Early Effects of ACTH on Adrenal Protein Synthesis

Abstract

The sequential changes in activity of adrenal subcellular fractions for supporting incorporation of C14-amino acid into protein in a cell-free system have been followed during the first 24 hr. of in vivo ACTH administration. During the first 2-4 hr. of ACTH stimulation the incorporating activity of the 15,000 x g supernatant is decreased, and this appears to be due to a decrease in microsomal activity. The decrease in microsomal activity is accompanied by a parallel decrease in microsomal (ribosomal) RNA, suggesting that ACTH, in the doses employed, results in an early enhancement of microsomal RNA turnover. In contrast to the early decrease in microsomal activity, there is concomitantly a moderate, transient increase in soluble cell fraction activity which appears to be due to an increase in soluble transfer enzymes. Subsequent to these changes at 2-4 hr. microsomal activity and microsomal RNA increase progressively, while soluble cell fraction activity decreases transiently and then increases. The reciprocal nature of the changes in soluble cell fraction activity relative to the changes in microsomal activity and microsomal RNA may possibly reflect the existence of distribution equilibrium of the transfer enzymes between soluble cell fraction and operative ribosomal sites. Thus, some of the early changes in soluble cell fraction activity may be secondary to the ribosomal changes. Additionally, in view of the early gross inhibitory effects of ACTH on adrenal protein synthesis, it seems likely that, if the steroidogenic action of ACTH is mediated via protein synthesis, it would be via the synthesis of selected protein rather than total adrenal protein.