Bigsby R, Chapin R E, Daston G P, Davis B J, Gorski J, Gray L E, Howdeshell K L, Zoeller R T, vom Saal F S
Indiana University School of Medicine, Indianapolis, Indiana, USA.
Environ Health Perspect. 1999 Aug;107 Suppl 4(Suppl 4):613-8. doi: 10.1289/ehp.99107s4613.
The major concerns with endocrine disruptors in the environment are based mostly on effects that have been observed on the developing embryo and fetus. The focus of the present manuscript is on disruption of three hormonal systems: estrogens, androgens, and thyroid hormones. These three hormonal systems have been well characterized with regard to their roles in normal development, and their actions during development are known to be perturbed by endocrine-disrupting chemicals. During development, organs are especially sensitive to low concentrations of the sex steroids and thyroid hormones. Changes induced by exposure to these hormones during development are often irreversible, in contrast with the reversible changes induced by transient hormone exposure in the adult. Although it is known that there are differences in embryonic/fetal/neonatal versus adult endocrine responses, minimal experimental information is available to aid in characterizing the risk of endocrine disruptors with regard to a number of issues. Issues discussed here include the hypothesis of greater sensitivity of embryos/fetuses to endocrine disruptors, irreversible consequences of exposure before maturation of homeostatic systems and during periods of genetic imprinting, and quantitative information related to the shape of the dose-response curve for specific developmental phenomena.
环境中内分泌干扰物的主要问题大多基于在发育中的胚胎和胎儿身上观察到的影响。本手稿的重点是三种激素系统的干扰:雌激素、雄激素和甲状腺激素。这三种激素系统在正常发育中的作用已得到充分表征,并且已知它们在发育过程中的作用会受到内分泌干扰化学物质的干扰。在发育过程中,器官对低浓度的性类固醇和甲状腺激素特别敏感。与成年期短暂激素暴露引起的可逆变化相比,发育过程中接触这些激素引起的变化通常是不可逆的。虽然已知胚胎/胎儿/新生儿与成人的内分泌反应存在差异,但关于一些问题的内分泌干扰物风险特征的实验信息极少。这里讨论的问题包括胚胎/胎儿对内分泌干扰物更敏感的假设、稳态系统成熟之前和基因印记期间暴露的不可逆后果,以及与特定发育现象的剂量反应曲线形状相关的定量信息。