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Event Title

Plasma 17beta-estradiol concentrations, Reduction
Short name: Plasma 17beta-estradiol concentrations, Reduction

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female KE Strong
Aromatase inhibition leading to reproductive dysfunction KE Strong
Androgen receptor agonism leading to reproductive dysfunction KE Strong
Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation KE Moderate
Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription KE

Taxonomic Applicability

Name Scientific Name Evidence Links
rat Rattus sp. Strong NCBI
human Homo sapiens Strong NCBI

Level of Biological Organization

Biological Organization

How this Key Event works

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

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

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.


  • 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