You are here:
Effects of a 3β-hydroxysteroid Dehydrogenase Inhibitor, Trilostane, on the Fathead Minnow Reproductive Axis
Citation:
VILLENEUVE, D. L., L. S. Blake, J. D. Brodin, J. E. Cavallin, E. J. DURHAN, K. M. JENSEN, M. D. KAHL, E. A. MAKYNEN, D. MARTINOVIC, N. D. Mueller, AND G. T. ANKLEY. Effects of a 3β-hydroxysteroid Dehydrogenase Inhibitor, Trilostane, on the Fathead Minnow Reproductive Axis. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 104(1):113-123, (2008).
Impact/Purpose:
The objective of this study was to test the hypothesis that exposure to the model 3β-HSD inhibitor, trilostane, would adversely affect reproductive success of the fathead minnow (Pimephales promelas).
Description:
A number of environmental contaminants and plant flavonoid compounds have been shown to inhibit the activity of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD). Because 3β-HSD plays a critical role in steroid hormone synthesis, inhibition of 3β-HSD represents a potentially important mode of endocrine disruption that may cause reproductive dysfunction in fish or other vertebrates. The objective of this study was to test the hypothesis that exposure to the model 3β-HSD inhibitor, trilostane, would adversely affect reproductive success of the fathead minnow (Pimephales promelas). Results of in vitro experiments with fathead minnow ovary tissue demonstrated that trilostane inhibited 17β-estradiol (E2) production in a concentration- and time-dependent manner, and that the effect was eliminated by providing a substrate (progesterone) that does not require 3β-HSD activity for conversion to E2. Exposure of fish to trilostane caused a significant reduction in spawning frequency and cumulative egg production over the course of the 21 d test. In females, exposure to 1500 g trilostane/L reduced plasma vitellogenin concentrations, but did not cause significant histological alterations. In males, average trilostane concentrations as low as 50 g/L significantly increased testis mass and gonadal-somatic-index. Trilostane exposure did not influence the abundance of mRNA transcripts coding for 3β-HSD or other steroidogenesis-regulating proteins in males or females. As a whole, results of this study supported the hypothesis that 3β-HSD inhibition can cause reproductive dysfunction in fish, but did not yield a clear profile of responses at multiple levels of biological organization that could be used to diagnose this mode of action.