STRUCTURE-ACTIVITY RELATIONSHIP MODEL FOR ESTROGEN RECEPTOR LIGANDS Huihui Wu November 29,2011 Xenoestrogens are spread throughout the environment affecting our daily lives and may produce potential toxic effects on human health. The purpose of this study was to develop a mechanistically reliable model capable of identifying xenoestrogens. Our hypothesis was that there are identifiable structur...

In the present study, a previously established integrated testing strategy (ITS) for in vitro estrogenicity testing was extended with additional in vitro assays in order to broaden its sensitivity to different modes of action resulting in apparent estrogenicity, i.e., other than estrogen receptor (ER) binding. To this end, an extra set of 10 estrogenic compounds with modes of action in part dif...

Abstract Soy isoflavonoids are plant phytoestrogens available as dietary supplements and are increasingly advocated as a natural alternative to oestrogen replacement therapy. As weak oestrogen agonists/antagonists with a range of other enzymatic activities, the isoflavonoids provide a useful model to investigate the actions of endocrine disruptors. Here, the activational and organisational effe...

BACKGROUND Novel in vitro methods are being developed to identify chemicals that may interfere with estrogen receptor (ER) signaling, but the results are difficult to put into biological context because of reliance on reference chemicals established using results from other in vitro assays and because of the lack of high-quality in vivo reference data. The Organisation for Economic Co-operation...

Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ERalpha and ERbeta). In this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to me...

Understanding the root molecular and genetic causes driving complex traits is a fundamental challenge in genomics and genetics. Numerous studies have used variation in gene expression to understand complex traits, but the underlying genomic variation that contributes to these expression changes is not well understood. In this study, we developed a framework to integrate gene expression and geno...

About two thirds of all human breast cancer cases are estrogen receptor positive. The drug of first choice for these patients is tamoxifen. However, about half of the recurrences after removal of the primary tumor are or become resistant to this drug. While many mechanisms have been identified for tamoxifen resistance in the lab, at present only a few have been translated to the clinic. This pa...

Although estrogen is important in human skeletal homeostasis, the major target cell in bone is unknown. Estrogen receptors (ER) have been demonstrated in osteoblasts and bone marrow stromal cells, but their presence in osteoclasts remains controversial because completely pure preparations have not been available. We have examined expression of ER-alpha and ER-beta messenger RNA (mRNA) by RT-PCR...

Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones--particularly estrogen. The biological actions of steroid hormones are mediated by the...

Abstract Background Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with variable clinical manifestations that can affect various organs and tissues. Estrogen an important element performs vital role in the pathology of SLE. It acts on target cells through binding to estrogen receptors (ERs). This study aimed assess effect ER alpha gene polymorphism SLE activity manifestati...