page_title: E-SCREEN
section_title: Mechanisms of action
hierarchical_section_title: E-SCREEN / Mechanisms of action
caption_attribution_description: Schematic representation of a dimer of the ligand-binding region of estrogen receptor beta in complex with 3-(6-hydroxynaphthalen-2-yl)-2H-1,2-benzoxazol-6-one. Orientation and style made to match w:Image:ERbeta.jpg by JWSchmidt. Created with Cn3D (https://www.ncbi.nlm.nih.gov/Structure/CN3D/cn3d.shtml) and GIMP.
context_page_description: E-SCREEN is a cell proliferation assay based on the enhanced proliferation of human breast cancer cells in the presence of estrogen active substances. The E-SCREEN test is a reliable tool to easily and rapidly assess estrogenic activity of suspected xenoestrogens. This bioassay that measures estrogen-induced increase of the number of human breast cancer cell, which is biologically equivalent to the increase of mitotic activity in tissues of the genital tract, was originally developed by Soto et al.
context_section_description: The biological effects of estrogens (and xenoestrogens) are mediated through the estrogen receptor (ER). Estrogen receptors, which belong to a large superfamily of nuclear receptors, are transcription factors that induce transcription of target genes after binding to specific DNA sequences in their promoter.
  There are two isoforms (ERα and ERβ): 
  The ERα is present in the uterus, and it is thought to drive the uterotropic response, since the uteri of the ERα "knock-out" mice do not respond to the estrogen administration.
  The ERβ is present in organs such as prostate, hypothalamic nuclei and pituitary gland. It is also present, together with ERα in some human breast cancer cell lines.
  The ER mediates most of the biological effects at the level of gene regulation by interacting through its site-specific DNA and with other coregulatory proteins. The classical mechanism of activation of ERs depends on ligand binding to the nuclear hormone receptors, after which the receptors dimerize and bind to estrogen response elements (EREs) located in the promoters of estrogen-responsive genes.
  Nevertheless, basic scientific research shows that estrogens (and xenoestrogens) may also exert actions through nonnuclear steroid hormone receptors (e.g., membrane ERs), nonsteroid receptors (e.g., neurotransmitter receptors such as the serotonin receptor, dopamine receptor, norepinephrine receptor), orphan receptors (e.g., aryl hydrocarbon receptor (AhR)), enzymatic pathways involved in steroid biosynthesis and/or metabolism, and numerous other mechanisms that converge upon endocrine and reproductive systems.
caption: Estrogen receptor 2 (ERβ)
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