环境内分泌干扰物对性激素合成相关酶基因调控网络的不良影响

The effect of environmental endocrine disruptors on gene regulative networks related to steroidogenesis

环境内分泌干扰物（environmental endocrine disruptor，EED）是具有干扰机体内分泌系统的一类外源性化学物质。研究表明性激素合成相关酶基因是EED的重要靶点。性激素合成与代谢的失衡可致机体生殖障碍、性分化、性发育异常及某些癌症的发病风险增加等。其中类固醇合成急性调节蛋白、芳香化酶等是性激素合成的限速酶及关键酶，这些酶及蛋白又受一系列转录因子及信号通路的调控。基于在性激素合成中的特殊作用，这些酶、转录因子及信号通路等组成的基因调控网络与EED之间的关系备受关注。遗传背景的差异性可影响机体对EED的敏感性。该文就近年来性激素合成相关酶基因的调控以及EED对其产生的不良影响作一综述。

Environmental endocrine disruptors （EED） are pollutants of many exogenous chemicals, which have the potential to disrupt endocrine functions in exposed organisms. The enzymes increasingly involved in the steroid biosynthesis pathway are being recognized as important targets for the actions of various endocrine disrupting chemicals. Interferences with steroid biosynthesis may result in impaired reproduction, alterations in sexual differentiation, sexual development and the development of certain cancers. Aromatase （CYP19） and steroidogenic acute regulatory protein regulated by some transcriptional factors and signalling pathway are considered as the key and rate-limiting enzymes. Given their key role in the formation of steroid hormones, gene regulatory networks of enzymes related to steroidogenesis are gaining interest as molecular targets. Differences in genetic background can affect body＇s sensitivity to EED. This review will provide an overview of the enzymes involved in steroidogenesis, their cellular and molecular regulation, as well as the adverse effect of EED on them.