Effect of dehydroepiandrosterone and its sulfate and fatty acid ester derivatives on rat brain membranes

The effects of dehydroepiandrosterone (DHEA) as well as its sulfate and fat ty acid ester derivatives on rat brain membrane fluidity was investigated b y fluorescence depolarization of a lipid probe 1,6-diphenyl- 1,3,5-hexatrie ne and compared to its effect on phospholipid conformation investigated by Fourier transform infrared spectroscopy. In rat brain, membrane fluidity va ried rostro-caudally, the frontal cortex showing the highest fluidity compa red to the hypothalamus, hippocampus, striatum, thalamus, and hindbrain. As previously reported, it was observed that cholesteryl hemisuccinate and st earic acid rigidify striatal membrane whereas linoleic acid and L-alpha-pho sphatidylcholine increase the membrane fluidity. Striatal fluidity was incr eased in vitro with increasing concentrations of DHEA, this effect was grea ter with the DHEA fatty acid ester derivatives (DHEA-L), DHEA-undecanoate, and DHEA-stearate, whereas no effect was observed with DHEA-sulfate (DHEA-S ). In the frontal cortex only the two DHEA-L derivatives increased membrane fluidity, whereas DHEA and DHEA-S were without effect. The effect of DHEA- L on synthetic dimyristoylphosphatidylcholine-d(54) phospholipid membranes indicates a disordering effect of DHEA-undecanoate and DHEA-stearate as ref lected by increased trans-gauche isomerization of the acyl chains of the li pid. Hence, DHEA-L increase the disorder and/or fluidity of brain membranes ; interestingly, these compounds are abundant in the brain where they are g enerally considered as storage compounds that slowly release the active unc onjugated steroid hormone. (C) 1999 Elsevier Science Inc. All rights reserv ed.