EFFECTS OF CORTISONE AND ACTINOMYCIN-D UPON PYRIMIDINE NUCLEOTIDE AND RNA METABOLISM IN RAT LIVER

The effects of cortisone and actinomycin-D on the incorporation in vivo of labeled orotic acid into acid-soluble nucleotides and RNA of rat liver were studied. It was found that more than half of the stimulatory effect of cortisone on isotope incorporation into RNA was a reflection of an increased specific radioactivity of the nucleotide precursors in the acid-soluble pool. The specific activity of the acid-soluble uridine nucleotides remained a constant fraction of the elevated total acid-soluble radioactivity after cortisone treatment suggesting that the hormone may have accelerated orotate transport into the liver. Analogously, but the opposite direction, the major portion of the actinomycin-D inhibition of orotate-3H incorporation into RNA was due to an actinomycin-D-mediated diminution in the specific activity of the acid-soluble pyrimidine nucleotide pool. Pretreatment of animals with actinomycin-D resulted in complete elimination of the cortisone enhancement of radioactive precursor incorporation into RNA, whereas the hormonally enhanced incorporation of 3H-orotate into the acid-soluble fraction of liver was not inhibited suggesting that this latter consequence of hormone action was not dependent on transcriptional processes. Actinomycin-D, at levels that inhibit hormonal enzyme induction, did not markedly modify the hepatic uptake or subcellular distribution of 3H-cortisone. © 1969.