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ACTH has both short-term (acute) and long-term (chronic) effects to regulate steroid hormone biosynthesis in the adrenal cortex. The acute action of ACTH involves the mobilization of cholesterol and its binding to cytochrome P-450scc. The long-term action of ACTH involves the regulation of synthesis of the various enzymes involved in steroidogenesis. Evidence is presented that cholesterol may have a role to play in this regulatory process as it does in the short-term action of ACTH, consistent with the concept that substrates of specific forms of cytochrome P-450 are frequently able to regulate the synthesis of these specific forms.