Stressor: 4

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

17beta-Estradiol

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as  Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help
User term DTXID Preferred name Casrn jchem_inchi_key indigo_inchi_key
Estradiol 17B DTXSID0020573 17beta-Estradiol 50-28-2 VOXZDWNPVJITMN-ZBRFXRBCSA-N VOXZDWNPVJITMN-ZBRFXRBCSA-N

AOP Evidence

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help

Event Evidence

This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor. More help
Binding to estrogen receptor (ER)-α in immune cells

There is no evidence text for this event.

Induction of GATA3 expression

Expression of GATA3 was induced in CD4+T cells treated with E2 at a concentration of 10-9 M (272.4 pg/mL) for 12-16 hours (Lambert KC. 2005).  GATA3 expression has potential to induced IL-4 production in CD4+T cell.  In contrast, expression of T-bet was decreased, which means E2 skew the immune system from a Th1 to a Th2 profile (Lambert KC. 2005).

Increase of Th2 cells producing IL-4

In vitro, the addition of E2 significantly increased IL-4 secretion from ERα-replete CD4+T cells, while this effect was abrogated in ERα-deficient CD4+T cells. (Lambert KC. 2005).

Increase of anti-DNA antibody from autoreactive B cell

BPA as well as E2 and diethylstilbestrol (DES) enhanced anti-Br-RBC autoantibody production by B1 cells in vivo.  IgM production by B1 cells in the presence of ED was more prominent on aged BWF1 mice developing lupus nephritis. (Yurino H. 2004). 

To examine a direct effect of endocrine disruptors on IgM antibody production by B1 or B2 cells, B1 cells were prepared from peritoneal cells and B2 cells from spleen, B1 or B2 cells were cultured in the presence of endocrine disruptors (E2: 100 nM, DES: 100 nM, BPA: 1 μM) for 4 days (Yurino H. 2004). 

Direct exposure of PBMCs from SLE patients to E2 induces secretion of anti-dsDNA antibodies and enhances the secretion of Igs, in particular IgG (Kanda N. 1999).

In both (NZB×NZW) F1 and MRL/lpr mice, estrogen treatment exacerbates the lupus disease, with augmented levels of autoantibodies against dsDNA and phospholipids as well as formation of circulating immune complexes (Grimaldi CM. 2002, Peeva E. 2000).

Hybridomas generated from E2-treated mice express high-affinity, unmutated anti-DNA antibodies, indicating that naı¨ve B cells that are normally deleted or anergized are rescued from tolerance induction (Bynoe MS. 2000).  E2 treatment resulted in a rise in anti-DNA serum titers and in Ig deposition in renal glomeruli (Bynoe MS. 2000).

Exacerbation of systemic lupus erythematosus (SLE)

The NZB/W F1 mouse is the oldest classical model of lupus generated by the F1 hybrid between the NZB and NZW strains.  In both NZB/W F1 and MRL/lpr mice, estrogen treatment exacerbates the lupus disease (Grimaldi CM. 2002, Peeva E. 2000).  In postmenopausal women there was an increase in number of mild flares in women receiving estrogen supplementation suggesting that the addition of estrogen to a low estrogen state enhances flare rate (Buyon JP. 1998).

Stressor Info

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help
Chemical/Category Description
To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Chemical/Category Description”  section on the page. More help
Characterization of Exposure
To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “Characterization of Exposure”  section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.”  Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page.  The new text should appear under the “References” section on the page. More help