Estrogen and progesterone binding by acoustic neuroma tissue

Tissue samples from 37 acoustic neuromas were assayed for estrogen and progesterone hormone receptor binding by radioimmunoassay using a dextran-coated charcoal method and Scatchard plot analysis. Twenty-one of the samples were from men, and 16 of the samples were from women. Seven of 37 samples (19%) were positive for estrogen receptor and six of 36 samples (17%) were positive for progesterone receptor. Three of 37 samples (8%) were positive for both receptors. There was no correlation of estrogen receptor positivity with the sex of the patient. These results indicate that estrogen or progesterone receptor binding activity or both are present in a small subset of acoustic tumors. Evidence is lacking, however, that binding of estrogen to the receptor results in growth changes in the tumor. The empirical use of antiestrogen treatment in acoustic neuroma does not appear to be justified at the present time.     

Estrogen receptor kinetics in benign and malignant diseases of the breast and their clinical implication

Estrogen and progesterone binding capacities in the breast tissues were determined. Unoccupied cytoplasmic estrogen receptor (ERc) levels in 19(37%) out of 52 patients with breast cancer revealed more than 30fmol/mg protein. None of tissues from the benign breast diseases contained higher unoccupied ERc than 30fmol/mg protein. There was no significant difference between the level of unoccupied ERc in the patients with fibroadenoma and that in those with mastopathy. Occupied ERc levels were significantly lower than unoccupied ERc in the breast cancer, but the difference was not observed in benign breast diseases. Occupied nuclear estrogen receptor (ERn) levels were significantly lower than unoccupied ERn only in the premenopausal patients with breast cancer, but no significant difference was observed in the patients with benign breast diseases. The level of progesterone receptor (PgR) was low in both breast cancer and benign breast diseases. Serum estradiol (E2) and progesterone (PRG) concentrations were assayed on patients with the benign breast diseases who had regular menstrual cycles. Significant negative correlations were recognized between the levels of PRG and PgR at a luteal phase, but not between E2 and unoccupied ERc. Four (33%) out of 12 patients with recurrent breast cancer responded to the endocrine therapy. In three (75%) of the four responded patients unoccupied ERc level of the cancer tissue was more than 30fmol/mg protein.     

Estrophilin immunoreactivity versus estrogen receptor binding activity in meningiomas: evidence for multiple estrogen binding sites

The existence of estrogen receptors in human meningiomas has long been a controversial issue. This may be explained, in part, by apparent heterogeneity of estrogen binding sites in meningioma tissue. In this study, estrogen receptors were determined in 58 meningiomas with an enzyme immunoassay using monoclonal antibodies against human estrogen receptor protein (estrophilin) and with a sensitive radioligand binding assay using 125I-labeled estradiol (125I-estradiol) as radioligand. Low levels of estrophilin immunoreactivity were found in tumors from 62% of patients, whereas radioligand binding activity was demonstrated in about 46% of the meningiomas examined. In eight (14%) tissue samples multiple binding sites for estradiol were observed. The immunoreactive binding sites correspond to the classical, high affinity estrogen receptors: the Kd for 125I-estradiol binding to the receptor was approximately 0.2 nM and the binding was specific for estrogens. The second, low affinity class of binding sites considerably influenced measurement of the classical receptor even at low ligand concentrations. The epidemiological and clinical data from patients with meningiomas, and the existence of specific estrogen receptors confirmed by immunochemical detection, may be important factors in a theory of oncogenesis.     

Estrogen and progesterone receptors in meningiomas

Estradiol and progesterone receptors were studied in 14 patients with meningiomas. Estrogen receptors were detected by specific monoclonal antibodies, whereas progesterone receptors were assayed by the dextran-coated charcoal method. In 9 cases the estrogen receptors were also investigated in cultured tumor cells. Positive estrogen and progesterone receptors were found in 86% of patients. The results have been compared with 11 published series of sex steroid assays in meningiomas. The different rate of positive results in most series can be explained by preoperative glucocorticoid therapy. There is no correlation between the estrogen and progesterone receptor activity, the sex and age of the patients, and the location and histological features of the meningioma. The authors suggest that assays of antiestrogen and antiprogestin drugs in cultured cells can indicate whether this estrogen and progesterone receptor activity may be of therapeutic use.     

Estrogen and progesterone receptors in meningiomas: comparison of nuclear binding, dextran-coated charcoal, and immunoperoxidase staining assays

We studied the status of estrogen (ER) and progesterone (PR) receptors in meningiomas removed from 52 patients, comparing dextran-coated charcoal (DCC), nuclear binding (NB), and immunoperoxidase (IP) assays. Each of the assays was performed independently by investigators well-experienced with these assays. The NB assay is a new assay that measures functional steroid receptors--that is, the activation of the receptor and its binding to the nucleus. The assay is very sensitive and requires a relatively small amount of tissue as compared with the DCC assay. In agreement with data from other studies. PR were detected in most meningiomas by all 3 methods: in 69% of the cases by NB, in 76% by DCC, and in 89% by IP. ER were detected in only a few cases: in 33% by NB, in 2% by DCC, and in none by the IP assay. The agreement for PR sites was 62% for all 3 assays; it was 66% between the NB and DCC assays, 67% between the NB and IP assays, and 86% between the DCC and IP assays. Of 26 cases that were positive by the DCC assay, 6 (23%) were negative by NB. The overall agreement for all three ER assays was 65%. The data suggest that the majority of meningiomas contain high-affinity receptors for progesterone, that estrogen receptors are present in only a few meningiomas, and that some of these estrogen and progesterone receptors appear to be functional.     

Effect of operative devascularization on estrogen and progesterone receptor levels in breast cancer specimens

To compare estrogen and progesterone receptor values between biopsy and mastectomy specimens, we prospectively studied 29 patients with breast cancer treated by incisional biopsy followed by mastectomy. The average tumor size was 5.4 +/- 0.5 cm and the mean age was 57.6 +/- 3.0 years. Nine patients were premenopausal and 20 were postmenopausal. Biopsies were performed without electrocautery, and tissue samples were promptly frozen and subsequently assayed for estrogen and progesterone receptor levels. After mastectomy, samples of residual tumor were excised from the biopsy site, promptly frozen, and assayed for estrogen and progesterone receptor levels. Operating time averaged 87.7 +/- 6.0 minutes. Estrogen receptor levels averaged 100.0 +/- 24.4 femtomole per mg on biopsy specimens and 29.5 +/- 8.2 fmol/mg on mastectomy specimens, representing a 70% decline (p less than 0.02). Of clinical significance is the fact that eight of 29 (27.6%) tumors changed from positive estrogen receptor values in the biopsy specimen to negative (four) and borderline (four) in the mastectomy specimens. Progesterone receptor levels were more variable, but their mean value decreased by 24.4% from 17.6 +/- 6.4 fmol/mg on biopsy samples to 13.3 +/- 4.3 fmol/mg on mastectomy samples (p, not significant). We conclude that the biopsy specimen is usually a more reliable indicator of hormonal receptor status than the mastectomy specimen and recommend that incisional or excisional biopsy specimens be taken for estrogen and progesterone receptor assays before mastectomy.     

Steroid hormone receptors in laryngeal carcinoma

The larynx has long been shown to be a target organ for androgenic steroids in both women and men, and specific androgen receptors have been determined in normal laryngeal mucosa and in laryngeal carcinoma tissue. In this study, samples from 21 primary laryngeal carcinomas, from 4 recurrent laryngeal carcinomas and from 1 cervical metastasis of laryngeal carcinoma were obtained at the time of surgery to assay specific androgen, estrogen, and progesterone receptors. Specific androgen receptors were found in 8 samples (31%). The level of receptors varied from 1.7 femtomoles (fmol) per milligram to 7.3 fmol/mg cytosol protein. Detectable levels of specific estrogen receptors were found in 18 samples (69%) and progesterone receptors in 8 of the 15 samples studied (53%). There was no apparent correspondence with donors' sex, since samples from both females and males contained all kinds of receptors. We know that antiestrogen inhibits the growth of squamous carcinoma cells lines positive for estrogen receptors in vitro and that this effect is reversible with the appropriate hormone. Thus, the relatively high percentage of estrogen and progesterone receptors found in laryngeal carcinoma tissue may open new aspects in the treatment of laryngeal carcinoma with antihormones.     

Androgen receptors in osteoblast-like cell lines

Summary Although androgens exert major effects on bone remodeling, the mechanisms by which they exert their effects remain unclear. Recently, it has become apparent that receptors for sex steroids may be present in osteoblastic cells. We have examined several cell lines with osteoblastic phenotypes to determine if specific, high affinity androgen receptors are present. Two cell lines of human origin (Saos-2 and U2-OS) and one of rat origin (UMR-106.01) were studied. Androgen binding sites were present in all cell lines. Binding affinities were high (K_D=1.6−2.5×10⁻¹⁰ M), and similar to those in classical androgen target tissues (prostate, kidney). Concentrations were greater in the human cell lines (1277 and 1605 sites/cell) than in the rodent line (74 sites/cell). In the human cell lines androgen binding was also specific and typical of androgen receptors in other tissues. Specific estrogen binding was not present in the UMR-106.01 cells, and no estrogen receptors were detectable in the human cell lines using an enzyme-linked receptor immunoassay. Specific binding for progesterone was also absent in the UMR-106.01 cells, but progesterone receptors were detected immunologically in the Saos-2 (119 sites/cell) and U2-OS (118 sites/cell) lines. These findings indicate the presence of androgen receptors that are of similar character to those in classical androgen target tissues, and suggest that the study of these cell lines may be useful in the study of the regulation of androgen effects in osteoblasts.     

Correlation between sex hormone binding and peritumoral edema in intracranial meningiomas

Estrogen and progesterone receptor binding activity was measured in 22 intracranial meningioma surgical specimens. None of the tumors was estrogen receptor-positive, whereas 19 were progesterone receptor-positive. Of these 19 patients, all demonstrated significant computed tomographic (CT) evidence of peritumoral edema. None of the 3 patients who lacked progesterone receptor binding had CT evidence of peritumoral edema (P less than 0.005). Peritumoral edema associated with intracranial meningiomas seems to be related, at least in part, to progesterone binding activity. This implicates the potential use of progesterone antagonists for the treatment of incompletely resected or recurrent meningiomas.     

Characteristics and biological role of steroid hormone receptors in neuroepithelial tumors

Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors. Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively. Only a few tumors showed estrogen or progesterone receptors. A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors. The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors. For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml). A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture. No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses. Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status. All of the cultures tested for testosterone activity were negative for androgen receptors. This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml. The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins. Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone.     

Cystosarcoma phylloides. A steroid receptor and ultrastructure analysis.

Six cases of cystosarcoma phylloides were evaluated by ultrastructure and steroid receptor analysis. Electron microscopy of the lesions supported previous reports of a heterogeneous tumor consisting of pleomorphic mesenchyme and normal or proliferative epithelium. In each case estrogen and progesterone receptor analysis indicated the presence of a nonsaturable estrogen and progesterone 4S binding protein rather than a specific steroid receptor as suggested by previous studies.     

Correlation of estrogen, progesterone, and androgen receptors in breast cancer

Breast cancer was induced in female Holtzman rats by intragastric administration of 7,12-dimethylbenz[a]antracene (DMBA). At tumor maturity, biopsies of viable tissue were obtained, frozen, and then assayed for estrogen, progesterone, and androgen receptor content. By simple linear regression analysis, progesterone receptor levels significantly correlated with both estrogen and androgen receptor levels, whereas estrogen and androgen receptor levels did not correlate with each other. Multiple regression analyses further substantiated the predictive value of the progesterone receptor for the other two hormone receptors. Knowledge of breast tumor androgen receptor levels may further enhance the value of the estrogen receptor and progesterone receptor in hormonal responsiveness. Further, the progesterone receptor may be the most sensitive of the steroid hormone receptors for selecting patients likely to respond to hormonal therapy.     

Evidence of progesterone receptors in the mucosa of the urinary bladder.

OBJECTIVE: To investigate whether progesterone receptors are present in the mucosa of the urinary bladder of continent premenopausal women compared with continent postmenopausal women. MATERIALS AND METHODS: Fifty-seven biopsies from the mucosa of the trigone and lateral wall of the urinary bladder were examined by the avidin-biotin-peroxidase immunohistochemical technique for the presence of estrogen and progesterone receptors. The specimens were obtained at cystoscopy performed to investigate hematuria in 42 patients and neoplasia in 15. The study group (n = 29) comprised non-pregnant premenopausal women in the luteal phase of their menstrual cycle and the control group (n = 28) comprised postmenopausal women. None of the subjects had urinary incontinence or was taking medication with hormones. In no case did the primary lesion involve the specimen used for laboratory analysis. RESULTS: There was positive immunostaining with estrogen in 28 patients of the study group (96.5%) and 4 (14.4%) in the control group (p<0.0001). The 28 samples of the study group also showed positive immunostaining for progesterone receptors. There was positive immunostaining with progesterone in 18 samples (64.3%) of the control group (p<0.01). Fourteen samples (50%) of the control group thus showed positive immunostaining for progesterone but no evidence of positive immunostaining with estrogen. Immunostaining for estrogen and progesterone receptors was similar in trigonal and lateral wall samples. CONCLUSION: In continent pre- and post-menopausal women, a direct progestogenic effect on the mucosa of the urinary bladder seems likely in addition to estrogen.     

Progesterone receptors regulate gallbladder motility

The increased incidence of gallstones in multiparous women may be related to hormonal effects on the gallbladder and its contractility. The occurrence of estrogen and progesterone receptors were studied in the gallbladders of three groups of female guinea pigs (normals, oophorectomized, and oophorectomized treated with estrogen + progesterone for 14 days). Gallbladder contractile response in vivo to cholecystokinin (CCK) was related to the presence of these receptors. The gallbladders from normal females showed low progesterone and estrogen binding activity (4.9 +/- 2.0 and 2.4 +/- 0.8 fmoles/mg cytosol protein). Oophorectomized females had no detectable progesterone or estrogen receptors, but after treating oophorectomized females for 14 days with estrogen + progesterone, gallbladder concentrations of progesterone receptors increased significantly to 14.7 +/- 5.9 fmoles/mg and estrogen binding activity was minimally detectable at 1.4 +/- 0.8 fmoles/mg. The gallbladder contractile response to CCK was inversely related to the concentration of progesterone receptors in the gallbladder wall. These data suggest that the gallbladder contains progesterone receptors which are susceptible to circulating hormonal conditions and which have a regulatory effect on gallbladder contractility.     

Androgen receptor binding activity in meningiomas

Analyses of androgen receptor binding activity in 54 intracranial, intraspinal, and metastatic meningiomas were performed with a specific radioligand binding technique using [3H]R 1881 as radioligand. [3H]R 5020 was used for the concurrent determination of progesterone receptor binding activity. Moderate concentrations of androgen receptors (33.4 +/- 5.4 fmol/mg protein) were detected in 35 (65%), whereas high levels of progesterone binding components (236 +/- 35 fmol/mg protein) were demonstrated in 48 (89%) tumors. The androgen receptor binding activity was positively correlated with the progesterone receptor binding activity (rs = 0.38, p less than 0.05). This relationship is suggestive of an androgen regulation of the progesterone receptor via the androgen receptor system. The presence of androgen and progesterone receptors in a large proportion of meningiomas, and the tendency for a dependence of androgen receptor and progesterone receptor binding activity on the histological subtype could have implications for tumor therapy.     

Sex steroid hormone receptors in normal and dysplastic bone disorders in children

Children with monostotic and polyostotic bone dysplasias often exhibit localized bone overgrowth. We investigated the presence of nuclear estrogen and nuclear progesterone receptors by solid-phase radioimmunoassay, immunocytochemistry, and radioligand binding in osteoblast cell cultures derived from the areas of overgrowth of membranous bone, noninvolved membranous bone, and normal membranous bone from children undergoing elective craniotomy. Membranous bone of normal children had demonstrable levels of nuclear estrogen and progesterone receptors identified by radioimmunoassay and immunocytochemical assay. Two- to threefold increased levels of these receptors (p less than 0.001 versus normals) were found in cultures derived from the involved bone of two children with monostotic fibrous dysplasia and in one patient with polyostotic dysplasia (McCune-Albright syndrome). The noninvolved bone in our patients with fibrous dysplasia exhibited nuclear sex steroid hormone receptor levels similar to those in the normal children. Radioligand binding studies demonstrated increased sex steroid hormone receptors in cultures derived from involved osteoblasts. The presence of an increased level of sex steroid hormone receptor was accompanied by increased alkaline phosphatase activity and increased production of osteocalcin in vitro compared to normal or noninvolved bone. The mechanisms by which sex steroid hormone receptor levels are increased in the ostotic dysplasias remain to be established.     

Hormone Receptor Status of Breast Cancer in the Himalayan Region of Northern India

The role of hormone receptors as a prognostic and therapeutic tool in breast cancer is widely accepted. The frequency of nonreactivity of estrogen and progesterone receptors in breast cancer patients of India is much more common than in the West. This study was conducted with the aim of analysis of steroid receptor status in breast cancer with clinico-pathological characteristics from the northern hilly state of Himachal Pradesh, India located in the region of the Western Himalayas. Fifty five consecutive patients with the diagnosis of breast cancer were included in this study. Detailed clinical and histopathologic data was recorded in all cases. Estrogen receptor and progesterone receptor status was evaluated by immunohistochemistry. Chi-square test was used for statistical analysis. On immunohistochemical staining, 34.5% cases proved to be estrogen receptor positive and 36.4% cases progesterone receptor positive. The results in the present study documented low estrogen receptor and progesterone receptor positivity in breast cancer from this region of India.     

Estrogen receptor immunoreactivity in meningiomas. Comparison with the binding activity of estrogen, progesterone, and androgen receptors

Estrogen receptor (ER) analysis was performed in 70 meningioma samples by means of two assays: an enzyme immunoassay that used monoclonal antibodies against human ER protein (estrophilin), and a sensitive radioligand binding assay that used iodine-125-labeled estradiol as the radioligand. Low levels of ER immunoreactivity were found in tumors from 51% of patients, whereas ER binding activity was demonstrated in 40% of the meningiomas examined. In eight (11%) of the tissue samples, multiple binding sites for estradiol were observed. The immunoreactive binding sites corresponded to those of the classic high-affinity ER. In ligand binding studies, however, measurement of classic ER was considerably influenced by a second low-affinity high-capacity estrogen binding component, even at low ligand concentrations. Binding activity of the progesterone receptor (PR) and androgen receptor (AR) was determined concurrently using 17 alpha-methyl-3H-promegestone (3H-R 5020) and 17 alpha-methyl-3H-trienolone (3H-R 1881), a synthetic gestagen and androgen, respectively. High concentrations of PR were detected in 53 (76%) of the tumors, whereas a moderate number of AR binding sites were demonstrated in 33 (47%) of the tumors. A positive correlation between ER immunoreactivity and AR binding activity is suggestive of estrogen regulation of AR via the ER system. The presence of gonadal steroid receptors in a large proportion of meningiomas and the tendency toward a dependence of receptor concentrations on the histological subtype of the meningioma could have implications for tumor therapy.     

Quantitative Progesterone Receptor Expression and Efficacy of Anti‐estrogen Therapy in Breast Cancer

The central role of estrogen receptor (ER) presence in predicting which breast cancer patients are likely to benefit from anti‐estrogen therapies is well‐established, but the added benefit of progesterone receptor (PR) and in particular low levels of PR is less well understood. The objective of this study was to determine the quantitative relationship between borderline levels of PR and subsequent benefit from anti‐estrogen therapy. We examined data from 447 patients, age 50 or older. ER and PR levels were quantitated by conventional ligand binding assay and Scatchard plot analysis or by enzyme‐linked immunoassay. Comparison of clinical outcome in relation with ER and PR status was calculated using Kaplan‐Meier actuarial survival analysis and the log‐rank test. Subpopulation treatment effect pattern plot (STEPP) analysis was used to explore the interaction between treatment effects and ER or PR levels for the 409 patients with ER values greater than 0. For anti‐estrogen treated patients, when the ER and PR positivity cut‐off was set at 1.0 fmole/mg protein, there was a statistically significant advantage for patients with ER+PR+ over ER+ PR? tumors for both breast cancer‐free interval (BCFI) and overall survival (OS). STEPP analysis found no overall interaction between treatment outcome (5 year survival probability) and levels of hormone receptor. However, patients with borderline PR levels did not appear to benefit from anti‐estrogen therapy. PR levels above borderline in addition to the presence of ER predicts an increased probability of benefit from anti‐estrogen therapy in breast cancer patients.     

降调节联合雌孕激素对改善PCOS患者冻融D3胚胎移植临床结局的分析

目的研究降调节联合雌孕激素替代治疗(HRT)对多囊卵巢综合征(PCOS)患者冻融胚胎移植(FET)临床结局的影响。方法回顾性分析2017年1月至2018年12月在山西省运城市中心医院生殖医学科接受FET治疗的70例PCOS患者(70个周期)的临床资料,根据子宫内膜准备方案的不同,分为降调节联合雌孕激素替代组(降调节+HRT组,32个周期)和雌孕激素替代组(HRT组,38个周期),比较分析两组患者的一般资料及妊娠结局。结果降调节+HRT组和HRT组患者的年龄、不孕年限、基础性激素水平、体重指数(BMI)、移植胚胎数等比较均无显著性差异(P>0.05)。两组的胚胎种植率、临床妊娠率、异位妊娠率、早期流产率比较亦无显著性差异(P>0.05)。降调节+HRT组的补佳乐使用时间及使用剂量、转化日E 2水平显著低于HRT组,而转化日内膜厚度及移植日内膜厚度显著高于HRT组(P均<0.05)。结论降调节联合雌孕激素替代方案用于PCOS患者FET周期的内膜准备,可以减少雌激素的使用时间和剂量,改善子宫内膜厚度,可以获得较为满意的临床结局。