TEMPORAL EVALUATION OF EFFECTS OF A MODEL 3β-HYDROXYSTEROID DEHYDROGENASE INHIBITOR ON ENDOCRINE FUNCTION IN THE FATHEAD MINNOW

被引:15
作者
Ankley, Gerald T. [1 ]
Cavallin, Jenna E. [1 ]
Durhan, Elizabeth J. [1 ]
Jensen, Kathleen M. [1 ]
Kahl, Michael D. [1 ]
Makynen, Elizabeth A. [1 ]
Martinovic-Weigelt, Dalma [1 ]
Wehmas, Leah C. [1 ]
Villeneuve, Daniel L. [1 ]
机构
[1] US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Duluth, MN USA
关键词
Fathead minnow; Reproduction; Endocrine function; Toxicity mechanisms; Steroidogenesis; FOLLICLE-STIMULATING-HORMONE; PIMEPHALES-PROMELAS; MESSENGER-RNA; REPRODUCTIVE TOXICITY; STEROID BIOSYNTHESIS; ANGUILLA-JAPONICA; BREAST-CANCER; JAPANESE EEL; IN-VITRO; TRILOSTANE;
D O I
10.1002/etc.593
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). In these studies, we exposed reproductively-active fathead minnows (Pimephales promelas) to the model 3b-HSD inhibitor trilostane at two test concentrations (300 and 1,500 mu g/L) over a 16-d period that included both 8-d exposure and 8-d recovery phases. Plasma concentrations of 17 beta-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 those of 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, up-regulation of gonadal fshr was seen. 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 in both the laboratory and the field. Environ. Toxicol. Chem. 2011;30:2094-2102. (C) 2011 SETAC
引用
收藏
页码:2094 / 2102
页数:9
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