Patel Monali R, Scheffler Brian E, Wang Lu, Willett Kristine L
Department of Pharmacology and Environmental Toxicology Research Program, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
Aquat Toxicol. 2006 May 10;77(3):267-78. doi: 10.1016/j.aquatox.2005.12.009. Epub 2006 Feb 3.
Cytochrome P450 aromatase (CYP19) plays an important role in steroid homoeostasis by converting androgens to estrogens. To evaluate the effects of benzo(a)pyrene (BaP), a model carcinogenic PAH and AhR ligand, on aromatase mRNA expression and enzyme activity, adult Fundulus were exposed to water-borne BaP (1 and 10 microg/L) for 15 days, and embryos were exposed to 10 microg/L for 10 days. Effects of BaP were examined by tissue, gender, and season in adults. Constitutively, the sexes did not have significantly different CYP19A2 mRNA levels, however females had higher brain aromatase activity. Female control killifish had more than 700-fold more CYP19A1 mRNA in their gonads compared to males. Within brain tissue of both sexes, there was 100-fold more CYP19A2 mRNA compared to CYP19A1. In ovary, CYP19A1 predominated by approximately 30-fold over the CYP19A2, but in testis there was relatively more CYP19A2. In embryos there was approximately 5-fold higher CYP19A2 expression. Due to high inter-individual variability, a significant effect of BaP treatment by gender, season or age was not observed for either aromatase mRNA. However, ovarian aromatase activity was significantly decreased by 10 microg/L BaP, while female brain activity was increased following winter exposure. These findings suggest that the aromatase enzyme is a potential target for disruption of fish developmental and reproductive physiology by BaP.
细胞色素P450芳香化酶（CYP19）通过将雄激素转化为雌激素，在类固醇稳态中发挥重要作用。为了评估典型致癌性多环芳烃和芳烃受体（AhR）配体苯并[a]芘（BaP）对芳香化酶mRNA表达和酶活性的影响，将成年底鳉暴露于水体中的BaP（1和10微克/升）15天，胚胎暴露于10微克/升BaP 10天。在成体中，从组织、性别和季节方面检测了BaP的影响。通常，两性的CYP19A2 mRNA水平没有显著差异，然而雌性的脑芳香化酶活性更高。雌性对照鳉鱼性腺中的CYP19A1 mRNA比雄性多700倍以上。在两性的脑组织中，CYP19A2 mRNA比CYP19A1多100倍。在卵巢中，CYP19A1比CYP19A2占主导地位，约为30倍，但在睾丸中CYP19A2相对较多。胚胎中的CYP19A2表达约高5倍。由于个体间差异较大，未观察到BaP处理在性别、季节或年龄方面对芳香化酶mRNA有显著影响。然而，10微克/升BaP使卵巢芳香化酶活性显著降低，而冬季暴露后雌性脑活性增加。这些发现表明，芳香化酶是BaP破坏鱼类发育和生殖生理的一个潜在靶点。
