Cortisol-induced increase of tyrosine-α-ketoglutarate transaminase in the isolated perfused rat liver and its relation to ribonucleic acid synthesis

Abstract

It was shown that cortisol increases the level of tyrosine-α-ketoglutarate transaminase ( l-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) of the isolated rat liver, when perfused with diluted rat blood containing an amino acid mixture; a more striking increase was obtained in the presence of a supplementary amount of tyrosine. This enhancement of activity was blocked by inhibitors both of protein synthesis (chloramphenicol, puromycin, ethionine) and of ribonucleic acid synthesis (actinomycin D and mitomycin C). Adding [6- 14C]orotate to the perfusing blood, caused a rapid incorporation of radioactivity into nuclear ribonucleic acid to take place; cytoplasmic ribonucleic acid was poorly labelled after 30 min, but its radioactivity rose thereafter. Cortisol stimulated the labelling of both the nuclear and the cytoplasmic ribonucleic acid; moreover it induced the increase of tyrosine transaminase after a lag of about 30 min. In both cases, the effect of the hormone was prevented by actinomycin D, or by mitomycin C. It was finally found that livers perfused with cortisol have a higher nuclear ribonucleic acid polymerase (nucleosidetriphosphate: RNA nucleotidyltransferase, EC 2.7.7.6) activity than control ones. The facts that the synthesis of nuclear ribonucleic acids precedes the increase of tyrosine transaminase and also that cortisol stimulates ribonucleic acid polymerase strongly suggest that the action of the hormone can be related to an increase in the synthesis of messenger ribonucleic acid molecules for the synthesis of the enzyme.