Membrane fluidity effects of estratrienes

Estrogens have demonstrable neuroprotective effects. This fact has lead to the proposed use of estrogens for the prevention and/or treatment of Alzhei mer's disease. The exact protective mechanism estrogens provide is not full y understood. In this report, a potential non-genomic mechanism for estratr ienes involving alterations in membrane fluidity was studied. Steroids, suc h as estrogen, are known to be membrane-active and can alter the lipid pack ing. In this study we used fluorescent methodologies to address the effect of naturally occurring steroids (17 alpha and 17 beta -estradiol, testoster one, and progesterone) and new estratriene analogs on membrane fluidity usi ng liposomes and HT-22 hippocampal cells. The study's results indicate ster oids, based on the estratriene nucleus, can modulate lipid packing as evide nced by (1) decreased membrane fusion events and (2) decreased membrane flu idity. The effects on the membrane were both time and concentration depende nt. It was also demonstrated through rational design estratriene analogs ca n be synthesized with enhanced membrane effects. Finally, in a glutamate-in duced toxicity HT-22 model, we also demonstrated cellular protection with t he estratriene-based molecules and analogs. The data suggest the plethora o f cellular actions of estrogens may relate to or be influenced by membrane effects of the steroid. (C) 2001 Elsevier Science Inc.