Polychlorinated biphenyls (PCBs) reduce brain levels of dopamine (DA) and the number of tyrosine hydroxylase positive (TH+) neurons in the substantia nigra of exposed animals. However, these studies have all been done on male animals, and information on the effects of PCBs in females is lacking. Recent epidemiological data suggests that there are gender differences in the susceptibility to PCBs, particularly in women who were occupationally exposed in the past and are now post-menopausal. Estrogen (E2) is known o be neuroprotective and to modulate DA function, suggesting that E2 withdrawal (e.g. menopause) can increase the sensitivity to neurotoxicants like PCBs. In our study, we will determine the mechanisms whereby E2 withdrawal modulates female's susceptibility to PCB-induced effects on DA function. To accomplish this goal, we will measure DA levels, the number of TH+ neurons, and ROS formation in intact adult female, ovariectomized (OVX) and OVX +E2 PCB-exposed rats.
