The effects of sex hormones on the expression of the clock protein PER2 in the central extended amygdala

Recently, oscillators in the oval nucleus of the bed nucleus of the stria terminalis (OV-BNST), the central nucleus of the amygdala (CEA), hippocampus (HIPP) and basolateral amygdala (BLA) of male rats have been shown to rhythmically express Period 2 (PER2), clock gene protein, with peak expression in the early evening. Little is known about these novel oscillators in females, for instance whether these regions express PER2 rhythmically with the same magnitude and phase as males or are influenced by stage of the estrus cycle remains to be determined. Female Wistar rats were sacrificed at different circadian times and days of the estrus cycle, and their brains processed for immunocytochemistry for PER2. Significant differences in the pattern of expression of PER2 in the OV-BNST and the CEA as a function of the day of the estrus cycle were found. PER2 expression peaked at different times on metestrus, and diestrus than the other two days of the cycle. In the BLA, HIPP, and suprachiasmatic nucleus, however, time of peak expression of PER2 remained constant across the estrus cycle, peaking in the early evening. In order to investigate the role of fluctuating gonadal hormones on the pattern of PER2 expression, ovariectomised females were assigned to groups based on circadian time of day. In ovariectomised females peak expression of PER2 was observed in the early evening in all areas examined. The data from this study suggests that sex hormones modulate the pattern of clock gene expression in the OV-BNST and CEA, and provide some insight into gender differences in mood disorders and disruption of circadian functioning.