Estrogen and Progesterone Receptor Immunoexpression in Fallopian Tubes among Postmenopausal Women Based on Time since the Last Menstrual Period.

Existing data on the expression of estrogen receptor (ERα) and progesterone receptor (PR) in fallopian tubes in postmenopausal women are mostly inconclusive. Therefore, we assessed ERα and PR immunoexpression in the oviducts of these women. One hundred postmenopausal women were divided into three groups based on time elapsed since the last menstrual period: (A) 1-5 years, (B) 6-10 years, and (C) ≥11 years. In all groups, both in the glandular epithelium and stroma of the ampulla and isthmus of the oviduct, immunolocalization of ERα and PR were noted. The glandular epithelium of the ampulla showed a higher percentage of PR-positive cells than the isthmus in each group. Regarding ERα, there were no significant differences. In the glandular epithelium in both the ampulla and isthmus, the percentage of ERα- and PR-positive cells was significantly higher than that in the stroma in each study group and higher in the A group than in the C group. In conclusion, in postmenopausal women, time elapsed since the last menstrual period in the fallopian tubes was positively correlated with the following: (1) the epithelium showed vacuolation of cytoplasm with greater frequency, (2) the proportion of ciliated cells decreased, and (3) the percentage of ERα- and PR-positive cells also decreased. The obtained results indicate a significant decrease in ERα and PR expression depending on the time that has elapsed since the last menstruation, which is undoubtedly related to the loss of the reproductive function of the patients.

Markers of Inflammation and Vascular Parameters in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids.

The exact mechanism of selective progesterone receptor modulator action in leiomyoma still challenges researchers. The aim of the study was to assess the effects of ulipristal acetate (UPA) on immunoexpression of inflammatory markers and vascularization in fibroids. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction), (3) and no response to treatment (no decrease or increase in fibroid volume). The percentage of TGFß, IL6, IL10, CD117, and CD68-positive cells were significantly lower in the group with a good response to treatment vs. the control group. Moreover, the percentage of IL10 and CD68-positive cells in the group with a good response to treatment were also significantly lower compared to the no response group. Additionally, a significant decrease in the percentage of IL10-positive cells was found in the good response group vs. the weak response group. There were no statistical differences in the percentage of TNFα-positive cells and vessel parameters between all compared groups. The results of the study indicate that a good response to UPA treatment may be associated with a decrease of inflammatory markers, but it does not influence myoma vascularization.

Alterations in fecal short chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) in men with benign prostatic hyperplasia (BPH) and metabolic syndrome (MetS).

Gut microbiome-derived short-chain fatty acids (SCFAs) emerge in the process of fermentation of polysaccharides that resist digestion (dietary fiber, resistant starch). SCFAs have a very high immunomodulatory potential and ensure local homeostasis of the intestinal epithelium, which helps maintain the intestinal barrier. We analyzed the association between stool SCFAs levels acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0i), butyric acid (C 4:0n), isovaleric acid (C 5:0i) valeric acid (C 5:0n), isocaproic acid (C 6:0i), and caproic acid (C 6:0n)) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 183 men (with BPH, n = 103; healthy controls, n = 80). We assessed the content of SCFAs in the stool samples of the study participants using gas chromatography. The levels of branched SCFAs (branched-chain fatty acids, BCFAs): isobutyric acid (C4:0i) (p = 0.008) and isovaleric acid (C5:0i) (p < 0.001) were significantly higher in patients with BPH than in the control group. In healthy participants isocaproic acid (C6:0i) predominated (p = 0.038). We also analyzed the relationship between stool SCFA levels and serum diagnostic parameters for MetS. We noticed a relationship between C3:0 and serum lipid parameters (mainly triglycerides) in both healthy individuals and patients with BPH with regard to MetS. Moreover we noticed relationship between C4:0i, C5:0i and C6:0i and MetS in both groups. Our research results suggest that metabolites of the intestinal microflora (SCFAs) may indicate the proper function of the intestines in aging men, and increased BCFAs levels are associated with the presence of BPH.

Markers of Cellular Proliferation, Apoptosis, Estrogen/Progesterone Receptor Expression and Fibrosis in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids.

There appear to be very few data on the exact mechanisms of a selective progesterone receptor modulator action in myomas. The aim of the study was to assess the effects of ulipristal acetate (UPA) on fibroids, especially on estrogen receptor (ER) and progesterone receptor (PR) immunoexpression, proliferation, apoptosis and tissue fibrosis, and to compare the above parameters in untreated (surgical attention only) and UPA-treated leiomyomas. UPA-treated patients were divided into three groups: (1) good response (≥25% reduction in volume of fibroid), (2) weak response (insignificant volume reduction) and (3) no response to treatment (no decrease or increase in fibroid volume). The study observed a significant decrease in the percentage of collagen volume fraction and ER and PR immunoexpression in the good response group, in the percentage of proliferating cell nuclear antigen (PCNA)- and Ki67-positive cells in the groups with good and weak reactions vs. control group; significantly higher apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells) in the good reaction group vs. control group. The results of the study indicate that a good response to UPA, manifested by a volume reduction of myoma, may be associated with a decrease in fibrosis, ER/PR and PCNA and Ki67 immunoexpression and an increase in cell apoptosis within the myoma.

The Effects of Long-Term Immunosuppressive Therapies on the Structure of the Rat Prostate.

Background: Little is known about the overall impact of immunosuppressive drugs on the prostate. The study aimed to determine the impact of different protocols of immunosuppressive treatment on the structure of the rat ventral prostate. Methods: For 6 months, 48 male Wistar rats received immunosuppressive drugs: cyclosporin A, tacrolimus, mycophenolate mofetil, rapamycin, and prednisone, according to three-drug protocols. Light and transmission electron microscopic studies, and quantitative evaluation of immunohistochemical expression of selected intermediate filaments, CD117+ mast cells, and CD138+ plasma cells were performed in the rat ventral prostate. Results: In all experimental groups, acini focal hyperplasia, changes to the ultrastructure of the glandular epithelium, changes in the expression of cytokeratins and desmin, and numerous mast and plasma cells in the prostate stroma were found. In cyclosporine-A-based groups, atrophy and numerous intracellular vacuoles were observed. In groups where a three-drug treatment was replaced with rapamycin, morphological alterations were less severe compared to those without conversion. Conclusions: In the rat ventral prostate, (1) immunosuppressive protocols affect the morphology and immunohistochemical expression of intermediate filaments, (2) morphological alterations, expression, and localization of selected proteins are not connected with adenocarcinoma development, and (3) conversion of the treatment to rapamycin may prevent hyperplastic abnormalities.

The Relationship between Eicosanoid Levels and Serum Levels of Metabolic and Hormonal Parameters Depending on the Presence of Metabolic Syndrome in Patients with Benign Prostatic Hyperplasia.

Background: The purpose of our investigation was to analyze the relationship between the serum levels of inflammatory mediators (HETE, HODE) and the levels of selected metabolic and hormonal parameters in patients with benign prostatic hyperplasia (BPH) with regard to concomitant metabolic syndrome (MetS). Methods: The study involved 151 men with BPH. Blood samples were taken for laboratory analysis of the serum levels of metabolic and hormonal parameters. Gas chromatography was performed using an Agilent Technologies 7890A GC System. Results: We found that waist circumference was the only parameter related to the levels of fatty acids, namely: 13(S)-HODE, 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE. In the patients with BPH and MetS, triglycerides correlated with 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE, which was not observed in the patients without MetS. Similarly, total cholesterol correlated with 9(S)-HODE, and 15(S)-HETE in the patients with BPH and MetS, but not in those without MetS. In the group of BPH patients with MetS, total testosterone positively correlated with 13(S)-HODE, and free testosterone with 9(S)-HODE. Conclusions: Based on this study, it can be concluded that lipid mediators of inflammation can influence the levels of biochemical and hormonal parameters, depending on the presence of MetS in BPH patients.

Comparison between selected hormone and protein levels in serum and prostate tissue homogenates in men with benign prostatic hyperplasia and metabolic disorders.

PURPOSE: The purpose of the study was to assess the relationship between changes in the levels of selected hormones in serum and prostate tissue homogenate in regard to metabolic disorders in patients with diagnosed, surgically treated benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study involved a group of 154 men with a diagnosis of BPH with metabolic syndrome (MetS) and without MetS. The serum levels of the hormones - total testosterone, free testosterone, insulin, dehydroepiandrosterone sulfate, estradiol, luteinizing hormone, sex hormone binding globulin (SHBG), and insulin-like growth factor-1 (IGF-1) - were determined using the ELISA method. Prostate tissue sections obtained from the patients during transurethral resection of the prostate were frozen in liquid nitrogen. We determined the levels of the same hormones. RESULTS: There was a statistically significant difference between the groups in terms of serum SHBG levels, but not in the prostate tissue SHBG levels. A similar relationship was observed in regard to IGF-1, the serum levels of which were significantly higher in patients with MetS. MetS had an effect on the ratio of hormone levels in serum to their levels in the prostate tissue. Correlations between the levels of biochemical parameters and the levels of hormones in serum and the prostate tissue of BPH patients with and without MetS demonstrate that serum SHBG levels correlated weakly with waist size and triglyceride levels. CONCLUSION: The occurrence of MetS in BPH patients was associated with changes in the levels of hormones and proteins. These changes, however, were not always equivalent to changes in the levels of these parameters in prostate tissue. It should also be mentioned that MetS in BPH patients had an influence on a quantitative balance between the levels of SHBG in serum and prostate tissue.

Apoptosis and proliferation of the prostate cells in men with benign prostatic hyperplasia and concomitant metabolic disorders.

INTRODUCTION: Apoptosis and proliferation of prostate cells are associated with both physiological increase and hyperplasia of the prostate. The aim of this study was to determine the contribution of metabolic syndrome to the processes of apoptosis and proliferation in gland epithelial cells and prostatic stromal cells in men with BPH. SUBJECTS AND METHODS: The study involved 151 men, aged 52-89 years, receiving pharmacological treatment for BPH. The men were divided into two groups: those with and those without metabolic syndrome. The serum levels of the parameters were determined. Reactions for the identification of apoptosis (TUNEL) and proliferation (PCNA) in cells were also performed. RESULTS: The relationships between the number of TUNEL(+) and PCNA(+) cells and metabolic syndrome were not observed. It was found that the total number of TUNEL(+) cells in the prostate stroma correlated negatively with the levels of high-density lipoprotein and insulin-like growth factor-1. The analysis of the correlations in BPH patients with and without metabolic syndrome demonstrated that the only parameter correlating with the number of PCNA(+) cells in the prostate stroma was insulin resistance. CONCLUSION: Metabolic syndrome in patients with BPH had no impact on the number of TUNEL(+) and PCNA(+) cells in the prostate gland. However, the disturbed levels of metabolic parameters, and deviations of anthropometric parameters from normal may influence the number of apoptotic and proliferating cells.

Molecular Analysis of the SRD5A1 and SRD5A2 Genes in Patients with Benign Prostatic Hyperplasia with Regard to Metabolic Parameters and Selected Hormone Levels.

Introduction: The etiology of benign prostatic hyperplasia (BPH) has not so far been fully explicated. However, it is assumed that changes in the levels of hormones associated with aging can contribute to the development of prostatic hyperplasia. Dihydrotestosterone combines with the androgen receptor (AR) proteins of the prostate gland. Enzyme activity is based on two isoenzymes: type 1 and type 2. 5α-reductase type 1 is encoded by the SRD5A1 gene, and type 2 is encoded by the SRD5A2 gene. The aim of our study was to determine the frequency of the SRD5A1 (rs6884552, rs3797177) and SRD5A2 (rs523349, rs12470143) genes' polymorphisms, and to assess the relationships between the genotypes of the tested mutations, and the levels of biochemical and hormonal parameters in patients with BPH. Material and Methods: The study involved 299 men with benign prostatic hyperplasia. We determined the serum levels of particular biochemical parameters-fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG)-by the spectrophotometric method, using ready reagent kits. The ELISA method was used to determine the levels of the following hormonal parameters and proteins: total testosterone (TT), free testosterone (FT), insulin (I), luteinizing hormone (LH), and sex hormone binding protein (SHBG). Metabolic syndrome was diagnosed. Genotyping was performed by real-time PCR. Results: We analyzed the relationships between the incidence of particular diseases and the genotypes of the SRD5A1 and SRD5A2 polymorphisms among patients with BPH. The BPH patients with the CC genotype of the SRD5A2 rs523349 and rs12470143 polymorphisms were considerably less frequently diagnosed with metabolic syndrome (MetS) (p = 0.022 and p = 0.023 respectively). Our analysis revealed that homozygotes with the CC of the SDR5A2 rs12470143 polymorphism had visibly higher HDL levels than those with the TT and CT genotypes (p = 0.001). Additionally, we found that the patients with the CC genotype of the SDR5A2 rs12470143 polymorphism had considerably higher FT levels (p = 0.001) than the heterozygotes with the CT and the homozygotes with the TT of the genetic variant analyzed in our study. Furthermore, the patients with at least one G allele of the SRD5A2 rs523349 polymorphism had significantly lower SGBG levels (p = 0.022) compared with the homozygotes with the CC genotype. The presence of at least one A allele (AA + AG genotypes) of the SRD5A1 rs3797177 polymorphism entailed notably lower serum insulin levels than those observed in homozygotes with the GG genotype (p = 0.033). Conclusions: The study described in this article shows that selected SRD5A1 and SRD5A2 polymorphisms can alter the levels of metabolic and hormonal parameters in patients with BPH. Special attention should be paid to the SDR5A2 rs12470143 polymorphism, which is associated with a change in lipid profile, as well as with the inheritance and incidence rate of MetS among these patients. An analysis of the frequency of this polymorphism among BPH patients could be useful in estimating the risk of getting ill, and planning therapies of concomitant diseases for BPH patients.

Effects of an immunosuppressive treatment on the rat prostate.

The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three-drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins.

The influence of immunosuppressants on the morphology, proliferating cell nuclear antigen (PCNA) and apoptosis in the rat ventral prostate.

AIM: Analysis of the impact of immunosuppressants on apoptosis and PCNA in the rat ventral prostate. METHOD: The studies were performed on 48 male Wistar rats. The animals were divided into a control group and 7 experimental groups. For 6 months, the rats were administered drugs such as: rapamycin (Rapa), cyclosporin A (CsA), tacrolimus (Tac), mycophenolate mofetil (MMF) and glucocorticosteroids (GS). During section of the rats, prostate ventral lobes were obtained. Morphological evaluation (HE, PAS), TUNEL assay, PCNA expression analysis and quantitative image computer analysis were performed. RESULTS: The highest percentage of apoptosis in epithelial cells was observed in groups which received two combinations of drugs: (V) CsA, MMF, GS and (VII) Tac, MMF, GS. A much lower percentage of apoptotic epithelial cells was found in the groups where the treatment schemes included rapamycin throughout the duration of the study. Interestingly, the conversion of the treatment to rapamycin caused a significant reduction of apoptosis in epithelial cells as well as in proliferation in both epithelial and stromal cells. CONCLUSIONS: On one hand, the obtained results may explain the anticancer activity of rapamycin in reducing the proliferation of epithelial cells, and on the other hand the adverse effect of rapamycin in the form of reduced regeneration of these cells. Taking into account the prostate in isolation from other organs/systems, the dosage scheme with Rapa, Tac and GS would appear to be the most favorable, due to the smallest morphological changes.

Morphological and immunohistochemical comparison of three rat prostate lobes (lateral, dorsal and ventral) in experimental hyperprolactinemia.

UNLABELLED: The prolactin plays an important role in the regulation of growth and differentiation of prostate gland besides androgens. The goal of this study was to reveal the influence of elevated prolactin concentration on epithelial cells of prostate. We compared the morphology of epithelial cells of prostate dorsal, lateral and ventral lobes and expression of androgen receptors in these cells in rats with hyperprolactinemia and in control rats. We used sexually mature male Wistar rats. The experimental rats received metoclopramide; the control group received saline in the same way. The prostate dorsal, lateral and ventral lobes were collected routinely for light and electron microscopy. The intensity of immunohistochemical reaction of androgen receptor in epithelial cells of dorsal, lateral and ventral lobes was evaluated by measure of optical density with computer image analysis. The light and electron (transmission and scanning) microscopes were used for morphological observations. RESULTS: In experimental rats twofold increase in prolactin and twofold decrease in testosterone found. In experimental group the expression of androgen receptor was lower in columnar epithelial cells of dorsal and ventral lobes but higher in lateral one. We observed morphological abnormalities in columnar epithelial cells of lateral and dorsal lobes. The columnar epithelial cells of ventral lobes didn't show any morphological changes in hyperprolactinemia.

The presence and role of progesterone receptor in the ovaries of postmenopausal women who have not applied hormone replacement therapy.

At present, not much is known about progesterone receptor (PR) expression and localization in postmenopausal women ovaries. In the ovaries of reproductive age women, PR is localized in internal theca and granulosa cells, corpus luteum, ovary surface epithelium (OSE) and in stroma. PR expression depends on the serum concentration of progesterone, estrogen, gonadotropin and androgen. The goal of the conducted studies was to examine PR localization and expression in the ovaries of postmenopausal women who have not applied hormone replacement therapy so far. Also, the correlation was examined between PR expression and localization in the ovaries, steroid and gonadotropin hormone serum concentrations, and influence of the time from the last menstruation. The material came from 50 postmenopausal women who had their ovaries removed due to non-neoplastic diseases. The women were divided into 3 groups (A, B, C) depending on the time from the last menstruation. The follitropin (FSH), luteotropin (LH), estradiol (E2), testosterone (T), androstendione (A) and dehydroepiandrosterone sulphate (DHEAS) concentrations in blood plasma were measured. Monoclonal mouse anti-human PR antibody was used for immunohistochemical detection (examination involved 50 postmenopausal ovaries). Between particular groups, E2 serum concentrations did not differ, but FSH, LH, T, A, DHEAS serum concentrations were significantly different. Immunohistochemical nuclear localization of PR in postmenopausal women ovaries was observed. PR expression was similar in all three groups (A, B, C). PR expression was observed in OSE nuclei and invaginations cysts deriving from the isolation of invaginated epithelium and metaplastic columnar epithelium and in stroma. In the ovaries of postmenopausal women who have not applied hormone replacement therapy so far, PR was detected in all three groups. Its expression did not depend on the time from menopause and was similar in all examined groups. FSH, LH, T, A, DHEAS serum concentrations did not influence PR expression.

[Influence of dihydrotestosterone deficit on treatment of prostatic diseases regarding to contemporary methods of prostatic hypertrophy treatments]. / Wplyw deficytu dihydrotestosteronu na leczenie schorze prostaty na te wspólczesnych metod farmakologicznego leczenia przerostu tego gruczolu.

In the prostate the enzyme 5alpha-reductase converts testosterone into more active form--dihydrotestosterone (DHT). This hormone strongly influences prostate function and takes part in its pathology Since the connection between androgens and pathology of this gland has been proved, pharmacological inhibition of conversion became one of the therapy strategies both for benign prostate hyperplasia and prostate cancer. Last decade has brought numerous, long term clinical trials which involved numerous men being administered finasteride and other 5alpha-reductase inhibitors in bening prostate hypertrophy (BPH) treatment and prostate cancer (PCa) prevention. The results confirmed main assumptions, however revealed complex androgens and other factors' activity overlapping with the effect of therapy on prostate disease.

The expression of androgen receptors in the epithelial cells of the rat prostate lateral lobe in experimental hyperprolactinaemia: a morphological and immunohistochemical study.

The effect of hyperprolactinaemia on the prostate has still not been fully elucidated. The aim of the study was to estimate the influence of hyperprolactinaemia on expression of the androgen receptor (AR) in rat epithelial cells of the prostate lateral lobe and on the morphology of these cells. Studies were performed on sexually mature male Wistar rats. To provoke hyperprolactinaemia rats received i.p. metoclopramid (MCP). For light and electron microscopy the lateral lobes were obtained routinely. The intensity of the immunohistochemical reaction of AR (expression of AR) in the epithelial cells of the prostate lateral lobe was assessed by optical density measurements with the help of computer image analysis. Ultrastructural observations of the epithelial cells of the lateral lobe were carried out by means of transmission and scanning electron microscopes. The results showed a more than twofold increase in prolactin (PRL) concentration in the serum, but a twofold decrease in testosterone (T). The intensity of the immunohistochemical reaction of AR in the epithelial cells of the lateral lobe in the experimental group was higher than in the control group. We noted changes in the morphology of the epithelial cells of the prostate lateral lobe in the experimental group.