Opposite Effects of ACTH and Glucocorticoids on Adrenal DNA Synthesis in Vivo

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Abstract
Administration of ACTH to rapidly growing weanling rats increases of DNA synthesis in adrenal and decreases it in liver. Dexamethasone administration decreases adrenal and liver DNA synthesis. When both hormones were administered to the same animals, liver DNA synthesis was similar to that observed with dexamethasone alone, but the DNA synthesis in adrenal was lower than that obtained with ACTH alone, yet higher than that observed with dexamethasone. Plasma levels of corticosterone were similar in animals treated with ACTH or with ACTH plus dexamethasone. Aminoglutethimide stimulated adrenal DNA synthesis but less than ACTH. This substance overcame partially the inhibitory effects of dexamethasone on liver DNA synthesis but did not in adrenal. When both ACTH and aminoglutethimide were given simultaneously, adrenal are indicated. DNA synthesis was higher than that observed with each substance alone. In all experiments in which adrenal cytosol DNA polymerase was studied, the activity varied in the same direction as DNA synthesis. Opposing effects of ACTH and glucocorticoids on adrenal DNA synthesis are indicated. The finding of a glucocorticoid effect on the adrenal is supported by the demonstration of a glucocorticoid specific binding protein in adrenal cytosol. Cycloheximide blocks the stimulatory action of ACTH on both steroidogenesis and DNA synthesis. Actinomycin D and dexamethasone, blocks only the DNA synthesis-promoting action of ACTH. This latter result suggests some differences in the metabolic pathways by which ACTH controls steroidogenesis and growth in the adrenal cell.