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Neurotoxicology. 2008 May;29(3):504-19. doi: 10.1016/j.neuro.2008.02.015. Epub 2008 Mar 18.

Building a scientific framework for studying hormonal effects on behavior and on the development of the sexually dimorphic nervous system.

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Exponent Health Sciences, San Francisco, CA 94114, USA.


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.

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