Differences In Progesterone Receptor Expression Research Articles

Biological characteristics related to treatment effects of the levonorgestrel-releasing intrauterine system on adenomyosis-associated dysmenorrhoea

Research questionTo investigate the correlations among the biological expression of steroid receptors, fibrosis levels in adenomyotic lesions, and the treatment effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) on alleviation of dysmenorrhea. DesignIn this retrospective cohort study, 125 women with adenomyosis who underwent hysterectomy were included. The tissue samples were collected from 41 patients who had been treated by the LNG-IUS prior to surgery and these patients were further categorized into an effective group (n = 18) and a failure group (n = 23) according to their self-reported relief from dysmenorrhea after 6-month treatment. The expression levels of estrogen receptor-α (ER-α), progesterone receptor (PR), and the extent of fibrosis levels in the adenomyotic lesions were measured by immunohistochemistry and Masson's trichrome staining respectively. ResultsPatients in the failure group demonstrated lower expression levels of ER-α and PR and more pronounced fibrosis in the stroma of adenomyotic lesions compared to those in the effective group. In the glandular epithelium of lesions, ER-α expression was significantly reduced in the failure group, whereas no notable difference in PR expression was observed. Notably, the staining intensity of ER-α in the stroma of the lesions was found to have the strongest positive correlation with the degree of symptom alleviation for dysmenorrhea (r=0.47) with an area under the curve of 0.894 for prediction. ConclusionsThe findings suggest that the reduced expressions of steroid receptors in adenomyotic lesions especially ER-α in the stroma were associated with an increased likelihood of treatment failure of LNG-IUS in alleviating dysmenorrhea.

P-336 Progesterone receptor is not downregulated in the endometrial epithelial compartment of women without embryo implantation during frozen thawed embryo transfer cycles

Abstract Study question Is the mean endometrial progesterone receptor (PGR) expression in the endometrial epithelial compartment different between women with and without embryo implantation failure? Summary answer PGR expression is higher in epithelial endometrial compartment of women with embryo implantation failure, during mock hormonal endometrial preparation preceding frozen thawed embryo transfer cycles. What is known already PGR downregulation is critical for embryo implantation. Downregulation takes place during the window of implantation in the EEC, while, in stromal cells, it is highly expressed. Embryos are unable to attach to the maternal surface when PGR expression remains expressed in epithelial endometrial compartment (EEC). Limited information is available whether PGR is downregulated during hormonal endometrial preparation for frozen thawed embryo transfer cycles. Study design, size, duration In this cohort study, 47 endometrial biopsies were obtained between 2016-2017 Participants/materials, setting, methods Infertile women (n = 47) submitted to frozen thawed embryo transfer (FET) cycles had an endometrial biopsy after 5 days of intravaginal progesterone supplementation during mock hormonal endometrial preparation (HEP) preceding FET and prospectively followed until confirmation of an intrauterine pregnancy. PGR immunostaining was performed using standard immunohistochemical technique (clone BSB2 - BS2126, BIO SB). PRG expression was quantified using the histologic score (HScore, range from 0 - 4). Ethical approval was obtained from local ethical committee. Main results and the role of chance Age, body mass index, endometrial thickness, and the number of embryos transferred were not significantly different between women who became or not pregnant. PGR Hscore (mean ± SD) in EEC was significantly lower in pregnant women (1.2 ± 0.8; n = 14 ) compared to women without pregnancy (2.8 ± 0.6; n = 33 ) Student t-test p < 0.0001. The AUC was 0.90 ± 0.05 (95% CI: 0.7-1) p < 0.0001 displaying 94.2 % sensitivity and 80.4% specificity for a 1.65 PGR cut-off value. Limitations, reasons for caution This is an observational study to determine if a difference in PGR expression was identified in these cases Wider implications of the findings The mean PGR expression is abnormally higher in EEC of women with embryo implantation failure using HEP for FET cycles. The 1.65 cut-off may be used in future studies to investigate whether high PGR expression is a risk factor for failure of blastocyst implantation in HEP for FET. Trial registration number not applicable

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

The Research of Feasibility and Efficacy of Radiofrequency Ablation in Treating Uterine Fibroids.

To explore the feasibility and efficacy of radiofrequency ablation in treating uterine fibroids.Ninety patients with multiple uterine fibroids, who had undergone hysterectomy were included in the study. After the uterus was resected, the temperature of 60, 80, 100°C were adopted to ablate the in vitro fibroid with each temperature dealing with 30 patients. Simultaneously, 5 patients were included, whose in vivo fibroid were ablated with the temperature of 100°C before the fibroids were removed after laparotomy. After the fibroids were ablated, the smooth muscle in the ablated center (group A), the ablated edge (group B) and 1 cm away from the ablated edge (group C) were taken. Then, the samples were stained with hematoxylin and eosin (HE) to examine the histopathological changes, and immunohistochemistry was performed to detect the expression of estrogen receptor (ER) and progesterone receptor (PR).After radiofrequency ablation, the ablated lesions were round, toast tan, and dry on gross appearance. There were no obvious tissue carbonization and there were distinct boundary from periphery tissue. In vitro: On automated analysis, the average optical density of ER and PR in group A, B, and C was lower than the control group (P < 0.05), and which were gradually raised with the increased distance to electrode. In the same treatment group, ER optical density was gradually decreased with the increased temperature among 3 different groups. The PR optical density was decreased with the increased temperature under different temperatures in group A and group B, there was significant difference among groups (P < 0.05). But in group C, there was no difference in PR expression among the temperature of 60, 80, and 100°C (P > 0.05). In vivo: Compared with the control group, the average optical density of ER and PR were significantly different among group A, B, and C (P < 0.05), what's more, it was gradually raised with the increased distance to electrode.After radiofrequency ablation, the tissues displayed coagulative necrosis, and decreased ER and PR expression. Radiofrequency ablation may be considered a minimally invasive alternative for those women who wish to retain their reproductive potential. Eighty degree Celsius was expected to be the optimum temperature in radiofrequency ablation treatment of uterine fibroid.

Tumor biology in estrogen receptor-positive, human epidermal growth factor receptor type 2-negative breast cancer: Mind the menopausal status.

Breast cancer is not one disease, but can be categorized into four major molecular subtypes according to hormone receptor [estrogen receptor (ER) and progesterone receptor (PgR)] and human epidermal growth factor receptor type 2 (HER2) expression status. Ki67 labeling index and/or multigene assays are used to classify ER-positive, HER2-negative breast cancer into luminal A and luminal B (HER2-negative) subtypes. To date, most studies analyzing predictive or prognostic factors in ER-positive breast cancer have been performed in postmenopausal women, mainly using patients and samples in adjuvant aromatase inhibitor trials. In contrast, even the clinical roles of PgR and Ki67 have been little analyzed so far in premenopausal women. PgR is one of the estrogen-responsive genes, and it has been reported that plasma estradiol levels are related to expression levels of estrogen-responsive genes including PGR in ER-positive breast cancer. In this article, biological differences, especially differences in expression of PgR and Ki67 in ER-positive breast cancer between pre- and postmenopausal women are discussed. Clinical roles of PgR and Ki67 in ER-positive breast cancer differ between pre- and postmenopausal women. We suggest that the mechanisms of development and estrogen-dependent growth of ER-positive breast cancer might differ according to menopausal status.

Expression and cellular distribution of estrogen and progesterone receptors and the real-time proliferation of porcine cumulus cells

Although the expression of estrogen and progesterone receptors within porcine ovary and cumulus-oocyte complexes (COCs) is well recognized, still little information is known regarding expression of the progesterone receptor (PGR), PGR membrane component 1 (PGRMC1) and of estrogen-related receptors (ERRγ and ERRβ/γ) in separated cumulus cells in relation to real-time proliferation. In this study, a model of oocytes-separated cumulus cells was used to analyze the cell proliferation index and the expression PGR, PGRMC1 and of ERRγ and ERRβ/γ during 96-h cultivation in vitro using real-time quantitative PCR (qRT-PCR) and confocal microscopic observation. We found that PGR protein expression was increased at 0 h, compared with PGR protein expression after 96 h of culture (P < 0.001). The expression of PGRMC1, ERRγ and ERRβ/γ was unchanged. After using qRT-PCR we did not found statistical differences in expression of PGR, PGRMC1, ERRγ and ERRβ/γ during 96 h of cumulus cells in vitro culture (IVC). We supposed that the differential expression of the PGR protein at 0 h and after 96 h is related to a time-dependent down-regulation, which may activate a negative feedback. The distribution of PGR, PGRMC1 proteins may be linked with the translocation of receptors to the cytoplasm after the membrane binding of respective agonists and intra-cytoplasmic signal transduction. Furthermore, cumulus cells analyzed at 0 h were characterized by decreased proliferation index, whereas those after 96 h of culture revealed a significant increase of proliferation index, which may be associated with differentiation/luteinization of these cells during real-time proliferation.

Role of progesterone receptor expression and proliferative activity in predicting the recurrence of meningioma

Introduction A putative role for progesterone in the growth of meningioma has been suggested. The aim of this study was to attest the role of progesterone receptor (PR) in predicting the biological behavior of meningioma. Material and methods The study included 30 cases of meningioma, 15 (50%) recurrent and 15 (50%) non-recurrent. The immunohistochemical expression of PR was studied. Cell kinetic using the Ki67/MIB-1 labelling index (LI) was evaluated and correlated to PR expression. Results PR expression was significantly more common in benign meningioma (BM) than atypical meningioma (AM) and malignant meningioma (MM). The mean Ki-67/MIB-1 LI was significantly highest in MM, high in AM and lowest in BM. In PR-negative meningioma, the mean Ki-67/MIB-1 LI was significantly higher compared with PR-positive meningioma. In the recurrent group, PR was frequently immunonegative and the mean Ki-67/MIB-1 LI was higher than that in the non-recurrent group. The difference in PR expression between non-recurrent and recurrent cases was significant only in BM. The difference in Ki-67/ MIB-1 LI was significant only when recurrent meningioma was compared with non-recurrent tumor, irrespective of the grade. Conclusion BM expresses PR more than AM and MM. The absence of this expression in BM implies a likely risk for recurrence. Ki-67/MIB-1 LI is valuable to predict tumor grade and the overall risk of recurrence. However, it must be interpreted with caution in BM.

Role of progesterone receptor expression and proliferative activity in predicting the recurrence of meningioma

Introduction A putative role for progesterone in the growth of meningioma has been suggested. The aim of this study was to attest the role of progesterone receptor (PR) in predicting the biological behavior of meningioma. Material and methods The study included 30 cases of meningioma, 15 (50%) recurrent and 15 (50%) non-recurrent. The immunohistochemical expression of PR was studied. Cell kinetic using the Ki67/MIB-1 labelling index (LI) was evaluated and correlated to PR expression. Results PR expression was significantly more common in benign meningioma (BM) than atypical meningioma (AM) and malignant meningioma (MM). The mean Ki-67/MIB-1 LI was significantly highest in MM, high in AM and lowest in BM. In PR-negative meningioma, the mean Ki-67/MIB-1 LI was significantly higher compared with PR-positive meningioma. In the recurrent group, PR was frequently immunonegative and the mean Ki-67/MIB-1 LI was higher than that in the non-recurrent group. The difference in PR expression between non-recurrent and recurrent cases was significant only in BM. The difference in Ki-67/ MIB-1 LI was significant only when recurrent meningioma was compared with non-recurrent tumor, irrespective of the grade. Conclusion BM expresses PR more than AM and MM. The absence of this expression in BM implies a likely risk for recurrence. Ki-67/MIB-1 LI is valuable to predict tumor grade and the overall risk of recurrence. However, it must be interpreted with caution in BM.

Pathological characteristics of BRCA-associated breast cancers in Hispanics

The immunophenotype of BRCA-associated breast cancer has been studied in predominantly non-Hispanic whites (NHW). We evaluated the pathological characteristics of BRCA-associated invasive breast cancer in Hispanics. A case-control study was conducted on breast cancers from Hispanic and NHW women who enrolled in an IRB-approved registry and underwent BRCA gene analysis. BRCA negative controls (41 Hispanic, 39 NHW) were matched on age and ethnicity to BRCA positive cases (39 Hispanic, 35 NHW). A tissue array was constructed to characterize the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 and p53 by immunohistochemistry. Mean age at diagnosis was 37.1 years (range 24-59) for Hispanics (80% with Mexican ancestry) and 40.1 years (range 21-63) for NHW (P = 0.03). Hispanic BRCA1 cases were more likely than BRCA negative controls to have tumors that were ER-negative (P < 0.001) and PR-negative (P = 0.001), had higher levels of Ki-67 (P = 0.001) and p53 expression, and lower levels of HER2 overexpression. When stratified by genes, there were no significant differences in expression of ER, Ki-67, HER2, and p53 by ethnicity among mutation carriers. However, a significantly higher proportion of BRCA-positive Hispanics had PR-negative tumors compared to BRCA-positive NHW (80 vs. 57%, OR = 2.9, 95% CI 1.0-8.1, P = 0.04). Hispanic BRCA-associated breast cancers were found to have the unique immunophenotype associated with BRCA mutations; however, there was a trend toward a difference in PR expression among Hispanic BRCA1 and BRCA2 cases. Additional research on the molecular mechanisms involved in the loss of PR in this population is warranted as it could have important implications for the treatment and prevention of breast cancer in Hispanics.

Effects of hormonally active agents on steroid hormone receptor expression and cell proliferation in the myometrium of ovariectomized macaques.

Hormone replacement therapy and selective estrogen receptor modulators have been controversial treatment options for postmenopausal women because of their potential health benefits and/or risks. In this study, we determine the effects of the hormonally active compounds, conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE + MPA, and tamoxifen (TAM) on the myometrium of ovariectomized macaques. Immunoexpression of estrogen receptor-α (ERα), progesterone receptor (PR), and Ki-67 in the myometrium is assessed. We found no significant difference in ERα myometrial expression in the CEE, MPA, and CEE + MPA treatment groups, but there was a significant decrease in expression in animals administered TAM versus controls. Conjugated equine estrogen-, TAM-, and CEE + MPA-treated animals had significantly increased expression of PR in myometrial cells and there was no difference in PR expression in cells from MPA-treated animals versus control animals. Myometrial cell proliferation did not significantly differ between the controls and any of the treatment groups, although normalized Ki-67 values were somewhat higher in the CEE and TAM groups. These data suggest that ERα and PR expression in the myometrium is influenced by treatment with hormonally active agents.

MARINE MICROALGAE EFFECTS ON ENDOMETRIAL EXPRESSION OF KEY MOLECULES IN PREGNANT DAIRY COWS

Feeding fish meal, high in omega-3 long chain polyunsaturated fatty acids (PUFA) has been shown to inhibit uterine secretion of series 2 prostaglandins and improve pregnancy rates. The objectives of the current study were to evaluate the effects of two sources of long chain omega-3 PUFA supplements, fish oil and marine microalgae, on the expression of key receptors and the prostaglandin H synthase-2 enzyme in bovine endometrium at the time of pregnancy recognition. Within a week of calving, lactating Holstein cows (n=12) were assigned to one of three supplements: hydrogenated plant oil (control), rumen-protected fish oil (PFO) or rumen-protected marine microalgae (PMA) high in docosahexanoic acid (DHA; C22:6, n-3). Diets were isolipidic and isonitrogenous, and were fed for four months. Circulating omega-3 PUFA concentrations were 5.96, 6.80, and 7.53% of total plasma fatty acids in control, PFO- and PMA-supplemented cows, respectively, after four months of supplementation. The PMA-supplemented cows had higher plasma DHA levels (0.72% ± 0.03, P<0.01) than PFO-supplemented cows (0.33% ± 0.02, P<0.01), which had higher levels than control animals (0.082% ± 0.005, P<0.01). Upon confirmation of pregnancy at day 17, uterine tissues were collected for analysis of relative expression and localization of progesterone receptor (PR), estrogen receptor-alpha (ERalpha), oxytocin receptor (OTR), peroxisome proliferator-activated receptor-delta (PPARdelta) and the enzyme prostaglandin H synthase-2 (PGHS-2). Cows fed either PFO or PMA showed stronger reactivity with PR antibodies in the deep glandular epithelium than those supplemented with the control (P≥0.05). Treatment differences in PR expression in other endometrial compartments were not significant, and western blotting failed to detect differences in overall PR expression (P>0.10). There was a tendency for stronger ERalpha antibody reactivity in the adluminal stroma in cows fed PMA (P<0.10), although western blotting of whole endometrial extracts indicated a trend for reduced ERalpha expression in PMA- versus PFOsupplemented animals (P<0.10). Immunohistochemistry did not indicate treatment effects on OTR, PPARdelta or PGHS-2 localization (P>0.10). However, relative protein levels of PGHS-2 were higher in cows supplemented with PFO or PMA in comparison to the control (P≥0.05), and PPARdelta expression was higher in PFO- than control- supplemented cows (P≥0.05). The results confirm the importance of source of omega-3 long chain PUFA in supplements for dairy cows. Marine microalgae are an alternative source of omega-3 PUFA that affect reproduction through different pathways than those of traditional fish-based supplements. (poster)

Regulation of sex differences in progesterone receptor expression in the medial preoptic nucleus of postnatal rats.

The medial preoptic nucleus (MPN) of the rat, an excellent model for understanding the mechanisms involved in sexual differentiation, is highly sensitive to gonadal hormones during both pre- and post-natal life. Progesterone receptor (PR) expression is sexually dimorphic in the prenatal MPN. Males have significantly higher levels of PR-immunoreactivity (PRir) than females from approximately embryonic day 19 through at least the day of birth, suggesting that PR may play a role in sexual differentiation. Because the MPN is still sensitive to steroid hormones postnatally, the present study investigated PR expression in the MPN of males and females after birth using immunocytochemistry. Results indicate that a sex difference in PR expression persists until at least postnatal day (P) 28. However, females begin to express PR around P10. Because oestradiol regulates PR expression in the adult brain, this study also examined the influence of gonadal hormones on PR expression in the neonatal male and female MPN. Castration on the day of birth significantly reduced levels of PRir in the MPN by 24 h following surgery. Ovariectomy on P4, before the onset of ovarian steroidogenesis, prevented the induction of PR expression in the female MPN, observed in controls by P13. In both sexes, the presence of PRir in the MPN is dependent on gonadal hormone exposure. These findings suggest that differences in steroid secretion by the neonatal male and female gonads are responsible for producing sex differences in the level of PR expression in the postnatal MPN.

Sex differences in progesterone receptor expression: a potential mechanism for estradiol-mediated sexual differentiation.

The differential exposure of males and females to testosterone (T) and its metabolite estradiol (E) contributes to the development of sex differences in the brain. However, the mechanisms by which T and E permanently alter neural development remain virtually unknown. Two regions of the rat preoptic area, the anteroventral periventricular nucleus (AVPv) and the medial preoptic nucleus (MPN), are sexually dimorphic and serve as models for studying the hormonal mechanisms of sexual differentiation. Around birth, these regions express dramatically higher levels of progesterone receptor immunoreactivity (PRir) in males than they do in females. The present study examined the possibility that sexually dimorphic induction of PR expression in these two regions constitutes a potential mechanism of E-mediated sexual differentiation. Prenatal exposure to either T propionate or the synthetic estrogen, diethylstilbestrol, but not dihydrotestosterone propionate, significantly increased PRir levels in the MPN and AVPv of fetal females compared with controls. Prenatal exposure to the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, significantly reduced PRir in the MPN and AVPv of fetal males, whereas the androgen receptor antagonist flutamide had no effect. This suggests that aromatization of T into E is crucial for the sex difference in PR expression in the MPN and AVPv during development.

Decreased progesterone receptor expression in the intermediate trophoblastic cells of spontaneous abortions

Objective: To determine whether there are differences in the expression of progesterone receptor (PR) in intermediate trophoblastic cells of pregnancies ending in either spontaneous abortion (SAB) or elective abortion. Design: Immunohistochemical identification of PR in intermediate trophoblastic cells. Setting: Academic medical center. Patient(s): Subjects were 86 patients who either underwent first trimester SAB or elective abortion. Intervention(s): All SAB and elective abortion specimens were serially sectioned and immunohistochemically stained for PR and for melanoma cell adhesion molecule. Melanoma cell adhesion molecule immunohistochemical staining was used as a sensitive and specific marker to identify intermediate trophoblastic cells on the adjacent tissue section. Main Outcome Measure(s): The PR staining of intermediate trophoblastic cells by semiquantitative immunostaining score. Result(s): The PR expression in intermediate trophoblastic cells was significantly greater in elective abortion specimens than in SAB specimens. When controlling for estimated gestational age, the difference in PR expression was even greater. Conclusion(s): The quantity of PR in intermediate trophoblastic cells is significantly less in SAB when compared to elective abortion pregnancies. Although it is unknown whether this is a primary or secondary event, this information may be an important finding in attempting to characterize both the molecular etiology of implantation and the molecular pathophysiology of SAB.

The expression of the proliferation marker Ki-67 and oestrogen and progesterone receptors in the proximal and distal fallopian tube

Significant epithelial proliferation is identified more frequently in the fallopian tube in patients with ovarian tumours than in control patients. More extensive sampling of the fallopian tube is also associated with a more frequent identification of epithelial proliferation.We compared cellular proliferation at either end of the fallopian tube as detected with an antiserum to the Ki-67 protein. Variations in oestrogen and progesterone receptor proteins were also examined. Proliferative activity as expressed by the Ki-67 protein, and oestrogen receptor expression was greater in the proximal fallopian tube and progesterone receptor expression was greater in the distal fallopian tube. Only the difference in progesterone receptor expression was statistically significant (P =0.0431). This study indicates that variations in Ki-67, oestrogen and progesterone receptor protein expression occur at different sites in the fallopian tube. This should be taken into account when planning studies of epithelial cell proliferation in the fallopian tube in the future.

Regulation of Estrogen Receptor and Progesterone Receptor Messenger Ribonucleic Acid by Estrogen in the Brain of the Whiptail Lizard (Cnemidophorus uniparens)

Receptive behavior in females vertebrates is controlled by hormones, principally estrogen, secreted by the ovary. Estrogen influences behavior by interacting with a specific estrogen binding protein, or receptor, located in target cells in certain hypothalamic nuclei. To better understand the molecular mechanisms involved in the control of receptive behavior in whiptail lizards, we investigated the effects of exogenous estrogen on the regulation of estrogen receptor and progesterone receptor expression in several regions of the brains of Cnemidophorus uniparens. First we determined a dosage of 17 beta-estradiol 3-benzoate (0.5 micrograms) which reliably induced receptive behavior in ovariectomized C. uniparens. Then using in situ hybridization, we examined the effects of that dosage on the expression of estrogen receptor and progesterone receptor mRNA in the brain 24 h after injection. Estrogen treatment resulted in a significant up-regulation of estrogen receptor mRNA expression in the ventromedial nucleus of the hypothalamus and torus semicircularis, down-regulation of estrogen receptor mRNA expression in the lateral septum, and no change in the periventricular nuclei of the hypothalamus, the periventricular nucleus of the preoptic area, and the dorsal hypothalamus. The same dosage resulted in increased progesterone receptor mRNA expression in the ventromedial nucleus of the hypothalamus and the periventricular nucleus of the preoptic area; no significant changes in progesterone receptor mRNA expression were observed in the periventricular nuclei of the hypothalamus or the torus semicircularis, although the differences in progesterone receptor expression in the torus semicircularis approached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)