Effects of Actinomycin D on ACTH-Induced Corticosteroidogenesis1

Actinomycin D was found to abolish completely the in vitro steroidogenic effect of ACTH during incubations of cow adrenal slices. The antibiotic had no effect on base line (control) corticosteroid production or on the enhanced production of corticosteroids due to addition of glucose-6-PO4, plus TPN. The inhibitory effects of actinomycin D were reversible and were evident only if the antibiotic was present during the preincubation and incubation with ACTH. In contrast to the results obtained with bovine adrenal tissue slices, actinomycin D had little or no effect on ACTH-induced corticosteroid production during incubations of rat adrenal quarters, despite inhibition of precursor incorporation into RNA. The latter, however, was not complete, and, while a role for RNA synthesis was not apparent in the rat adrenal, it could not be fully excluded. The incorporation of orotic acid-6-14C into cow adrenal (but not rat adrenal) RNA was enhanced by ACTH, and a linear relationship between orotic acid incorporation and the log of the ACTH concentration was observed. Actinomycin D inhibited orotic acid incorporation and obliterated the differences between control and ACTH-stimulated tissues. (Endocrinology78: 929, 1966)