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

烷基酚，如对-壬基酚(NP)和4-叔辛基苯酚(OP)，以及双酚A(BPA)被称为内分泌干扰物。我们检测了这些内分泌干扰物是否影响成年雌性大鼠大脑皮层孕激素受体(PR)的mRNA。在一项实验中，去卵巢的大鼠皮下注射10毫克的NP、10毫克的OP、10毫克的双酚A或只注射芝麻油作为对照。注射后24小时取额叶皮质、顶叶皮质和颞叶皮质。在第二个实验中，为了研究双酚A对PR mRNA影响的时程，去卵巢的大鼠皮下注射双酚A 10 mg，分别在注射后0、6、12和24小时处死。除额叶皮质和颞叶皮质外，还收集了枕叶皮质和海马区。Northern blotting显示，在第一个实验中，注射NP、OP或BPA可显著增加额叶皮质PR基因的表达，而不影响顶叶皮质的PR基因表达。在颞叶皮质，双酚A显著降低PR基因的表达，但NP和OP均无明显变化。第二个实验表明，注射。在颞叶皮质，注射双酚A后6h，PR基因的表达显著降低，在注射BPA后24h仍显著低于对照组。在海马区，BPA仅在注射后24小时才引起PR基因表达的显著增加。枕叶皮质无明显变化。这些结果表明，即使在成年大鼠中，内分泌干扰物也通过影响PR系统来改变新皮质功能，尽管PR在受影响区域的生理意义尚不清楚。

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.