the delta4-3-keto grouping exerted the strongest negative effect in the case of the progesterone receptor and the uterine pentaranophilin, whereas the introduction of the 3',4'-dimethyl grouping strongly inhibited the ligand affinity for the uterine pentaranophilin. The extent and even the direction of the effect of a substituent on the affinity of ligands for the proteins substantially depended on the presence of other substituents in the steroid molecules. We hypothesized that a certain similarity exists between three proteins studied in respect to the structures of their ligand-binding pockets. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

We examined 39 women with normal endometrium and 139 women with glandular-cystic hyperplasia of the endometrium (without atypia). According to clinical manifestations of hyperplasia, the patients were divided into 3 groups: 74 (53%) had reestablishing menstrual function after total curettage (group 1); 42 patients (30%) with glandular-cystic hyperplasia after curettage and hormonal therapy with progesterone and synthetic progestins (duration 3 to 6 months) had no repeated pathology of the endometrium (group 2); endometrial hyperplasia recurred 2 and 3 times as showed biopsies during 2-5 years of observation in 23 (17%) women (group 3). Immunohistochemical tests of normal endometrium revealed correlations between stages of menstrual cycle and steroid hormone receptors in nuclei of glandular epithelium and stromal cells. Maximum sensitivity of glandular epithelium to estrogen and pronounced expression of estrogenic receptors were observed at middle and late stages of proliferation. High sensitivity of glandular epithelium to progesterone was registered at middle and late stages of proliferation and early stage of secretion. Two types of hormone receptor expression were observed. Type 1 typical for the endometrium of middle and late stage of proliferation was characterised by a high content of receptors to E2 and P in glandular epithelium and stromal cells. Type 2 was observed in patients with recurring glandular hyperplasia and was characterised by a mosaic picture up to complete absence of receptor expression in nuclei of some glands and stromal cells. The detected zones free of receptors to estrogens and progesterone evidence for local disturbance of a regulating role of signal pathways of sexual steroids and can serve a substrate for formation of tissue autonomy.

Estrogen (ER) and progesterone (PR) receptors were assayed immunohistochemically in cytological smears and histological samples from 30 breast cancer patients. Since the results reported by the two research centers matched by 73%, it is suggested that running ER and PR determinations on cytological smears in cases of inoperable cancer, preoperative therapy and monitoring may be recommended. Therefore, the 3-4 year old records on ER and PR determinations should be regarded as null and void.

The contents of receptors of steroid hormones (estrogen and progesterone) in cerebral meningioma was studied up. Comparison between this hormones level and mostly significant clinico-morphological characteristics of meningioma was conducted. High frequency of estrogen and progesterone revealing in the tumor tissue permits to suggest the possibility of their application as a test of her hormonal sensitivity and is important for the disease course prognosis and an adequate methods of treatment choice as well.

The binding of [3H]progesterone and [3H] 16 alpha,17 alpha-cycloalkanoprogesterones to proteins from rat, rabbit, and human uteri and other organs was studied. We found that 16 alpha,17 alpha-cycloalkanoprogesterone derivatives display affinities for the uterine progesterone receptors comparable with that of the natural hormone and no substantial species differences in the affinity. Rabbit uterus was found to have no proteins distinct from the progesterone receptor that specifically bind [3H] 16 alpha,17 alpha-cycloalkanoprogesterones. At the same time, in the human uterus, we found another protein that binds some of these progesterone derivatives; it turned out to be similar to the protein from rat uterus. A similar protein with the same selectivity and affinity for steroids was also found in rat and human kidneys. Blood serum, liver, lung, and a number of other tissues were found to contain a protein of the third type that binds the same 16 alpha,17 alpha-cycloalkanoprogesterones and exhibits submicromolar Kd values for these steroids and a very low affinity for progesterone. We speculated that the introduction of a bulky substituent adjacently to the 17 beta-side chain of progesterone could result in a change in the general biodynamics of the derivative including its transport, uptake, and accumulation in tissues, which may determine the selectivity of its effect.

A comprehensive clinical, histological, and immunohistochemical evaluation was done of 42 intracranial meningiomas in patients with hyperostosis in the postoperative period. It has been ascertained that hyperostosis in meningiomas is a direct bone tumour invasion. Bone invasion is not a sign of malignant transformation of meningiomas. It is shown that meningiomas with hyperostosis are hormone-dependent tumours. In tumours, there has been detected a high concentration of progesterone and estrogen active receptors. It is shown that hyperostosis is a consequence of hormone-related abnormalities of Ca metabolism. Special stress is laid on ridding the bone of hyperostosis at tumour removal to reduce the number of tumour recurrences.

Level of sex steroid hormones being changed throughout an estrous cycle influences physiological and behavioral features of female subjects. To test how estrogen and progesterone affect the anxiety level in mice the ovariectomy (OVX) followed by hormone treatment was carried out. After 1 week of recovery period estradiol benzonate (20 micrograms, s/c) was injected once a day during 7 consequent days. By the 7th day in addition to EB injection progesterone (500 micrograms, s/c) was also injected. Four hours later the mice were tested in elevated plus-maze to measure the anxiety level. Control animals were treated with sesame oil only. Behavioral data obtained demonstrate that the hormonal treatment altered anxiety state in experimental animals. In plusmaze paradigm, it has been demonstrated that progesterone-treated mice revealed the lowest level of open arm activity. In contrast, these mice showed the highest grooming activity as compared to other experimental groups. Immunohistochemical data on progesterone receptor (PR), immunoreactivity in brain have shown that the manipulation with different hormonal treatments modified the number of PR-ir cells in many brain areas. Our data suggest that sex steroid hormones play an important role in induction of anxiety level, as measured by elevated plus-maze, and this action might be partially mediated through the classical steroid receptors.

In examining 502 female patients with cancer of the ovaries (OC) infertility was identified in 21.9 percent of cases. The prevalent form of infertility was tubal infertility (92.7%), there were but a few instances of the endocrine form (1.8%). The infertile women were studied for their hormonal and receptorial status (receptors of estradiol and progesterone). It has been established that women with the endocrine variant of infertility present with more prominent hormonal inadequacies in the hypophysis-ovaries system and manifest changes in the receptorial status of the ovaries than those with tubal infertility; the findings in the latter have not been shown to be different from controls. In endocrine infertility OC is in fact not encountered, which fact can be related to morphological features of the ovaries giving origin to endocrine disturbances, and to a decline in the receptorial status and absence of ovulation.

The effects of neoadjuvant therapy with neovir, provera and their combinations on endometrial tumor morphology, progesterone (PR) and estradiol (ER) receptor levels were studied in 50 patients, aged 40-78, with primary tumors stage I-III, and without concomitant pathology. A 19-day course of neovir did not alter tumor morphological status but was followed by a significant rise in PR and ER concentrations. After neoadjuvant therapy in combination with provera, which generally lowers cytoplasmic receptor levels, mean values of receptors dropped in PR+ tumors while, in PR- tumors, they increased significantly. Our findings suggest that neovir may be used in clinic to stimulate endometrial tumor sensitivity to specific hormonal therapy, particularly, for hormone-independent neoplasia.