The dose-dependent influence of hydrocortisone on the energetics of ra
t thymocytes has been studied. Prolonged action of hydrocortisone in v
ivo (20 mu g per kg body weight for 6 days daily) and preincubation of
thymocytes with hydrocortisone (10 mu M) in vitro resulted in cytotox
icity, the complete uncoupling of oxidative phosphorylation, and a dec
rease in electron transfer in the mitochondrial respiration chain. A s
ingle injection of hydrocortisone (20 mu g/kg 72 h before sacrifice) r
esulted in the uncoupling of oxidative phosphorylation. Short-term exp
osure to hydrocortisone (20 mu g/kg 3 h before sacrifice) and also pre
incubation of thymocytes with hydrocortisone (1 mu M) stimulated elect
ron transport, including substrate oxidation, without uncoupling of ox
idative phosphorylation. Short-term exposure to hydrocortisone in vivo
inhibited respiration when glucose was used as the oxidation substrat
e and stimulated respiration in medium containing sodium pyruvate.