Halm S, Pounds N, Maddix S, Rand-Weaver M, Sumpter J P, Hutchinson T H, Tyler C R
Department of Biological Sciences, Brunel University, Uxbridge, UB8 3PH, Middlesex, UK.
Aquat Toxicol. 2002 Oct 30;60(3-4):285-99. doi: 10.1016/s0166-445x(02)00011-5.
Oestrogens are key regulators in sexual differentiation and development in higher vertebrates. P450 aromatase (p450arom) is the steroidogenic enzyme responsible for the synthesis of oestrogens from aromatisable androgens. Effects of endocrine disrupting chemicals on steroidogenic enzyme gene expression have received little attention so far, yet it is potentially a major pathway for sexual disruption. In this 14-day study the effects of exogenous 17beta-oestradiol (E2) at environmentally relevant concentrations were assessed on gene expression of p450aromB in the gonad and brain of maturing male and female fathead minnows (FHM). Exposure to E2 resulted in an oestrogenic response as shown by a dose-dependent induction of plasma vitellogenin (VTG) in female and male fish and a dose-dependent inhibition of testis growth. There was an effect of exposure to E2 on p450aromB mRNA expression in the gonads; E2 up-regulated p450aromB mRNA expression in the testis and ovary in a dose-response manner after 14 days of exposure. In male brain, p450aromB mRNA concentrations were significantly reduced in fish exposed to 100 and 320 ng E2/l on day 4, but on day 14 were elevated in males exposed to both 32 and 100 ng E2/l. No effects of E2 on p450aromB mRNA expression occurred in the brain of females. The results of this study show that concentrations of E2 found in the environment can have disruptive effects on key steroidogenic enzyme pathways that control sexual development in fish.
雌激素是高等脊椎动物性分化和发育的关键调节因子。细胞色素P450芳香化酶（p450arom）是一种类固醇生成酶，负责将可芳香化的雄激素合成为雌激素。内分泌干扰化学物质对类固醇生成酶基因表达的影响迄今鲜受关注，但它可能是导致性别发育异常的主要途径。在这项为期14天的研究中，评估了环境相关浓度的外源性17β-雌二醇（E2）对成熟雄性和雌性黑头呆鱼（FHM）性腺和大脑中p450aromB基因表达的影响。暴露于E2导致了雌激素反应，表现为雌性和雄性鱼血浆卵黄蛋白原（VTG）的剂量依赖性诱导以及睾丸生长的剂量依赖性抑制。暴露于E2对性腺中p450aromB mRNA表达有影响；暴露14天后，E2以剂量反应方式上调了睾丸和卵巢中p450aromB mRNA的表达。在雄性大脑中，暴露于100和320 ng E2/l的鱼在第4天时p450aromB mRNA浓度显著降低，但在第14天时，暴露于32和100 ng E2/l的雄性鱼中该浓度升高。E2对雌性大脑中p450aromB mRNA表达没有影响。这项研究的结果表明，环境中发现的E2浓度可能会对控制鱼类性别发育的关键类固醇生成酶途径产生干扰作用。
