Dehydroepiandrosterone as an inducer of mitochondrial permeability transition

This paper reports an investigation upon the effect of dehydroepiandrosterone (DHEA) on some mitochondrial membrane functions, such as electron transport, transmembrane electric gradient and calcium permeability. It was found that the hormone induced the efflux of accumulated matrix Ca2+, inhibited Site I of the respiratory chain, as well as bringing about the collapse of the transmembrane potential, and mitochondrial swelling. Taking into account that cyclosporin A (CSA) inhibited Ca2+ release and the collapse of the transmembrane potential, it is concluded that the hormone may induce the opening of a non-specific transmembrane pore. The mechanism of pore opening is ascribed to peroxidation of the membrane lipid bilayer. It should be mentioned that estrone, even at the concentration of 200 muM, failed to reproduce the behavior of dehydroepiandrosterone on mitochondrial functions. (C) 2003 Elsevier Ltd. All rights reserved.