Regulation of steroidogenesis and prostaglandin formation in isolated adrenocortical cells: The effects of pregnenolone and cycloheximide

The steroidogenic response to ACTH in isolated feline cortical cells was completely blocked by calcium deprivation or cycloheximide, but neither treatment markedly impaired pregnenolone-induced steroid release. While ACTH-evoked steroid release was accompanied by an increase in PGE; and PGF_2α release, a potently steroidogenic concentration of pregnenolone (3 μm) was unable to augment prostaglandin (PG) release. Cycloheximide slightly obtunded basal PGE₂ and PGF_2α, release but did not prevent the ACTH-induced increase in PG release. The findings indicate that the critical role of calcium in the steroidogenic process is associated with early events in the interaction of ACTH with the cell membrane; one of the early events includes activation of PG synthesis through a mechanism involving enzyme activation rather than de novo synthesis of new enzyme protein.