Estrogens, apoptosis and cells of neural origin

In view of the relevant complexity of estradiol actions in the nervous syst em, 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 elici ted by E2 in the neural target cells we believe that the physiological effe cts exerted by this hormone will be more easily elucidated; in addition, we might find novel targets for drugs aimed at mimicking or blocking E2 effec ts. We here summarize preliminary results obtained in the cell line SK-ER3 appropriately engineered by us to express the ER alpha. We show that nip-2, one of the genes found to be regulated by E2, is involved in the mechanism s leading to cell death. This finding led us to investigate on estrogen eff ects on SK-ER3 apoptosis. We found that E2 has a significant anti-apoptotic activity in SK-ER3 cells. These results are in line with the recent report s from other laboratories indicating that E2 may prevent death of neural ce lls exposed to toxic stimuli. We conclude that these initial studies seem t o support the strategy of our research and underline the strength of invers e genetics in the study of the physiology of sex hormone activities.