Kazeto Yukinori, Place Allen R, Trant John M
Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, MD 21202, USA.
Aquat Toxicol. 2004 Jul 30;69(1):25-34. doi: 10.1016/j.aquatox.2004.04.008.
Cytochrome P450 aromatase (CYP19) is the key steroidogenic enzyme responsible for conversion of androgens to estrogens which play a critical role in developmental sex differentiation and adult reproductive cycles in vertebrates. To evaluate the potential roles of endocrine disrupting chemicals (EDC) on reproductive physiology of fish, the influence of multiple classes of EDC on the transcript abundance of two CYP19 isoforms, CYP19A1 and A2, were investigated in zebrafish juveniles. The pharmaceutical, clofibrate, and the pesticide, atrazine, did not influence the expression of either CYP19 gene. Estrogenic compounds, nonylphenol (NP) and a pharmaceutical estrogen, ethinylestradiol (EE), strongly enhanced the expression of CYP19A2 gene in dose-dependent manner. Exposure to benzo[a]pyrene (BaP) significantly increased CYP19A2 transcript abundance. Furthermore, BaP when co-treated with EE partially suppressed EE-induced upregulation of CYP19A2. In contrast, the expression of CYP19A1 was basically resistant to EDC treatment although EE at high concentration (1-100 nM) downregulated its expression. These findings suggest that multiple classes of EDC may potentially perturb developmental and reproductive physiology in fish through differential transcriptional modulation of the CYP19 genes with the most evident disruption in neural tissue.
细胞色素P450芳香化酶（CYP19）是关键的类固醇生成酶，负责将雄激素转化为雌激素，这在脊椎动物的发育性性别分化和成年生殖周期中起着关键作用。为了评估内分泌干扰化学物质（EDC）对鱼类生殖生理学的潜在作用，研究了多种类型的EDC对斑马鱼幼鱼中两种CYP19亚型CYP19A1和A2转录本丰度的影响。药物氯贝丁酯和农药阿特拉津均未影响任一CYP19基因的表达。雌激素化合物壬基酚（NP）和药物雌激素乙炔雌二醇（EE）以剂量依赖的方式强烈增强了CYP19A2基因的表达。暴露于苯并[a]芘（BaP）显著增加了CYP19A2转录本的丰度。此外，BaP与EE共同处理时，部分抑制了EE诱导的CYP19A2上调。相比之下，CYP19A1的表达对EDC处理基本具有抗性，尽管高浓度（1 - 100 nM）的EE会下调其表达。这些发现表明，多种类型的EDC可能通过对CYP19基因的差异转录调控，潜在地干扰鱼类的发育和生殖生理学，其中神经组织中的干扰最为明显。
