Kelce W R, Wilson E M
Reproductive Toxicology Division, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
J Mol Med (Berl). 1997 Mar;75(3):198-207. doi: 10.1007/s001090050104.
Industrial chemicals and environmental pollutants can disrupt reproductive development in wildlife and humans by mimicking or inhibiting the action of the gonadal steroid hormones, estradiol and testosterone. The toxicity of these so-called environmental endocrine disruptors is especially insidious during sex differentiation and development due to the crucial role of gonadal steroid hormones in regulating these processes. This review describes the mechanism of toxicity and clinical implications of a new class of environmental chemicals that inhibit androgen-mediated sex development. For several of these chemicals, including the agricultural fungicide vinclozolin and the ubiquitous and persistent 1,1,1-trichloro-2,2-bis (p-chlorophenyl)ethane metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene, the molecular mechanism of action and the adverse developmental effects on male sex differentiation have been elucidated and are used as examples. Environmental chemicals with antiandrogenic activity offer profound implications with regard to recent clinical observations that suggest an increasing incidence of human male genital tract malformations, male infertility, and female breast cancer. Finally, in light of increasing concern over the potential endocrine disrupting effects of environmental pollutants, an in vitro/in vivo investigational strategy is presented which has proved useful in identifying chemicals with antiandrogen activity and their mechanism of action.
工业化学品和环境污染物可通过模拟或抑制性腺甾体激素雌二醇和睾酮的作用，扰乱野生动物和人类的生殖发育。这些所谓的环境内分泌干扰物的毒性在性别分化和发育过程中尤其隐匿，因为性腺甾体激素在调节这些过程中起着关键作用。本综述描述了一类新型抑制雄激素介导的性发育的环境化学品的毒性机制及临床意义。对于其中几种化学品，包括农用杀菌剂乙烯菌核利以及普遍存在且持久的1,1,1-三氯-2,2-双（对氯苯基）乙烷代谢物1,1-二氯-2,2-双（对氯苯基）乙烯，其作用的分子机制以及对男性性别分化的不良发育影响已得到阐明，并用作示例。具有抗雄激素活性的环境化学品对近期临床观察结果具有深远影响，这些观察结果表明人类男性生殖道畸形、男性不育和女性乳腺癌的发病率在上升。最后，鉴于对环境污染物潜在内分泌干扰作用的关注度不断提高，本文提出了一种体外/体内研究策略，该策略已被证明有助于识别具有抗雄激素活性的化学品及其作用机制。
