Some male sex hormones, progesterone and 6-ketocholestanol counteract uncoupling effects of low concentrations of the most active protonophores

Abstract

Dihydrotestosterone (DTS), testosterone (TS), progesterone (PS) and 6-ketocholestanol (kCh) counteract uncoupling in liver mitochondria, caused by low concentrations of 3, 5-di ( tret -butyl)-4-hydroxybenzylidenemalononitrile (SF6847) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Mitochondria were treated with small amounts of these uncouplers to stimulate the State 4 respiration and to decrease the respiration-supported δΨ. Both these changes were reversed or prevented by kCh, DTS, TS and PS (recoupling effect). Excess of SF6847 or FCCP resulted in uncoupling which was no longer sensitive to the recouplers. Estrone, cortisone and epiandrosterone (a DTS isomer of very low hormonal activity) were ineffective as recouplers. The effect of recouplers was specific to mitochondria, being absent from bacterial chromatophores and planar phospholipid membrane.