Dehydroepiandrosterone and related steroids inhibit mitochondrial respiration in vitro.

1. Dehydroepiandrosterone (DHEA) inhibited mitochondrial respiratory rates in the presence of tricarboxylic acid cycle intermediates with the exception of succinate. 2. Several other steroids tested for inhibitory activity on mitochondrial state 3 rate showed inhibitory potencies ranging from 0-90%. 3. Mitochondria isolated from adrenals, heart, kidneys, brain and brown adipose tissue were also inhibited by DHEA. 4. The aspartate malate shuttle system was inhibited, but the alpha-glycerophosphate shuttle was totally insensitive to DHEA. 5. The high-amplitude swelling of mitochondria in hypotonic media was inhibited by DHEA and a few other steroids.