Regulation by ACTH of steroid hormone biosynthesis in the adrenal cortex

In this article, current knowledge about the mechanism of action of ACTH will be reviewed. Emphasis will be placed on events which occur subsequent to binding of ACTH to its receptor, stimulation of adenylate cyclase, and activation of protein kinase. In the first part of the review, the acute action of ACTH will be discussed with emphasis on present hypotheses as to the roles of calcium, phospholipids, sterol carrier proteins, and a "labile protein" activator of cholesterol side-chain cleavage. The presumptive role of these factors to increase the binding of cholesterol to the mitochondrial cholesterol side-chain cleavage enzyme will be discussed in the light of the concept that such binding is the step in steroidogenesis which is activated during the acute response of the adrenal cell to ACTH. In the second part of the article, the long-term action of ACTH to increase the levels of steroidogenic enzymes will be reviewed. Recent evidence is indicative that ACTH causes induction of the synthesis of key steroidogenic enzymes present in both the mitochondria and the microsomes. This appears to result from transcription of genes specific for these various species of cytochrome P-450 and ancillary proteins, resulting in increased synthesis of specific forms of mRNA. Whereas the mitochondrial steroidogenic enzymes are synthesized on cytoplasmic polysomes as precursor forms of higher molecular weight, the microsomal proteins are synthesized as forms of similar molecular weight to the mature forms.