Regulation of the biosynthesis of cytochromes P-450 involved in steroid hormone synthesis.

The actions of ACTH to regulate the synthesis of the various enzymes involved in steroid hormone biosynthesis have been studied using bovine adrenocortical cells in monolayer culture. ACTH causes an increase in the synthesis of both the mitochondrial and the microsomal forms of cytochrome P-450 involved in steroid hormone biosynthesis, as well as of the iron-sulfur protein involved in transferring electrons to the mitochondrial forms of cytochrome P-450, namely, adrenodoxin. This increased synthesis is reflective of an increase in translatability of mRNA species specific for these various proteins, and appears in each case to be mediated by cyclic AMP. Whereas the mitochondrial proteins are synthesized as precursors of higher molecular weight which are processed upon insertion into the mitochondria, the microsomal proteins are synthesized as species identical in molecular weight to the mature forms. In order to determine whether the action of ACTH to increase the rate of synthesis of these proteins is the result of an increase in the levels of specific mRNA species, cDNA clones complementary to these mRNA species are being isolated. These probes will also make it possible to characterize the genes encoding the steroidogenic enzymes, as well as to identify regulatory elements which control their transcription.