期刊
MARINE ENVIRONMENTAL RESEARCH
卷 66, 期 1, 页码 113-115出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.marenvres.2008.02.072
关键词
gene expression profiling; ketoconazole; steroidogenesis
Ketoconazole is a fungicidal drug that inhibits function of cytochrome P450s in the synthesis of steroids. To examine if inhibition of P450 function affects gene expression in a dynamic manner, we conducted in vitro exposures of ovary tissue from fathead minnows (Pimephales promelas) to 0.5 pM ketoconazole to investigate effects on steroid production and gene expression over time. Expression of four key steroiclogenesis genes was examined at 1, 6, and 12 h of exposure. 11 P- and 200-hydroxysteroid clehydrogenases were down regulated at I h and Cytochrome P450 17 was down-regulated at 12 h, consistent with the absence of steroid production. In contrast, cytochrome P450 19A was up-regulated at 6 h, indicating feedback regulation. Microarray analysis of 12 h exposures indicated enrichment of biological processes involved in neurotransmitter secretion, lymphocyte cell activation, sodium ion transport, and embryonic development. These data suggest that, with the exception of cytochrome P450 19A, these steroid metabolic genes are regulated in a feed forward manner and that the effects of ketoconazole may be broader than anticipated based on the mechanism of action alone. Published by Elsevier Ltd.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据