title: Effects of a model androgen (methyl testosterone) and a model anti-androgen (cyproterone acetate) on reproductive endocrine endpoints in a short-term adult mummichog (Fundulus heteroclitus) bioassay.
abstract: A short-term gonadal recrudescence bioassay using the mummichog (Fundulus heteroclitus) was employed to examine the consequences of environmentally relevant and pharmacological exposures (1-1000 ng/l) of the androgen, 17alpha-methyl testosterone (MT), and the anti-androgen, cyproterone acetate (CA), on reproductive endocrine endpoints. Recrudescing male (GSI = approx. 2%) and female (GSI = approx. 10%) fish were exposed to graded concentrations of MT and CA for 7 or 14 days. In the first experiment (7-day exposure), MT concentrations of 250 or 1000 ng/l decreased circulating testosterone (T) and estradiol (E(2)) in female fish, and 11-ketotestosterone (11-KT) in male fish. Plasma T, 11-KT and E(2) were decreased following CA exposure (250 and 1000 ng/l). Gonadal steroid biosynthetic capacity was also inhibited in both sexes after exposure to MT or CA, as evidenced by decreased in vitro production of T and E(2). In experiment 2 (14-day exposure), exposures to lower MT and CA concentrations (1, 10 and 100 ng/l) resulted in decreased plasma T, with females showing greater sensitivity than males. Both 11-KT and E(2) were significantly reduced beginning at 10 ng/l MT. In vitro gonadal T production was impaired at 100 ng/l MT in both males and females while 1 ng/l CA caused a significant decrease in female fish. In experiment 2, in vitro E(2) production was decreased in females at all concentrations of MT and CA, while only 100 ng/l reduced 11-KT synthesis in males. Plasma vitellogenin (Vtg) was reduced in females exposed to 1000 ng/l (experiment 1) and 100 ng/l (experiment 2) MT, while CA did not alter plasma Vtg at any concentration. This bioassay has the potential to be used to assess the possible consequences in estuarine fish of exposure to environmental anti/androgens.
authors.affiliation: Department of Biology and Canadian Rivers Institute, University of New Brunswick, Saint John, NB, Canada E2L 4L5.
authors.forename: Rainie L
authors.initials: RL
authors.lastname: Sharpe
authors.forename: Deborah L
authors.initials: DL
authors.lastname: MacLatchy
authors.forename: Simon C
authors.initials: SC
authors.lastname: Courtenay
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Van Der Kraak
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D017373:Cyproterone Acetate / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood; D005260:Female; D023781:Fundulidae / Q000378:metabolism*; D006066:Gonads / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008777:Methyltestosterone / Q000494:pharmacology*; D009509:New Brunswick; D013739:Testosterone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D014819:Vitellogenins / Q000096:biosynthesis / Q000097:blood
chemical_list: D000726:Androgen Antagonists; D014819:Vitellogenins; D013739:Testosterone; D017373:Cyproterone Acetate; D004958:Estradiol; C003600:11-ketotestosterone; D008777:Methyltestosterone