title: Use of gene expression, biochemical and metabolite profiles to enhance exposure and effects assessment of the model androgen 17β-trenbolone in fish.
abstract: The impact of exposure by water to a model androgen, 17β-trenbolone (TRB), was assessed in fathead minnows using an integrated molecular approach. This included classical measures of endocrine exposure such as impacts on testosterone (T), 17β-estradiol (E2), and vitellogenin (VTG) concentrations in plasma, as well as determination of effects on the hepatic metabolome using proton nuclear magnetic resonance spectroscopy. In addition, the rates of production of T and E2 in ovary explants were measured, as were changes in a number of ovarian gene transcripts hypothesized to be relevant to androgen exposure. A temporally intensive 16-d test design was used to assess responses both during and after the TRB exposure (i.e., depuration/recovery). This strategy revealed time-dependent responses in females (little impact was seen in the males), in which changes in T and E2 production in the ovary, as well as levels in plasma, declined rapidly (within 1 d), followed shortly by a return to control levels. Gene expression measurements revealed dynamic control of transcript levels in the ovary and suggested potential mechanisms for compensation during the exposure phase of the test. Proton nuclear magnetic resonance spectroscopy revealed a number of hepatic metabolite changes that exhibited strong time and dose dependence. Furthermore, TRB appeared to induce the hepatic metabolome of females to become more like that of males at both high test concentrations of TRB (472 ng/L) and more environmentally relevant levels (33 ng/L).
authors.affiliation: U.S. Environmental Protection Agency, Athens, Georgia, USA. ekman.drew@epa.gov
authors.forename: Drew R
authors.initials: DR
authors.lastname: Ekman
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
authors.forename: Quincy
authors.initials: Q
authors.lastname: Teng
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Ralston-Hooper
authors.forename: Dalma
authors.initials: D
authors.lastname: Martinović-Weigelt
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kahl
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Jensen
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Durhan
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Makynen
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Collette
mesh_terms: D045930:Anabolic Agents / Q000633:toxicity*; D000818:Animals; D003530:Cyprinidae / Q000235:genetics* / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D010053:Ovary / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014204:Trenbolone Acetate / Q000031:analogs & derivatives* / Q000633:toxicity*; D014819:Vitellogenins / Q000097:blood
chemical_list: D045930:Anabolic Agents; D014819:Vitellogenins; D013739:Testosterone; D004958:Estradiol; D014204:Trenbolone Acetate