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Temporal Evaluation of Effects of a Model 3B-Hydroxysteroid Dehydrogenase Inhibitor on Endocrine Function in the Fathead Minnow
Citation:
ANKLEY, G. T., J. E. CAVALLIN, E. J. DURHAN, K. M. JENSEN, M. D. KAHL, E. A. MAKYNEN, D. MARTINOVIC-WEIGELT, L. WEHMAS, AND DAN VILLENEUVE. Temporal Evaluation of Effects of a Model 3B-Hydroxysteroid Dehydrogenase Inhibitor on Endocrine Function in the Fathead Minnow. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, 30(9):2094-2102, (2011).
Impact/Purpose:
This information is important to the design and interpretation of approaches for assessing the occurrence and effects of HPG-active chemicals both in the lab and field.
Description:
Inhibition of enzymes involved in the synthesis of sex steroids can substantially impact developmental and reproductive processes controlled by the hypothalmic-pituitary-gonadal (HPG) axis. A key steroidogenic enzyme that has received little attention from a toxicological perspective is 3β-hydroxysteroid dehydrogenase (3β-HSD). In these studies we exposed reproductively-active fathead minnows (Pimephales promelas) to the model 3β-HSD inhibitor trilostane at two test concentrations (300 and 1500 µg/L) over a 16-d time-course that included both 8-d exposure and 8-d recovery phases. Plasma concentrations of 17β-estradiol (E2) in females were depressed within hours of exposure to the drug, and remained decreased at the highest trilostane concentration throughout the 8-d exposure. Reductions in E2 were accompanied by decreases in plasma concentrations of the estrogen-responsive protein vitellogenin (VTG). During the recovery phase of the test, plasma E2 and VTG concentrations returned to levels comparable to controls, in the case of E2 within 1 d. Up-regulation of ovarian expression of gene products for follicle-stimulating hormone receptor (fshr), and aromatase (cyp19a1a) suggested active compensation in trilostane-exposed animals. Effects of trilostane on HPG-related endpoints in exposed males were less pronounced although, as in females, there was up-regulation of gonadal fshr. Data from these time-course studies provide insights as to direct impacts, compensatory responses, and recovery from effects associated with perturbation of a comparatively poorly-characterized enzyme/pathway critical to sex steroid synthesis. This information is important to the design and interpretation of approaches for assessing the occurrence and effects of HPG-active chemicals both in the lab and field.