Dehydroepiandrosterone as an inducer of mitochondrial permeability transition

J Steroid Biochem Mol Biol. 2003 Dec;87(4-5):279-84. doi: 10.1016/j.jsbmb.2003.09.002.

Abstract

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 Ca(2+), 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 Ca(2+) 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 microM, failed to reproduce the behavior of dehydroepiandrosterone on mitochondrial functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cattle
  • Cyclosporine / pharmacology
  • Dehydroepiandrosterone / pharmacology*
  • Dose-Response Relationship, Drug
  • Estrone / pharmacology
  • Intracellular Membranes / drug effects*
  • Intracellular Membranes / metabolism
  • Ion Transport / drug effects
  • Kidney Cortex / metabolism
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondrial Swelling / drug effects
  • Oxygen Consumption / drug effects
  • Permeability / drug effects
  • Rats
  • Serum Albumin, Bovine / pharmacology
  • Succinic Acid / pharmacology
  • Thiobarbituric Acid Reactive Substances / analysis
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Thiobarbituric Acid Reactive Substances
  • Serum Albumin, Bovine
  • Estrone
  • Dehydroepiandrosterone
  • Cyclosporine
  • Succinic Acid
  • Calcium