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

Nongenomic effects of steroids on rat brain neurotransmitter transporters a nd receptors have been reported in several laboratories. In the present stu dy, we have investigated possible membrane effects of 17 alpha- and 17 beta -estradiol, as well as tamoxifen, by studying their interactions with synth etic 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 degr ees C. Similar effects, although less pronounced, were observed with 17 bet a-estradiol, whereas 17 alpha-estradiol had no significant effect. The DPH fluorescence anisotropy of striatum and frontal cortex membranes was decrea sed in vitro with 17 beta-estradiol or tamoxifen and also with 17 alpha-est radiol, but to a lesser extent. These results suggest a stereospecific estr adiol effect on membranes and that the effects of these compounds are not r elated to their activity on estrogen receptors. These observations support a different mechanism of action of steroids that could be implicated in the ir neuroprotective activity. (C) 1999 Elsevier Science Inc.