API

Event: 219

Key Event Title

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Reduction, Plasma 17beta-estradiol concentrations

Short name

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Reduction, Plasma 17beta-estradiol concentrations

Key Event Component

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Process Object Action
17beta-estradiol decreased

Key Event Overview


AOPs Including This Key Event

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Stressors

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Level of Biological Organization

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Biological Organization
Individual



Taxonomic Applicability

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Term Scientific Term Evidence Link
rat Rattus norvegicus Strong NCBI
human Homo sapiens Strong NCBI
fathead minnow Pimephales promelas Strong NCBI
Fundulus heteroclitus Fundulus heteroclitus Strong NCBI

Life Stage Applicability

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Life stage Evidence
Adult Strong

Sex Applicability

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Term Evidence
Unspecific Not Specified

How This Key Event Works

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Estradiol synthesized by the gonads is transported to other tissues via blood circulation. The gonads are generally considered to be the primary source of estrogens in systemic circulation.


How It Is Measured or Detected

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Total concentrations of 17β-estradiol in plasma can be measured by radioimmunoassay (e.g., (Jensen et al. 2001)), enzyme-linked immunosorbent assay (available through many commercial vendors), or by analytical chemistry (e.g., LC/MS; Owen et al. 2014). Total steroid hormones are typically extracted from plasma or serum via liquid-liquid or solid phase extraction prior to analysis.

Given that there are numerous genes, like those coding for vertebrate vitellogenins, choriongenins, cyp19a1b, etc. which are known to be regulated by estrogen response elements, targeted qPCR or proteomic analysis of appropriate targets could also be used as an indirect measure of reduced circulating estrogen concentrations. However, further support for the specificity of the individual gene targets for estrogen-dependent regulation should be established in order to support their use.

A line of transgenic zebrafish employing green fluorescence protein under control of estrogen response elements could also be used to provide direct evidence of altered estrogen, with decreased GFP signal in estrogen responsive tissues like liver, ovary, pituitary, and brain indicating a reduction in circulating estrogens (Gorelick and Halpern 2011).


Evidence Supporting Taxonomic Applicability

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Key enzymes needed to synthesize 17β-estradiol first appear in the common ancestor of amphioxus and vertebrates (Baker 2011). Consequently, this key event is applicable to most vertebrates.


References

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  • Jensen K, Korte J, Kahl M, Pasha M, Ankley G. 2001. Aspects of basic reproductive biology and endocrinology in the fathead minnow (Pimephales promelas). Comparative Biochemistry and Physiology Part C 128: 127-141.
  • Baker ME. 2011. Origin and diversification of steroids: co-evolution of enzymes and nuclear receptors. Molecular and cellular endocrinology 334(1-2): 14-20.
  • Owen LJ, Wu FC, Keevil BG. 2014. A rapid direct assay for the routine measurement of oestradiol and oestrone by liquid chromatography tandem mass spectrometry. Ann. Clin. Biochem. 51(pt 3):360-367.
  • Gorelick DA, Halpern ME. Visualization of estrogen receptor transcriptional activation in zebrafish. Endocrinology. 2011 Jul;152(7):2690-703. doi: 10.1210/en.2010-1257. Epub 2011 May 3. PubMed PMID: 21540282