Effect of estradiol and tamoxifen on brain membranes: investigation by infrared and fluorescence spectroscopy

Nongenomic effects of steroids on rat brain neurotransmitter transporters and receptors have been reported in several laboratories. In the present study, we have investigated possible membrane effects of 17α- and 17β-estradiol, as well as tamoxifen, by studying their interactions with synthetic phospholipid membranes using Fourier transform infrared spectroscopy. We have also used the fluidity of rat striatal and frontal cortex membranes, as determined by fluorescence depolarization of the probe 1,6-diphenyl-1,3,5-hexatriene (DPH), to probe the effects of these drugs on membranes. Our results show that tamoxifen induces conformational disorder along the acyl chains of deuterated dimirystoylphosphatidylcholine and decreases the gel to liquid-crystalline phase transition temperature by approximately 10°C. Similar effects, although less pronounced, were observed with 17β-estradiol, whereas 17α-estradiol had no significant effect. The DPH fluorescence anisotropy of striatum and frontal cortex membranes was decreased in vitro with 17β-estradiol or tamoxifen and also with 17α-estradiol, but to a lesser extent. These results suggest a stereospecific estradiol effect on membranes and that the effects of these compounds are not related to their activity on estrogen receptors. These observations support a different mechanism of action of steroids that could be implicated in their neuroprotective activity.