Effect of adrenocorticotrophin on intracellular cholesterol transport.

Abstract

The rate of side-chain cleavage of cholesterol by mitochondria derived from mouse adrenal tumour cells was measured. Incubation of the cells in the presence of adrenocorticotrophin (ACTH) for periods of up to 1 h was without effect on the subsequent side-chain cleavage by mitochondria. However, if the cells were incubated in the presence of aminoglutethimide phosphate (0·76 mmol/l), addition of ACTH (final concentration 86 u./l) to the medium containing the cells increased the subsequent rate of side-chain cleavage by the isolated mitochondria. This response reached a maximum after incubation of cells with ACTH for 2 h and decayed when the isolated mitochondria were left at 0 °C, although a significant difference was still apparent after 120 min. Similar stimulation of mitochondrial side-chain cleavage by ACTH was observed when the reaction was inhibited by anaerobiosis instead of aminoglutethimide phosphate. Addition of dibutyryl cyclic AMP, at final concentrations greater than 10−5 mol/l, to cells during incubation with aminoglutethimide phosphate (0·76 mmol/l) also stimulated the conversion of cholesterol to pregnenolone by the mitochondria. Provided the adrenal tumour cells were incubated with aminoglutethimide, or anaerobically, the mean cholesterol content of the inner mitochondrial membrane was significantly higher (P < 0·01) when ACTH was included in the incubation medium than when it was not. It is concluded that ACTH increases the movement of cholesterol to the mitochondrial membrane which contains the side-chain cleavage enzyme system and that part of this cholesterol is used for the enhanced conversion of cholesterol to pregnenolone brought about by ACTH.