Impacts of an anti-androgen and an androgen/anti-androgen mixture on the metabolite profile of male fathead minnow urine.
Male and female fathead minnows (Pimephales promelas, FHM) were exposed via water to 20 or 200 microg/L of cyproterone acetate (CA), a model androgen receptor (AR) antagonist. FHM were also exposed to 500 ng/L of 17beta-trenbolone (TB), a model AR agonist, and to mixtures of TB with both concentrations of CA. The urine metabolite profile (as measured by 1H NMR spectroscopy) of male FHM exposed to the high concentration of CA was markedly different from that of controls, and this difference was less for males coexposed to the associated TB+CA mixture. The exposure to TB alone had almost no impact on the male urine profile. These results suggest that male FHM urinary metabolite profiling may be useful for directly detecting effects of anti-androgens. In contrast, the urinary profile of male FHM exposed to the lower concentration of CA was not very different from that of controls, but, unexpectedly, this difference was increased when coexposed to the associated TB+CA mixture. This suggests that TB with CA at the lower concentration impacts male FHM through an interactive effect possibly unrelated, or in addition, to AR antagonism. The relative occurrence of male-like nuptial tubercles in female FHM exposed to TB and to the mixtures of TB and CA supported the metabolomics data.
Collette
Timothy W
TW
Office of Research and Development, National Exposure Research Laboratory, U.S. Environmental Protection Agency, 960 College Station Rd., Athens, Georgia 30605, USA. collette.tim@epa.gov
Teng
Quincy
Q
Jensen
Kathleen M
KM
Kahl
Michael D
MD
Makynen
Elizabeth A
EA
Durhan
Elizabeth J
EJ
Villeneuve
Daniel L
DL
Martinović-Weigelt
Dalma
D
Ankley
Gerald T
GT
Ekman
Drew R
DR
D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003530:Cyprinidae / Q000378:metabolism* / Q000652:urine*; D017373:Cyproterone Acetate / Q000008:administration & dosage / Q000494:pharmacology; D004781:Environmental Exposure / Q000032:analysis*; D004784:Environmental Monitoring; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D025341:Principal Component Analysis; D018570:Risk Assessment; D014204:Trenbolone Acetate / Q000008:administration & dosage / Q000494:pharmacology
D000726:Androgen Antagonists; D000728:Androgens; D015415:Biomarkers; D017373:Cyproterone Acetate; D014204:Trenbolone Acetate