Potential roles of the aryl hydrocarbon receptor in female reproductive senescence.

The transition to reproductive senescence involves changes in neuroendocrine and ovarian functions, and is accelerated by activation of the aryl hydrocarbon pathway by environmental toxicants such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD). In this article, studies which provide evidence as to the possible mechanisms by which the aryl hydrocarbon receptor (AhR) acts in this capacity (i.e. disruption of ovarian, hypothalamic or suprachiasmatic nucleus function, or any combination of these) are reviewed, along with the normal physiological changes that occur during the transition to reproductive senescence in female humans and rodents. Based on findings that the AhR is evolutionarily conserved and necessary for normal fertility, we suggest that the AhR has not only a pathological but also a physiological role in the process of aging. Studies of realistic lifelong AhR activation by dioxins on the hypothalamic-pituitary-ovarian axis and its impact on the transition to reproductive senescence in the aging female are a previously neglected area of research that warrants further consideration.