On the requirement for protein synthesis during corticotropin-induced stimulation of cholesterol side chain cleavage in rat adrenal mitochondrial and solubilized desmolase preparations

Abstract

Following simple homogenization, significant amounts of mitochondrial-derived, cholesterol side chain cleaving enzyme (desmolase) activity are recovered in rat adrenal 105 000 × g- supernatant fraction. Corticotropin administration enhances soluble desmolase activity, and cycloheximide potentiates this effect. The lipid droplet fraction which has no desmolase activity markedly enhances pregnenolone synthesis in the soluble desmolase preparations, presumably by supplying free cholesterol substrate. Corticotropin, particularly with cycloheximide pretreatment, enhances lipid fraction activity. Thus increased cholesterol availability may largely explain the corticotropin effect on the soluble desmolase system. Since protein synthesis is required for corticotropin activity in intact mitochondria, but not in calcium-swollen mitochondria or the soluble enzyme system, the labile protein apparently required during corticotropin action may function to overcome a “barrier” which exists only in the intact mitochondria and restrains cholesterol side chain cleavage.