Non-estrogenic effects of endocrine disrupters on the central nervous system

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Alkylphenols, such as p-nonylphenol (NP) and 4-tert-octylphenol (OP), and bisphenol A (BPA) are called endocrine disrupters. We examined whether these endocrine disrupters affected progesterone receptor (PR) mRNA in the adult female rat neocortex. In one experiment, ovariectomized rats were given a subcutaneous injection of 10 mg of NP, 10 mg of OP, or 10 mg of BPA, or sesame oil alone as control. Twenty-four h after the injection, the frontal cortex, parietal cortex, and temporal cortex was collected. In a second experiment to study the time-course of the effects of BPA on PR mRNA, the ovariectomized rats were given a subcutaneous injection of 10 mg of BPA and killed 0, 6, 12, and 24 h after the injection. In addition to the frontal cortex and temporal cortex, the occipital cortex and hippocampus were also collected. Northern blotting revealed that, in the first experiment, injection of NP, OP, or BPA significantly increased PR mRNA in the frontal cortex without affecting PR mRNA in the parietal cortex. In the temporal cortex, BPA significantly decreased PR mRNA, but both NP and OP did not produce significant changes. The second experiment revealed that, injection. In the temporal cortex, PR mRNA was significantly decreased 6 h after the injection of BPA and was still significantly low 24 h after the injection. In the hippocampus, BPA induced a significant increase in PR mRNA only at 24 h after the injection. No significant change was observed in the occipital cortex. These results suggest that, even in adult rats, endocrine disrupters alter the neocortical function by affecting the PR system, although the physiological significance of PR in the affected area is not known.