Newbold Retha R, Padilla-Banks Elizabeth, Jefferson Wendy N, Heindel Jerrold J
Developmental Endocrinology and Endocrine Disruptor Section, Laboratory of Molecular Toxicology, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Int J Androl. 2008 Apr;31(2):201-8. doi: 10.1111/j.1365-2605.2007.00858.x.
Environmental chemicals with hormone-like activity can disrupt the programming of endocrine signalling pathways that are established during perinatal life and result in adverse consequences that may not be apparent until much later in life. Increasing evidence implicates developmental exposure to environmental hormone mimics with a growing list of adverse health consequences in both males and females. Most recently, obesity has been proposed to be yet another adverse health effect of exposure to endocrine disrupting chemicals (EDCs) during critical stages of development. Obesity is quickly becoming a significant human health crisis because it is reaching epidemic proportions worldwide, and is associated with chronic illnesses such as diabetes and cardiovascular disease. In this review, we summarize the literature reporting an association of EDCs and the development of obesity, and further describe an animal model of exposure to diethylstilbestrol that has proven useful in studying mechanisms involved in abnormal programming of various oestrogen target tissues during differentiation. Together, these data suggest new targets (i.e. adipocyte differentiation and mechanisms involved in weight homeostasis) of abnormal programming by EDCs, and provide evidence that support the scientific term 'the developmental origins of adult disease'. The emerging idea of an association of EDCs and obesity expands the focus on obesity from intervention and treatment to include prevention and avoidance of these chemical modifiers.
具有类激素活性的环境化学物质会扰乱围产期建立的内分泌信号通路的编程，并导致不良后果，这些后果可能直到生命后期才会显现出来。越来越多的证据表明，在发育过程中接触环境激素类似物会给男性和女性带来越来越多的不良健康后果。最近，肥胖被认为是在发育关键阶段接触内分泌干扰化学物质（EDCs）所产生的另一种不良健康影响。肥胖正迅速成为一个重大的人类健康危机，因为它在全球范围内呈流行趋势，并且与糖尿病和心血管疾病等慢性疾病有关。在这篇综述中，我们总结了报告EDCs与肥胖发生之间关联的文献，并进一步描述了一种已被证明有助于研究分化过程中各种雌激素靶组织异常编程所涉及机制的己烯雌酚暴露动物模型。这些数据共同表明了EDCs异常编程的新靶点（即脂肪细胞分化和体重稳态所涉及的机制），并提供了支持“成人疾病的发育起源”这一科学术语的证据。EDCs与肥胖之间关联这一新兴观点将对肥胖的关注重点从干预和治疗扩大到包括预防和避免这些化学修饰物。
