Progesterone blocks estrogen neuroprotection from kainate in middle-aged female rats

The neuroprotective effects of estrogen in young adult rodents are well established. Less well understood is how estrogen neuroprotection is affected by aging and interactions with progesterone. In this study, we investigated the effects of estrogen and continuous progesterone, both alone and in combination, on hippocampal neuron survival following kainate lesion in 14-month-old female rats entering reproductive senescence. Our results show that ovariectomy-induced hormone depletion did not significantly affect the extent of kainate-induced neuron loss. Treatment of ovariectomized rats with estrogen significantly reduced neuron loss, however this effect was blocked by co-administration of continuous progesterone. Treatment of ovariectomized rats with progesterone alone did not significantly affect kainate toxicity. These results provide new insight into factors that regulate estrogen neuroprotection, which has important implications for hormone therapy in postmenopausal women.