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Effects of Fadrozole, Ketoconazole, and 17β-trenbolone on Ex Vivo Steroidogenesis in the Fathead Minnow
Citation:
CAVALLIN, J. E., N. D. MUELLER, E. J. DURHAN, K. M. JENSEN, M. D. KAHL, E. A. MAKYNEN, D. MARTINOVIC, D. L. VILLENEUVE, AND G. T. ANKLEY. Effects of Fadrozole, Ketoconazole, and 17β-trenbolone on Ex Vivo Steroidogenesis in the Fathead Minnow. Presented at Midwest Chapter of the Society of Environmental Toxicology and Chemistry and The Northland Chapter of the Society of Toxicology Meeting, Duluth, MN, March 31 - April 02, 2008.
Impact/Purpose:
To document research results.
Description:
A variety of endocrine-disrupting chemicals have the ability to disrupt steroidogenesis through interaction with the hypothalamic-pituitary-gonadal (HPG) axis. We examined the effects of the competitive aromatase inhibitor fadrozole (0, 3, and 30 g/L), the cytochrome P450 enzyme inhibitor ketoconazole (0, 40, 400 g/L), and the androgen receptor agonist 17β-trenbolone (0, 33, and 470 ng/L) on fathead minnow (Pimephales promelas) steroidogenesis using 3 separate 16-day experiments. In each experiment, fish were chemically-exposed for 8 d, then held for an additional 8 d without chemical exposure to examine recovery. To determine the effect each chemical had on steroidogenesis, we measured ex vivo production of testosterone (T) and 17β-estradiol (E2) by gonad tissue collected after 1, 2, 4, 8, 9, 10, 12, and 16 d, using radioimmunoassays (RIAs). Fadrozole had no effect on T production in males, but increased T production in females. Fadrozole-exposed females had a concentration-dependent decrease in E2 production over the first 8 days and a higher rate of E2 production post-exposure, suggesting compensation. Ketoconazole caused a decrease in male T and female T and E2 production. Male and female T production appeared to recover during post-exposure. Trenbolone caused an initial reduction in male T and female T and E2 production, followed by recovery during the post-exposure period. Overall, the ex vivo steroid production results are consistent with the modes of action of fadrozole, ketoconazole, and trenbolone. The results from this study aid our understanding of direct and indirect effects of endocrine-disrupting chemicals on steroidogenesis.