The aryl hydrocarbon receptor pathway and sexual differentiation of neuroendocrine functions

Historically, much of the research on health effects of environmental pollutants focused on ascertaining whether compounds were carcinogenic. More recent findings show that environmental contaminants also exert insidious effects by disrupting hormone action. Of particular concern are findings that developmental exposure to dioxins, chemicals that act through the aryl hydrocarbon receptor pathway, permanently alters sexually differentiated neural functions in animal models. In this review, we focus on mechanisms through which dioxins disrupt neuroendocrine development as exemplified by effects on a brain region critical for ovulation in rodents. We also provide evidence that dysregulation of GABAergic neural development may be a general mechanism underlying a broad spectrum of effects seen after perinatal dioxin exposure.