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DOI10.1016/j.ygcen.2017.07.022
Rapid effects of the aromatase inhibitor fadrozole on steroid production and gene expression in the ovary of female fathead minnows (Pimephales promelas)
Schroeder, Anthony L.1; Ankley, Gerald T.2; Habib, Tanwir3; Garcia-Reyero, Natalia5; Escalon, Barbara L.5; Jensen, Kathleen M.2; Kahl, Michael D.2; Durhan, Elizabeth J.2; Makynen, Elizabeth A.2; Cavallin, Jenna E.2; Martinovic-Weigelt, Dalma4; Perkins, Edward J.5; Villeneuve, Daniel L.2
发表日期2017-10-01
ISSN0016-6480
卷号252页码:79-87
英文摘要

Cytochrome P450 aromatase catalyzes conversion of C19 androgens to C18 estrogens and is critical for normal reproduction in female vertebrates. Fadrozole is a model aromatase inhibitor that has been shown to suppress estrogen production in the ovaries of fish. However, little is known about the early impacts of aromatase inhibition on steroid production and gene expression in fish. Adult female fathead minnows (Pimephales promelas) were exposed via water to 0, 5, or 50 mu g fadrozole/L for a time-course of 0.5, 1, 2, 4, and 6 h, or 0 or 50 jig fadrozole/L for a time-course of 6, 12, and 24 h. We examined ex vivo ovarian 17 beta-estradiol (E2) and testosterone (T) production, and plasma E2 concentrations from each study. Expression profiles of genes known or hypothesized to be impacted by fadrozole including aromatase (cytochrome P450 [cyp] 19a1a), steriodogenic acute regulatory protein (star), cytochrome P450 side-chain cleavage (cyp11a), cytochrome P450 17 alpha hydroxylase/17,20 lyase (cyp17), and follicle stimulating hormone receptor (fshr) were measured in the ovaries by quantitative real-time polymerase chain reaction (QPCR). In addition, broader ovarian gene expression was examined using a 15k fathead minnow microarray. The 5 mu g/L exposure significantly reduced ex vivo E2 production by 6 h. In the 50 a treatment, ex vivo E2 production was significantly reduced after just 2 h of exposure and remained depressed at all time-points examined through 24 h. Plasma E2 concentrations were significantly reduced as early as 4 h after initiation of exposure to either 5 or 50 jig fadrozole/L and remained depressed throughout 24 h in the 50 mu g/L exposure. Ex vivo T concentrations remained unchanged throughout the time-course. Expression of transcripts involved in steroidogenesis increased within the first 24 h suggesting rapid induction of a mechanism to compensate for fadrozole inhibition of aromatase. Microarray results also showed fadrozole exposure caused concentration- and time-dependent changes in gene expression profiles in many HPG-axis pathways as early as 4 h. This study provides insights into the very rapid effects of aromatase inhibition on steroidogenic processes in fish. Published by Elsevier Inc.


英文关键词Endocrine disruption;Estrogen;Microarray;Compensation;Fish
语种英语
WOS记录号WOS:000409396400008
来源期刊GENERAL AND COMPARATIVE ENDOCRINOLOGY
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/61342
作者单位1.Univ Minnesota Twin Cities, Water Resources Ctr, 1985 Lower Buford Circle, St Paul, MN 55108 USA;
2.US EPA, Natl Hlth & Environm Effects Res Lab, Duluth, MN USA;
3.Badger Tech Serv, San Antonio, TX 78216 USA;
4.Univ St Thomas, Dept Biol, Mail OWS 390,2115 Summit Ave, St Paul, MN 55105 USA;
5.US Army, Engineer Res & Dev Ctr, Environm Lab, Vicksburg, MS 39180 USA
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Schroeder, Anthony L.,Ankley, Gerald T.,Habib, Tanwir,et al. Rapid effects of the aromatase inhibitor fadrozole on steroid production and gene expression in the ovary of female fathead minnows (Pimephales promelas)[J]. 美国环保署,2017,252:79-87.
APA Schroeder, Anthony L..,Ankley, Gerald T..,Habib, Tanwir.,Garcia-Reyero, Natalia.,Escalon, Barbara L..,...&Villeneuve, Daniel L..(2017).Rapid effects of the aromatase inhibitor fadrozole on steroid production and gene expression in the ovary of female fathead minnows (Pimephales promelas).GENERAL AND COMPARATIVE ENDOCRINOLOGY,252,79-87.
MLA Schroeder, Anthony L.,et al."Rapid effects of the aromatase inhibitor fadrozole on steroid production and gene expression in the ovary of female fathead minnows (Pimephales promelas)".GENERAL AND COMPARATIVE ENDOCRINOLOGY 252(2017):79-87.
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