Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
Aquat Toxicol. 2011 Mar;102(1-2):31-8. doi: 10.1016/j.aquatox.2010.12.019. Epub 2011 Jan 4.
The transcriptional regulator steroidogenic factor 1 (SF-1) and the enzyme cytochrome P450 aromatase (CYP19) play a central role in modulation of a broad range of tissue-specific developmental processes associated with hormone homeostasis that includes differentiation of the central nervous system. SF-1 and CYP19 expression may be targeted by a variety of endocrine disruptive agents prevalent within the environment. In the present study, we cloned and characterized partial sequences for bullfrog (Rana catesbeiana) SF-1 and CYP19 and examined the effects of a 48h exposure to 1 and 100μg/l of the herbicide atrazine (ATZ) and its major metabolite desethylatrazine (DEA), as well as 5ng/l of the estrogenic chemical, 17α-ethynylestradiol (EE(2)), and 673ng/l of the thyroid hormone, 3,5,3'-triiodothyronine (T(3)), on SF-1 and CYP19 mRNA abundance in the brains of premetamorphic bullfrog tadpoles. Quantitative RT-PCR analysis showed an increase in CYP19 mRNA following a 48h exposure to EE(2) but not T(3) while no significant changes in SF-1 transcript levels occurred. We observed a strong positive correlation between CYP19 and SF-1 transcript abundance in the ATZ-exposed animals which was not evident with DEA- or hormone-exposed tadpoles. Our results are intriguing in light of reported behavioral changes in ATZ-exposed frogs and suggest that further research is warranted to examine the relationship and role of CYP19 and SF-1 in amphibian brain development.
转录调节因子类固醇生成因子 1(SF-1)和细胞色素 P450 芳香化酶(CYP19)在调节与激素稳态相关的广泛组织特异性发育过程中发挥着核心作用,包括中枢神经系统的分化。SF-1 和 CYP19 的表达可能受到环境中存在的各种内分泌干扰物的靶向作用。在本研究中,我们克隆和鉴定了牛蛙(Rana catesbeiana)SF-1 和 CYP19 的部分序列,并研究了暴露于 1 和 100μg/l 的除草剂莠去津(ATZ)及其主要代谢物去乙基莠去津(DEA)以及 5ng/l 的雌激素 17α-乙炔基雌二醇(EE(2))和 673ng/l 的甲状腺激素 3,5,3'-三碘甲状腺原氨酸(T(3))48 小时对处于前变态期牛蛙蝌蚪大脑中 SF-1 和 CYP19 mRNA 丰度的影响。定量 RT-PCR 分析显示,暴露于 EE(2)后 CYP19 mRNA 增加,但 T(3) 没有,而 SF-1 转录水平没有明显变化。我们观察到 ATZ 暴露动物中 CYP19 和 SF-1 转录丰度之间存在强烈的正相关,而在 DEA 或激素暴露的蝌蚪中则没有这种相关性。鉴于报道的 ATZ 暴露青蛙的行为变化,我们的结果令人关注,并表明需要进一步研究以检查 CYP19 和 SF-1 在两栖动物大脑发育中的关系和作用。