Some characteristics of adrenal steroidogenesis and their possible relationships to the action of the adrenocorticotropic hormone

The effects of adrenocorticotropic hormone (ACTH) on the biphasic time curve for rat adrenal mitochondrial pregnenolone synthesis, the ACTH sensitive step of steroidogenesis in the adrenal cortex, have been investigated. The observed curve is characterized by a relatively short primary rate followed by a longer, slower secondary rate. The administration of ACTH in vivo results in an increase in both rates; however, the percentage increase is greater for the secondary rate. An increase in the duration of the primary rate was also observed. Similar results were obtained when the complete steroidogenic sequence of reactions to form corticosterone were investigated in a cell-free system. Mitochondrial pregnenolone, both total and that present in the membranes, is increased by ACTH. These data make a model for ACTH action in which an inhibition by pregnenolone of its own synthesis is controlled by the rate of efflux of pregnenolone from the mitochondria unlikely. Addition of 20,22-dihydroxycholesterol, a precursor of corticosterone, results in a decrease in the duration of the primary rate. Furthermore, the extent of the decrease depends upon the concentration of 20,22-dihydroxycholesterol. This result suggests that possible involvement of an inhibitor on the duration of the primary rate of the observed biphasic rate curve. The bearing of these results on some models for ACTH action is discussed.