Estrogens, apoptosis and cells of neural origin

In view of the relevant complexity of estradiol actions in the nervous system, we have proposed to utilize a reductionist approach and gain an insight on its role in neural cells via the identification of the genes target for this hormone. Once obtained a biochemical footprint of the responses elicited by E2 in the neural target cells we believe that the physiological effects exerted by this hormone will be more easily elucidated; in addition, we might find novel targets for drugs aimed at mimicking or blocking E2 effects. We here summarize preliminary results obtained in the cell line SK-ER3 appropriately engineered by us to express the ERalpha. We show that nip-2, one of the genes found to be regulated by E2, is involved in the mechanisms leading to cell death. This finding led us to investigate on estrogen effects on SK-ER3 apoptosis. We found that E2 has a significant anti-apoptotic activity in SKER3 cells. These results are in line with the recent reports from other laboratories indicating that E2 may prevent death of neural cells exposed to toxic stimuli. We conclude that these initial studies seem to support the strategy of our research and underline the strength of inverse genetics in the study of the physiology of sex hormone activities.