scholarly journals Thermodynamic Dissection of Estrogen Receptor–Promoter Interactions Reveals That Steroid Receptors Differentially Partition Their Self-Association and Promoter Binding Energetics

Biochemistry ◽  
2012 ◽  
Vol 51 (3) ◽  
pp. 739-749 ◽  
Author(s):  
Amie D. Moody ◽  
Michael T. Miura ◽  
Keith D. Connaghan ◽  
David L. Bain
Keyword(s):  
Estrogen Receptor ◽  
Steroid Receptors ◽  
Binding Energetics ◽  
Self Association ◽  
Estrogen Receptor Promoter

scholarly journals An Immunohistochemical Study on the Expression of Sex Steroid Receptors in Canine Mammary Tumors

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Leena Rajathy Port Louis ◽  
Khub Chandra Varshney ◽  
Madhavan Gopalakrishnan Nair
Keyword(s):  
Estrogen Receptor ◽  
Epithelial Cells ◽  
Estrogen Receptor Alpha ◽  
Malignant Tumors ◽  
Steroid Receptors ◽  
Estrogen Receptor Beta ◽  
Smooth Muscles ◽  
Mammary Tumors ◽  
Benign Tumors ◽  
Canine Mammary Tumors

Steroid hormones are found to play a major role in the genesis and progression of mammary tumors. The aim of this study was to immunohistochemically detect the presence of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and progesterone receptor (PR) and also to study the association between these markers in 29 cases of benign (11) and malignant (18) canine mammary tumors. ERα immunostaining was noticed in only one case of carcinosarcoma specifically in the nuclei of epithelial and a few myoepithelial cells. ERβ immunostaining was noticed in the nuclei and cytoplasm of epithelial cells and smooth muscles lining the blood vessels. Immunoexpression of ERβ was 82% in benign tumors and 78% in malignant tumors. PR immunostaining was expressed in the nuclei of epithelial cells in both benign and malignant tumors. Among the 15 PR+ cases, 6 (55%) were of benign type, and 9 (50%) were of malignant type. The most common group of hormone receptor was the ERα−/PR+/ERβ+ (46%) in benign tumors and ERα−/PR−/ERβ+ (38%) in malignant tumors. Although there was no significant association between ERα and PR with ERβ, the findings indicated that ERβ was consistently expressed in both benign and malignant tumors, irrespective of ERα and PR status.

Enzyme-linked immunochemical measurement of estrogen receptor in gynecologic tumors, and an overview of steroid receptors in ovarian carcinoma.

1986 ◽  
Vol 32 (10) ◽  
pp. 1836-1843 ◽  
Author(s):  
J A Holt ◽  
J Bolanos
Keyword(s):  
Estrogen Receptor ◽  
Ovarian Carcinoma ◽  
Steroid Receptors ◽  
Unknown Origin ◽  
Strong Correlations ◽  
Breast Carcinomas ◽  
Ovarian Carcinomas ◽  
Discernible Effect ◽  
Gynecologic Tumors ◽  
Receptor Assays

Abstract We tested whether a newly available enzyme-linked immunoassay (EIA) validly measures estrogen receptor (ER) in gynecologic tumors. We first documented that ER so measured agreed with results by established radioligand-based assays [dextran-coated charcoal (DCC) and hydroxylapatite (HAP)] for in-house breast carcinomas and for proficiency testing specimens. Then, for gynecologic tumors, we found strong correlations between results for ER as measured by the two methods; e.g., for 27 ovarian carcinomas, r greater than or equal to 0.86. The same was true for ER measured in nine specimens of ovarian carcinoma from women who had undergone chemotherapy: r greater than or equal to 0.94. Radioinert estradiol or serum had no discernible effect on EIA measurements of ER, whereas our DCC assay was rendered uninterpretable. Evidently the EIA validly measures ER in steroidogenic tissues, including ovarian, and also in breast and uterine carcinomas. Clinical management of the latter is now based in part on results of steroid receptor assays. For ovarian carcinomas, ER assay can be helpful for determining the probable primary site of adenocarcinomas of unknown origin, and it is providing a rational basis for development of new diagnostic and therapeutic strategies.

Preparation of cytosol for steroid receptor determinations with the Beckman "Airfuge".

1979 ◽  
Vol 25 (4) ◽  
pp. 622-625 ◽  
Author(s):  
P H Heidemann ◽  
J L Wittliff
Keyword(s):  
Estrogen Receptor ◽  
Sucrose Gradient ◽  
Clinical Laboratory ◽  
Steroid Receptors ◽  
Gradient Centrifugation ◽  
Steroid Receptor ◽  
Sucrose Gradient Centrifugation ◽  
Target Organs ◽  
Estrogen Binding

Abstract Preparation of cytosols from several estrogen target organs was compared, with use of the Beckman Airfuge and a preparative ultracentrifuge. The specific estrogen-binding capacities of cytosols prepared with these instruments were indistinguishable. Similarly, the sedimentation profiles of estrogen-receptor species as determined by sucrose gradient centrifugation were identical. We conclude that the Airfuge provides a rapid, accurate, and inexpensive means of preparing cytosols for measurements of steroid receptors in the clinical laboratory.

scholarly journals Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

Reproduction ◽  
2015 ◽  
Vol 149 (6) ◽  
pp. 645-655 ◽  
Author(s):  
Oscar E Rivera ◽  
Jorgelina Varayoud ◽  
Horacio A Rodríguez ◽  
Clarisa G Santamaría ◽  
Verónica L Bosquiazzo ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mrna Expression ◽  
Estrogen Receptor Alpha ◽  
Ovarian Function ◽  
Steroid Receptors ◽  
Ovarian Response ◽  
Serum Levels ◽  
Lower Number ◽  
Expression Levels ◽  
Mrna Expression Levels

Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 μg/kg per day, BPA0.5: 0.5 μg/kg per day) from PND1 to PND14. We determined: i) follicular growth, ii) circulating levels of 17β-estradiol (E2), iii) steroid receptors (estrogen receptor alpha, estrogen receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15, BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA showed an impaired ovarian response to oFSH with a lower number of follicles ≥2 mm in diameter together with a lower number of atretic follicles and no increase in E2 serum levels in response to oFSH treatment. In addition, AR induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and BMPR1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These alterations may be the pathophysiological basis of subfertility syndrome in adulthood.

scholarly journals Recent insights into the origins of adrenal and sex steroid receptors

2002 ◽  
Vol 28 (3) ◽  
pp. 149-152 ◽  
Author(s):  
ME Baker
Keyword(s):  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Gene Transcription ◽  
Steroid Receptors ◽  
Alternative Hypothesis ◽  
Steroid Receptor ◽  
Sex Steroid ◽  
Sex Steroid Receptors ◽  
Receptor Phylogeny ◽  
Corticoid Receptor

The recent cloning by Thornton (2001) of estrogen, progesterone and corticoid receptors from lamprey provides important insights into the early evolution of adrenal and sex steroid receptors and an opportunity to elucidate the ancient steroids that regulated gene transcription. Inclusion of lamprey sequences in a steroid receptor phylogeny indicates that the estrogen receptor is the most ancient of these receptors, followed by the progesterone receptor and the corticoid receptor. Thornton proposed that estradiol was the earliest of the steroids to activate a steroid receptor. An alternative hypothesis is that a steroid in the Delta(5) pathway activated the ancestral estrogen receptor.

scholarly journals Transrepression of the estrogen receptor promoter by calcitriol in human breast cancer cells via two negative vitamin D response elements

2013 ◽  
Vol 20 (4) ◽  
pp. 565-577 ◽  
Author(s):  
Srilatha Swami ◽  
Aruna V Krishnan ◽  
Lihong Peng ◽  
Johan Lundqvist ◽  
David Feldman
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Estrogen Receptor ◽  
Promoter Sequence ◽  
Estrogen Receptor Α ◽  
Mobility Shift ◽  
Response Elements ◽  
Dihydroxyvitamin D ◽  
Mobility Shift Assay ◽  
Estrogen Receptor Promoter

Calcitriol (1,25-dihydroxyvitamin D3), the hormonally active metabolite of vitamin D, exerts its anti-proliferative activity in breast cancer (BCa) cells by multiple mechanisms including the downregulation of the expression of estrogen receptor α (ER). We analyzed an ∼3.5 kb ER promoter sequence and demonstrated the presence of two potential negative vitamin D response elements (nVDREs), a newly identified putative nVDRE upstream at −2488 to −2473 bp (distal nVDRE) and a previously published sequence (proximal nVDRE) at −94 to −70 bp proximal to the P1 start site. Transactivation analysis using ER promoter deletion constructs and heterologous promoter–reporter constructs revealed that both nVDREs functioned to mediate calcitriol transrepression. In the electrophoretic mobility shift assay, the vitamin D receptor (VDR) showed strong binding to both nVDREs in the presence of calcitriol, and the chromatin immunoprecipitation assay demonstrated the recruitment of the VDR to the distal nVDRE site. Mutations in the 5′ hexameric DNA sequence of the distal nVDRE resulted in the loss of calcitriol-mediated transrepression and the inhibition of protein–DNA complex formation, demonstrating the importance of these nucleotides in VDR DNA binding and transrepression. A putative nuclear factor-Y (NFY) binding site, identified within the distal nVDRE, led to the findings that NFY bound to the distal nVDRE site interfered with the binding of the VDR at the site and reduced calcitriol-mediated transrepression. In conclusion, the ER promoter region contains two negative VDREs that act in concert to bind to the VDR and both nVDREs are required for the maximal inhibition of ER expression by calcitriol. The suppression of ER expression and estrogen-mediated signaling by calcitriol in BCa cells suggests that vitamin D may be useful in the treatment of ER+ BCa.

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