| Since the early 1990's, cognitive influences of estrogen (E2) have been widely studied, especially in the hippocampus, one of the brain regions responsible for learning and memory. Despite substantial evidence of estrogen's neuroprotective role in animals, the issue of hormone therapy (HT) was complicated and much debate was generated when E2 was combined with progesterone (P4) for clinical use in humans. It has been hypothesized that P4 counteracts the neuroprotective effects of E2. Therefore, elucidating the interactions between these two hormones in the brain is vital. The present study examines the neural physiological effects of estrogen and progesterone on the synaptic transmission and plasticity in CA1 region of different animal models including ovariectomized rat, hormone pre-treated female rat and 3xTG Alzheimer model mice. We found that E2-induced enhancement in basal transmission was decreased by P4, but E2-induced enhancement in long-term potentiation (LTP) was unaffected by P4. In summary, these results support the hypothesis that progesterone may attenuate the estrogen-induced hyperexcitability in pyramidal cells. This study shows estrogen and progesterone at certain concentrations work against each other and may explain the conflicting data on HT. With better understanding of the interactions of E2 and P4 in the future, it may become possible to design the most efficient and successful hormonal therapies. |
