Li Abby A, Baum Michael J, McIntosh Laura J, Day Mark, Liu Feng, Gray L Earl
Exponent Health Sciences, San Francisco, CA 94114, USA.
Neurotoxicology. 2008 May;29(3):504-19. doi: 10.1016/j.neuro.2008.02.015. Epub 2008 Mar 18.
There has been increasing concern that low-dose exposure to hormonally active chemicals disrupts sexual differentiation of the brain and peripheral nervous system. There also has been active drug development research on the therapeutic potential of hormone therapy on behaviors. These different research goals have in common the need to develop reliable animal models to study the effect of hormones on brain function and behaviors that are predictive of effects in humans. This paper summarizes presentations given at the June 2007 11th International Neurotoxicology Association (INA-11) meeting, which addressed these issues. Using a few examples from the bisphenol A neurobehavioral literature for illustrative purposes, Dr. Abby Li discussed some of the methodological issues that should be considered in designing developmental neurobehavioral animal studies so they can be useful for human health risk assessment. Dr. Earl Gray provided an overview of research on the role of androgens and estrogens in the development of the brain and peripheral nervous system and behavior. Based on this scientific foundation, Dr. Gray proposed a rational framework for the study of the effects of developmental exposures to chemicals on the organization of the sexually dimorphic nervous system, including specific recommendations for experimental design and statistical analyses that can increase the utility of the research for regulatory decision-making. Dr. Michael Baum and by Dr. Feng Liu presented basic research on the hormonal mechanisms underlying sexual preference and estrogenic effects of cognition, respectively. These behaviors are among those studied in adult animals following in utero exposure to hormonally active chemicals, to evaluate their potential effects on sexual differentiation of the brain. Understanding of the hormonal mechanisms of these behaviors, and of relevance to humans, is needed to develop biologically plausible hypotheses regarding the potential effects of hormonally active chemicals in humans.
人们越来越担心，低剂量接触具有激素活性的化学物质会扰乱大脑和外周神经系统的性分化。同时，针对激素疗法对行为的治疗潜力也开展了积极的药物研发研究。这些不同的研究目标都有一个共同需求，即开发可靠的动物模型来研究激素对大脑功能和行为的影响，这些影响能够预测对人类的作用。本文总结了在2007年6月第11届国际神经毒理学协会（INA - 11）会议上的发言，这些发言探讨了这些问题。艾比·李博士以双酚A神经行为学文献中的几个例子为例进行说明，讨论了在设计发育神经行为动物研究时应考虑的一些方法学问题，以便这些研究对人类健康风险评估有用。厄尔·格雷博士概述了雄激素和雌激素在大脑、外周神经系统发育及行为中的作用的研究。基于这一科学基础，格雷博士提出了一个合理的框架，用于研究发育期接触化学物质对两性异形神经系统组织的影响，包括对实验设计和统计分析的具体建议，这些建议可提高研究对监管决策的实用性。迈克尔·鲍姆博士和刘峰博士分别介绍了性偏好和认知雌激素效应背后的激素机制的基础研究。这些行为是在子宫内接触具有激素活性的化学物质的成年动物中所研究的行为之一，以评估其对大脑性分化的潜在影响。要就具有激素活性的化学物质对人类的潜在影响提出生物学上合理的假设，就需要了解这些行为的激素机制及其与人类的相关性。
