Adrenocorticotropic hormone increases specific proteins of the mitochondrial fraction that are translated inside or outside this organelle in cultured adrenal tumor cells.

In addition to its stimulatory effects on steroidogenesis, adrenocorticotropic hormone (ACTH) also has a trophic action on the adrenal cell. This is manifested in part by increases in the levels of key mitochondrial steroidogenic enzymes. The mechanism by which this trophic action of ACTH occurs has been studied in monolayer cultures of mouse adrenal cortical tumor cells. ACTH treatment of these cells stimulates the relative incorporation of amino acids into at least eight specific proteins in mitochondrial preparations. Two of these ACTH-responsive proteins are among the nine major adrenal polypeptides that fulfill the criteria of mitochondrial translation products: (i) their synthesis in intact cells is specifically resistant to inhibition by cycloheximide yet uniquely sensitive to chloramphenicol and (ii) they are synthesized in vitro by isolated mitochondria. The other six ACTH-responsive proteins are within the much larger category of mitochondrial proteins that are synthesized on cytoplasmic ribosomes. One of the proteins synthesized in the cytoplasm electrophoretically comigrates with purified beef adrenodoxin reductase and another with beef adrenodoxin. These findings indicate that ACTH regulates the synthesis (and turnover, or both) of specific mitochondrial proteins that are synthesized inside as well as outside the mitochondria of these adrenal cells.