E1 E2 metabolism v1

Feminization of male fish and the role of endocrine-active chemicals in this phenomenon has been an area of intense study for many years. Estrone (E1), a natural steroid, is found in aquatic environments sometimes at relatively high concentrations. However, E1 has been less thoroughly studied than 17β-estradiol (E2) or 17α-ethynylestradiol due in part to a relatively lower potency in metabolically-limited estrogen receptor (ER) binding/activation assays. Recent evidence suggests that in vivo biotransformation of E1 to E2 may occur in fathead minnows (Pimephales promelas) residing in environments with high concentrations of E1, such as near wastewater treatment plants. The enzymes likely responsible for this biotransformation, 17β-hydroxysteroid dehydrogenases (17βHSDs), have been well characterized in mammals but to a lesser extent in fish species. In the current study, a novel systematic analysis of amino acid sequence data from the National Center for Biotechnology Information database demonstrated that multiple 17βHSD isoforms are conserved across different fish species. Experimentally, we showed that metabolically-active hepatic cytosolic preparations from two commercially important salmonid species, rainbow trout and lake trout, biotransformed E1 to E2 to a degree sufficient to alter results of competitive ER binding assays. These results from in silico and in vitro analyses indicate E1 and biotransformation may play a significant role in the feminization of a variety of fish species in contaminated aquatic environments. This dataset is associated with the following publication: Tapper, M., R. Kolanczyk, C. LaLone, J. Denny, and G. Ankley. Conversion of estrone to 17â-Estradiol: A potential confounding factor in assessing risks of environmental estrogens to fish. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 39(10): 2028–2040, (2020).

                                            [
  "020:00"
]
                                        

                                            {
  "fn": "Mark Tapper",
  "hasEmail": "mailto:tapper.mark@epa.gov"
}
                                        

                                            [
  {
    "title": "tapper A-0p2w dataset E1 SUMMARY DATA MANUSCRIPT.xls",
    "mediaType": "application/vnd.ms-excel",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1518528/tapper%20A-0p2w%20dataset%20E1%20SUMMARY%20DATA%20MANUSCRIPT.xls"
  }
]
                                        

                                            [
  "17β-estradiol",
  "17β-hydroxysteroid dehydrogenases",
  ": metabolism",
  "estrogen receptor",
  "estrone",
  "fish"
]
                                        

                                            [
  "020:095"
]
                                        

                                            {
  "name": "U.S. EPA Office of Research and Development (ORD)",
  "subOrganizationOf": {
    "name": "U.S. Environmental Protection Agency",
    "subOrganizationOf": {
      "name": "U.S. Government"
    }
  }
}
                                        

                                            [
  "https://doi.org/10.1002/etc.4828"
]
                                        

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